reproductive system
• in addition to a normal male reproductive tract, XY mice developed uteri and oviducts
|
Allele Symbol Allele Name Allele ID |
Amhr2tm3(cre)Bhr targeted mutation 3, Richard R Behringer MGI:3042214 |
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Summary |
45 genotypes
|
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• in addition to a normal male reproductive tract, XY mice developed uteri and oviducts
|
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• female mice become infertile after 3 to 4 months of breeding
|
• after 3 months of age, 100% of female mice have unilateral or bilateral ovarian tumors
|
• over 70% of female mice have metastic ovarian cancer by 1 year of age
|
• 100% of male mice by 7 months of age exhibit tumors in the testis
• early stage tumors appear to be sex cord stromal tumors with Sertoli and Leydig cell differentiation
|
• female mice become infertile after 3 to 4 months of breeding
|
• slight infertility, with a 16% decrease in litters per month when bred to wild-type females
|
• after 3 months of age, 100% of female mice have unilateral or bilateral ovarian tumors
|
• over 70% of female mice have metastic ovarian cancer by 1 year of age
|
• 100% of male mice by 7 months of age exhibit tumors in the testis
• early stage tumors appear to be sex cord stromal tumors with Sertoli and Leydig cell differentiation
|
• found in 50% of female mice over 9 months in age
• found in about 60% of male mice by 11 months in age
|
• after 3 months of age, 100% of female mice have unilateral or bilateral ovarian tumors
|
• over 70% of female mice have metastic ovarian cancer by 1 year of age
|
• 100% of male mice by 7 months of age exhibit tumors in the testis
• early stage tumors appear to be sex cord stromal tumors with Sertoli and Leydig cell differentiation
|
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
N |
• mutant females display normal estrous cycles and mating behavior relative to control littermates
|
• adult day-1 pregnant female mutants display reduced ovarian weights relative to age-matched control littermates
|
• unlike wild-type, mutant oviducts lack extensive coiling and appear more transparent under a dissecting microscope
• distended sac-like structures filled with clear fluid are observed at the end of the oviduct near the uterotubal junction
• oviducts of both immature and pregnant female mutants rupture easily, do not appear patent, and cannot be flushed
• mutant oviducts display a disorganized epithelial cell layer while the isthmus region is almost devoid of smooth muscle tissue
|
• both untreated and eCG+hCG-treated immature (day 25) and adult day-1 pregnant female mutants display shorter oviducts that are less than one half the length of control littermates
|
• mutant uteri appear more transparent than control uteri under a dissecting microscope
|
• both eCG+hCG-treated immature and adult pregnant female mutants exhibit reduced numbers of uterine glands relative to control littermates
|
• both eCG+hCG-treated immature and adult pregnant female mutants display a thinner myometrial layer relative to control littermates
|
• both untreated and eCG+hCG-treated immature (day 25) female mutants show a significant reduction in the length and diameter of uterine horns relative to control littermates
|
• mutant uteri are hypotrophic, approximately two thirds the length of control littermates, and contain much less smooth muscle
|
• adult day-1 pregnant female mutants display reduced uterine weights relative to age-matched control littermates
|
• unlike embryos developing in wild-type females, embryos in mutant females fail to enter the uterus on day 4 of pregnancy, indicating disruption of oviductal transport; most are found in the upper one third of the oviduct instead of the uterus
• only a few embryos progress through the oviduct to the isthmus; however, these are mostly fragmented and some zonae pellucidae are lost
• in contrast, in vitro cultured pronuclear (day-1) embryos collected from mutant donors develop at a similar rate as those derived from wild-type females
|
• female mutants exhibit decreased numbers of naturally ovulated cumulus-oocyte complexes relative to control littermates
|
• immature eCG+hCG-treated female mutants display a reduced ovulation rate relative to similarly treated wild-type females
• immature mutant females given eCG alone (46 hrs) exhibit fewer large antral follicles in their ovaries than similarly treated control littermates
|
• embryos collected from mutant females on day-3 of pregnancy appear developmentally delayed relative to control embryos
• embryos collected from mutant females on day-4 of pregnancy exhibit increased fragmentation and degeneration relative to control embryos
• however, in vitro fertilized oocytes derived from mutant donor mice are able to establish a pregnancy in wild-type recipients with normal fetal development up to at least E15
|
• at day-6 and -7 of pregnancy, mutant females exhibit no evidence of implantation; in contrast, all wild-type females display 9.8 0.4 implantation sites per dam
|
• mutant females fail to produce any offspring over a 5-month breeding period with adult wild-type males of known fertility
• in contrast, male mutants are able to sire multiple litters with wild-type females
|
N |
• eCG+hCG-treated immature female mutants show no significant changes in estrogen levels relative to control littermates
|
• on day-6 of pregnancy, mutant females show a slight (24%) decrease in serum progesterone levels relative to controls
• however, no significant changes in serum progesterone concentrations are noted through day-4 of pregnancy
|
• both eCG+hCG-treated immature and adult pregnant female mutants exhibit reduced numbers of uterine glands relative to control littermates
|
• adult day-1 pregnant female mutants display reduced ovarian weights relative to age-matched control littermates
|
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• fallopian tube cancers subsequently spread to envelop the ovaries and then aggressively metastasize throughout the abdominal cavity, including the mesentery and pancreas, with prominent cancer lesions on the diaphragm and peritoneal membrane
|
• females develop early high-grade serous carcinomas in the fallopian tube
|
• tumors are characterized by complex papillae and glands forming slit-like spaces nad solid sheets of tumor cells with pleomorphic nuclei, prominent nucleoli, and high mitotic activity, resembling high-grade human serous ovarian cancer
• origin of the serous carcinomas, however is the fallopian tube
|
• after developing ascites, 100% of females die from the metastatic cancers between 6.5 and 13 months of age
|
• tumors are characterized by complex papillae and glands forming slit-like spaces nad solid sheets of tumor cells with pleomorphic nuclei, prominent nucleoli, and high mitotic activity, resembling high-grade human serous ovarian cancer
• origin of the serous carcinomas, however is the fallopian tube
|
• abnormal proliferation begins in the stromal compartment, not in the epithelial layer, of the fallopian tube; tumor cells in the stroma express epithelial markers indicating that stromal cells in the fallopian tube undergo a transition to an epithelial cell type during carcinoma formation
|
• tumors are characterized by complex papillae and glands forming slit-like spaces nad solid sheets of tumor cells with pleomorphic nuclei, prominent nucleoli, and high mitotic activity, resembling high-grade human serous ovarian cancer
• origin of the serous carcinomas, however is the fallopian tube
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
ovarian cancer | DOID:2394 |
OMIM:167000 OMIM:607893 |
J:182161 |
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• mice show widespread peritoneal metastases, including omentum and diaphragm
• the overall metastatic tumor burden in fallopian tube-removed mice is less extensive than that of intact mice
|
• mice develop massive high-grade serous carcinomas that always arise from the fallopian tube
• however when fallopian tubes are removed, mice develop high-grade serous carcinomas originating from the ovary, indicating that the ovary can be a source of carcinomas but is less dominant in tumorigenesis than the fallopian tube
|
• ovary has on overgrowth of tumors composed of cells showing nuclear pleiomprhism, irregular chromatin distribution, macronucleoli, increased mitotic activity and widespread apoptosis resembling high-grade human serous ovarian cancer
|
• premature death starting around 6 months of age with all mice dying by around 8 months of age
• fallopian tube-removed mice die at around 8-14 months of age after inducing ascites
|
• ovary has on overgrowth of tumors composed of cells showing nuclear pleiomprhism, irregular chromatin distribution, macronucleoli, increased mitotic activity and widespread apoptosis resembling high-grade human serous ovarian cancer
|
• ovary has on overgrowth of tumors composed of cells showing nuclear pleiomprhism, irregular chromatin distribution, macronucleoli, increased mitotic activity and widespread apoptosis resembling high-grade human serous ovarian cancer
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
ovarian cancer | DOID:2394 |
OMIM:167000 OMIM:607893 |
J:222579 |
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• 70% of mice develop granulosa-cell tumors in the ovary
|
• 30% of mice develop high-grade serous carcinoma originating in the ovary
• however, mice do not develop serous carcinomas originating from the fallopian tube
|
• serous carcinoma spreads throughout the peritoneal cavity, to the omentum and across the peritoneal membrane, including the mesentery and diaphragm
|
• median survival is 11.2 months of age, with mice dying between 7.6 and 15.3 months of age
|
• 70% of mice develop granulosa-cell tumors in the ovary
|
• 30% of mice develop high-grade serous carcinoma originating in the ovary
• however, mice do not develop serous carcinomas originating from the fallopian tube
|
• 70% of mice develop granulosa-cell tumors in the ovary
|
• 30% of mice develop high-grade serous carcinoma originating in the ovary
• however, mice do not develop serous carcinomas originating from the fallopian tube
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
ovarian cancer | DOID:2394 |
OMIM:167000 OMIM:607893 |
J:222579 |
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
(J:91352)
(J:145805)
|
• adult ovaries show a reduction in the total number of ovarian follicles
(J:91352)
• at P21 (just before the initiation of puberty), the number of growing follicles as well as the total number of follicles is significantly reduced
(J:145805)
|
• at P21, the number of primary follicles is significantly decreased
|
• at P21, the number of primordial follicles (the primordial follicle pool) is significantly decreased
• decreased reserve of follicles persists into adulthood
|
• at P21, the number of small pre-antral follicles is significantly decreased
|
• at P21, the number of antral follicles is significantly decreased
|
• adult ovaries exhibit the normal range of follicles up to the preovulatory stage but no corpora lutea, suggesting a defect in the final steps of folliculogenesis and/or ovulation
|
• the few remaining ovarian follicles contain hemorrhagic cysts
|
• adult ovaries weigh significantly less than those from wild-type controls (1.79 +/- 0.15 mg versus 7.39 +/- 0.52 mg)
|
• adult ovaries are normally positioned adjacent to the oviducts but appear hypoplastic
(J:91352)
• however, at E14.5 and E16.5, ovaries and internal genital structures show no differences in size or histology relative to wild-type ovaries
(J:91352)
(J:145805)
|
• in adult males, the lumens of the seminiferous tubules fail to open, suggesting impaired Sertoli cell secretion of fluid
|
• at E14.5, testes are located adjacent to the kidneys but are significantly smaller and do not contain distinct testes cords
• at E16.5, testes remain smaller than wild-type testes but have organized into testicular cords
• delayed testis development is associated with decreased Leydig cell expression of essential components of testosterone biosynthesis
|
• at E14.5, testes display delayed organization of the testes cords
|
• at E14.5 and E16.5, testes are significantly smaller than wild-type
|
• adult male mice display significantly hypoplastic testes
• at E14.5 and E16.5, decreased testis size is associated with reduced cell proliferation in somatic cells of the testes
|
• testes remain at the level of the bladder within the abdominal cavity
• however, no structures derived from the Mullerian ducts (such as oviducts or uterus) are observed
|
• adult ovaries show significantly reduced basal and eCG-stimulated expression of Amh (anti-Mullerian hormone) as well as decreased eCG-induced ovarian expression of aromatase (Cyp19a1) and cyclin D2 (Ccnd2) relative to control ovaries
• in contrast, ovaries exhibit increased basal expression of Inha (inhibin-alpha) but -- unlike control ovaries -- fail to show increased Inha expression in response to eCG stimulation
|
• the few remaining ovarian follicles contain hemorrhagic cysts
|
• granulosa cells of growing follicles show significantly reduced expression of CCND2 (cyclin D2) and MKI67 (Ki67) but increased expression of CDKN1B (p27), suggesting impaired granulosa cell proliferation
|
• at 8-10 weeks of age, uterine histology revealed a reduction in epithelial, myometrial, and stromal layers
|
• the glandular elements of the endometrial layer appear less complex
|
• endometrial glands exhibit a less differentiated glandular structure than in control uteri
|
• only a few scattered endometrial glands are detected in the stroma
|
• at 8-10 weeks of age, uterine weight is significantly lower than in control females
|
• spermatogonia fail to develop into mature sperm
|
• male mice display significantly hypoplastic internal genitalia
|
• both male and female mice display no postnatal sexual maturation
• however, both male and female mice exhibit normal external genitalia at birth
|
• absence of corpora lutea indicates impaired ovulation
|
• after gonadotropin-induced ovulation, 8- to 12-wk-old females ovulate an average of only 1.0 +/- 0.7 oocytes per female versus 35.3 +/- 2.9 oocytes per female in wild-type controls (i.e. females heterozygous for the Nr5a1tm2Klp allele but negative for the Amhr2tm3(cre)Bhr allele)
• following superovulation induction, 80% of females had no oocytes retrieved from the oviducts; 2 females released 3 and 4 oocytes each, some found in immature stages of development
|
• estrous cycles range from abnormally prolonged cycles (50%) to complete acyclicity (50%)
|
• when observed, estrous phase length is significantly shorter than in control females
|
• 50% of females are completely acyclic
|
• 50% of females show abnormally prolonged cycles
|
• female mice are sterile
(J:91352)
• when mated with young wild-type male mice, no adult females delivered any pups during a >1 yr observation period
(J:145805)
|
• male mice are sterile
|
• adrenal glands are smaller than wild-type but appear histologically intact
|
• the glandular elements of the endometrial layer appear less complex
|
• endometrial glands exhibit a less differentiated glandular structure than in control uteri
|
• only a few scattered endometrial glands are detected in the stroma
|
(J:91352)
(J:145805)
|
• adult ovaries show a reduction in the total number of ovarian follicles
(J:91352)
• at P21 (just before the initiation of puberty), the number of growing follicles as well as the total number of follicles is significantly reduced
(J:145805)
|
• at P21, the number of primary follicles is significantly decreased
|
• at P21, the number of primordial follicles (the primordial follicle pool) is significantly decreased
• decreased reserve of follicles persists into adulthood
|
• at P21, the number of small pre-antral follicles is significantly decreased
|
• at P21, the number of antral follicles is significantly decreased
|
• adult ovaries exhibit the normal range of follicles up to the preovulatory stage but no corpora lutea, suggesting a defect in the final steps of folliculogenesis and/or ovulation
|
• the few remaining ovarian follicles contain hemorrhagic cysts
|
• adult ovaries weigh significantly less than those from wild-type controls (1.79 +/- 0.15 mg versus 7.39 +/- 0.52 mg)
|
• adult ovaries are normally positioned adjacent to the oviducts but appear hypoplastic
(J:91352)
• however, at E14.5 and E16.5, ovaries and internal genital structures show no differences in size or histology relative to wild-type ovaries
(J:91352)
(J:145805)
|
• in adult males, the lumens of the seminiferous tubules fail to open, suggesting impaired Sertoli cell secretion of fluid
|
• at E14.5, testes are located adjacent to the kidneys but are significantly smaller and do not contain distinct testes cords
• at E16.5, testes remain smaller than wild-type testes but have organized into testicular cords
• delayed testis development is associated with decreased Leydig cell expression of essential components of testosterone biosynthesis
|
• at E14.5, testes display delayed organization of the testes cords
|
• at E14.5 and E16.5, testes are significantly smaller than wild-type
|
• adult male mice display significantly hypoplastic testes
• at E14.5 and E16.5, decreased testis size is associated with reduced cell proliferation in somatic cells of the testes
|
• testes remain at the level of the bladder within the abdominal cavity
• however, no structures derived from the Mullerian ducts (such as oviducts or uterus) are observed
|
• adult ovaries show significantly reduced basal and eCG-stimulated expression of Amh (anti-Mullerian hormone) as well as decreased eCG-induced ovarian expression of aromatase (Cyp19a1) and cyclin D2 (Ccnd2) relative to control ovaries
• in contrast, ovaries exhibit increased basal expression of Inha (inhibin-alpha) but -- unlike control ovaries -- fail to show increased Inha expression in response to eCG stimulation
|
• the few remaining ovarian follicles contain hemorrhagic cysts
|
• granulosa cells of growing follicles show significantly reduced expression of CCND2 (cyclin D2) and MKI67 (Ki67) but increased expression of CDKN1B (p27), suggesting impaired granulosa cell proliferation
|
• adult males exhibit plasma testosterone levels that are indistinguishable from those of prepubertal wild-type males
|
• in response to eCG stimulation, 8-12-wk-old females show a significantly blunted increase in plasma estradiol levels relative to control females
• however, basal plasma estradiol levels are normal
|
• basal plasma FSH levels are significantly higher than in wild-type females
|
• the few remaining ovarian follicles contain hemorrhagic cysts
|
• granulosa cells of growing follicles show significantly reduced expression of CCND2 (cyclin D2) and MKI67 (Ki67) but increased expression of CDKN1B (p27), suggesting impaired granulosa cell proliferation
|
• the few remaining ovarian follicles contain hemorrhagic cysts
|
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• ovarian tumors are seen in 3-12 month old mice
• tumors are bilateral and larger than those of Kit homozygous mutants and are almost entirely positive for cytokeratin 8, suggesting epithelial origin and show active proliferation
|
• about 50% of ovaries contain mixed epithelial and granulosa tumors
|
• about 50% of ovaries contain mixed epithelial and granulosa tumors
|
• ovarian tumors are seen in 3-12 month old mice
• tumors are bilateral and larger than those of Kit homozygous mutants and are almost entirely positive for cytokeratin 8, suggesting epithelial origin and show active proliferation
|
• about 50% of ovaries contain mixed epithelial and granulosa tumors
|
• about 50% of ovaries contain mixed epithelial and granulosa tumors
|
• ovarian tumors are seen in 3-12 month old mice
• tumors are bilateral and larger than those of Kit homozygous mutants and are almost entirely positive for cytokeratin 8, suggesting epithelial origin and show active proliferation
|
• about 50% of ovaries contain mixed epithelial and granulosa tumors
|
• about 50% of ovaries contain mixed epithelial and granulosa tumors
|
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• female mice become infertile after 3 to 4 months of breeding
|
• after 3 months of age, 100% of female mice have unilateral or bilateral ovarian tumors
|
• over 70% of female mice have metastic ovarian cancer by 1 year of age
|
• 100% of male mice by 7 months of age exhibit tumors in the testis
• early stage tumors appear to be sex cord stromal tumors with Sertoli and Leydig cell differentiation
|
• female mice become infertile after 3 to 4 months of breeding
|
• slight infertility, with a 16% decrease in litters per month when bred to wild-type females
|
• after 3 months of age, 100% of female mice have unilateral or bilateral ovarian tumors
|
• over 70% of female mice have metastic ovarian cancer by 1 year of age
|
• 100% of male mice by 7 months of age exhibit tumors in the testis
• early stage tumors appear to be sex cord stromal tumors with Sertoli and Leydig cell differentiation
|
• found in 50% of female mice over 9 months in age
• found in about 60% of male mice by 11 months in age
|
• after 3 months of age, 100% of female mice have unilateral or bilateral ovarian tumors
|
• over 70% of female mice have metastic ovarian cancer by 1 year of age
|
• early stage tumors appear to be sex cord stromal tumors with Sertoli and Leydig cell differentiation
• 100% of male mice by 7 months of age exhibit tumors in the testis
|
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• female mice become infertile after 3 to 4 months of breeding
|
• after 3 months of age, 100% of female mice have unilateral or bilateral ovarian tumors
|
• over 70% of female mice have metastic ovarian cancer by 1 year of age
|
• 100% of male mice by 7 months of age exhibit tumors in the testis
• early stage tumors appear to be sex cord stromal tumors with Sertoli and Leydig cell differentiation
|
• female mice become infertile after 3 to 4 months of breeding
|
• slight infertility, with a 16% decrease in litters per month when bred to wild-type females
|
• after 3 months of age, 100% of female mice have unilateral or bilateral ovarian tumors
|
• over 70% of female mice have metastic ovarian cancer by 1 year of age
|
• 100% of male mice by 7 months of age exhibit tumors in the testis
• early stage tumors appear to be sex cord stromal tumors with Sertoli and Leydig cell differentiation
|
• found in 50% of female mice over 9 months in age
• found in about 60% of male mice by 11 months in age
|
• after 3 months of age, 100% of female mice have unilateral or bilateral ovarian tumors
|
• over 70% of female mice have metastic ovarian cancer by 1 year of age
|
• 100% of male mice by 7 months of age exhibit tumors in the testis
• early stage tumors appear to be sex cord stromal tumors with Sertoli and Leydig cell differentiation
|
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• decreased number of primordial, primary, secondary and preantral follicles at 36 weeks old
|
• increased number of atretic follicles at 36 weeks of age
|
• a small reduction in fertility
|
• 50% decrease in global tri-methylated H3K4 levels in granulosa cells
|
• increased serum FSH levels at 8 weeks old
|
• decreased number of primordial, primary, secondary and preantral follicles at 36 weeks old
|
• increased number of atretic follicles at 36 weeks of age
|
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• 33% of mutant females survived to 32 weeks
• 50% survival at approximately 29 week of age
|
• develop granulosa cell tumors early during sexual maturity (at least by 8 wk of age)
• tumor characteristic: lacked nuclear grooves, infrequently contained Call-Exner bodies, high mitotic index, increased serum Inhibin A and anti-Mullerian hormone (AMH) level
• AMH expression in primary tumors and tumor cells as they metastasize outside the ovary
|
• develop granulosa cell tumors early during sexual maturity (at least by 8 wk of age)
• tumor characteristic: lacked nuclear grooves, infrequently contained Call-Exner bodies, high mitotic index, increased serum Inhibin A and anti-Mullerian hormone (AMH) level
• AMH expression in primary tumors and tumor cells as they metastasize outside the ovary
|
• develop granulosa cell tumors early during sexual maturity (at least by 8 wk of age)
• tumor characteristic: lacked nuclear grooves, infrequently contained Call-Exner bodies, high mitotic index, increased serum Inhibin A and anti-Mullerian hormone (AMH) level
• AMH expression in primary tumors and tumor cells as they metastasize outside the ovary
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
ovarian cancer | DOID:2394 |
OMIM:167000 OMIM:607893 |
J:157310 |
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• 33% of mutant females survived to 32 weeks
• 50% survival at approximately 29 week of age
|
• develop granulosa cell tumors early during sexual maturity (at least by 8 wk of age)
• tumor characteristic: lacked nuclear grooves, infrequently contained Call-Exner bodies, high mitotic index, increased serum Inhibin A and anti-Mullerian hormone (AMH) level
• AMH expression in primary tumors and tumor cells as they metastasize outside the ovary
|
• develop granulosa cell tumors early during sexual maturity (at least by 8 wk of age)
• tumor characteristic: lacked nuclear grooves, infrequently contained Call-Exner bodies, high mitotic index, increased serum Inhibin A and anti-Mullerian hormone (AMH) level
• AMH expression in primary tumors and tumor cells as they metastasize outside the ovary
|
• develop granulosa cell tumors early during sexual maturity (at least by 8 wk of age)
• tumor characteristic: lacked nuclear grooves, infrequently contained Call-Exner bodies, high mitotic index, increased serum Inhibin A and anti-Mullerian hormone (AMH) level
• AMH expression in primary tumors and tumor cells as they metastasize outside the ovary
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
ovarian cancer | DOID:2394 |
OMIM:167000 OMIM:607893 |
J:157310 |
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• 33% of mutant females survived to 32 weeks
• 50% survival at approximately 29 week of age
|
• develop granulosa cell tumors early during sexual maturity (at least by 8 wk of age)
• tumor characteristic: lacked nuclear grooves, infrequently contained Call-Exner bodies, high mitotic index, increased serum Inhibin A and anti-Mullerian hormone (AMH) level
• AMH expression in primary tumors and tumor cells as they metastasize outside the ovary
|
• develop granulosa cell tumors early during sexual maturity (at least by 8 wk of age)
• tumor characteristic: lacked nuclear grooves, infrequently contained Call-Exner bodies, high mitotic index, increased serum Inhibin A and anti-Mullerian hormone (AMH) level
• AMH expression in primary tumors and tumor cells as they metastasize outside the ovary
|
• develop granulosa cell tumors early during sexual maturity (at least by 8 wk of age)
• tumor characteristic: lacked nuclear grooves, infrequently contained Call-Exner bodies, high mitotic index, increased serum Inhibin A and anti-Mullerian hormone (AMH) level
• AMH expression in primary tumors and tumor cells as they metastasize outside the ovary
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
ovarian cancer | DOID:2394 |
OMIM:167000 OMIM:607893 |
J:157310 |
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• severe ovarian phenotypes were always accompanied by variable degrees of growth retardation, poor body condition, a disheveled appearance, and frequently premature death
|
• ovaries developed far fewer preovulatory and ovulatory follicles in response to gonadotropin treatment than control ovaries and often appeared to have fewer large secondary follicles as well
|
• ovaries developed far fewer preovulatory and ovulatory follicles in response to gonadotropin treatment than control ovaries and often appeared to have fewer large secondary follicles as well
• fewer healthy antral follicles in 42-d-old mutant female
• small subset of mutant female had very small ovaries that were devoid of antral follicles and corpora lutea at 8?12 wk of age
|
• only 49% the size of those of littermate controls
• all stages of follicular development and corpora lutea could be identified in most adult
|
• ovaries developed far fewer preovulatory and ovulatory follicles in response to gonadotropin treatment than control ovaries and often appeared to have fewer large secondary follicles as well
|
• ovaries developed far fewer preovulatory and ovulatory follicles in response to gonadotropin treatment than control ovaries and often appeared to have fewer large secondary follicles as well
• fewer healthy antral follicles in 42-d-old mutant female
• small subset of mutant female had very small ovaries that were devoid of antral follicles and corpora lutea at 8?12 wk of age
|
• only 49% the size of those of littermate controls
• all stages of follicular development and corpora lutea could be identified in most adult
|
• average litter size was only 54% that of the control group
|
• severe ovarian phenotypes were always accompanied by variable degrees of growth retardation
|
• severe developmental anomalies of the kidneys having few glomeruli
|
• severe ovarian phenotypes were always accompanied by a disheveled appearance
|
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• newborn males have both male and female reproductive tracts
|
• mesenchyme is less condensed
|
• decrease in apoptosis in the epithelium
|
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• mutants show complete or partial loss of germ cells
|
• adult Sertoli cells show disruption of cell cycle quiescence and thus increased proliferation in mice older than 4 months of age
|
• mutants show complete or partial loss of germ cells
|
• testicular junction integrity is compromised
|
• adult Sertoli cells show disruption of cell cycle quiescence and thus increased proliferation in mice older than 4 months of age
|
• mutants show complete or partial loss of germ cells and tubules with only Sertoli cells
|
• testes show vacuolization of seminiferous epithelium
|
• Sertoli cells show disruption of the spoke-like pattern of microtubules and loss of apical extensions, and disruption of actin filament arrangement, indicating disruption of polarity
|
• in adults
|
• in adults
|
• immature round germ cells are seen in the epididymides whereas only mature elongated germ cells are seen in controls
|
• testicular junction integrity is compromised
|
• adult Sertoli cells show disruption of cell cycle quiescence and thus increased proliferation in mice older than 4 months of age
|
• mutants show complete or partial loss of germ cells and tubules with only Sertoli cells
|
• testes show vacuolization of seminiferous epithelium
|
• Sertoli cells show disruption of the spoke-like pattern of microtubules and loss of apical extensions, and disruption of actin filament arrangement, indicating disruption of polarity
|
• in adults
|
• in adults
|
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
N |
• young adult females show no significant differences in the onset of puberty, length of the estrous cycle, or ovarian follicular development relative to controls
(J:173711)
|
N |
• at 2.5 and 6 months of age, males show normal seminal vesicle weights relative to controls
(J:169018)
|
• by 6 months of age, males show marked depletion of germ cells in the later stages of development
|
• by 6 months of age, multinucleated giant cells, syncytia of degenerating spermatids, are found in the seminiferous tubules
|
• caspase-3 immunostaining revealed increased germ cell apoptosis at 6 months of age
|
• males show an age-dependent decline in the % of progressively motile sperm
|
• males show an age-dependent decline in the % of total motile sperm
|
• ovaries of eCG plus hCG-treated immature females are significantly smaller than those in similarly treated control ovaries
• however, unstimulated ovaries exhibit normal weight and gross morphology
|
• by 6 months of age, 6 of 7 (86%) ovaries exhibit very large, non-hemorrhagic cysts versus 0 of 10 (0%) ovaries from control females
• ovarian cysts are lined by a flattened epithelium containing scattered ciliated cells
|
• ovaries of eCG plus hCG-treated immature females show hemorrhagic follicular cysts on their surface, not observed in similarly treated control ovaries
|
• at 2.5 and 4 months of age, the seminiferous tubule epithelium shows signs of vacuolar degeneration
• at 4 months, spermatocytes and spermatids are prematurely released from the seminiferous epithelium and sloughed into the epididymis
• by 6 months, tubules show progressive atrophy suggesting marked depletion of germ cells; any remaining germ cells are abnormally positioned within the seminiferous epithelium
|
• at 2.5 months of age, Sertoli cells exhibit vacuolation and accumulation of large lipid droplets
• Sertoli cell vacuoles are surrounded by membrane and occasionally contain multivesicular body-like structures
• vacuolar membranes are often lined by actin filament bundles with endoplasmic reticulum cisternae located beneath them, suggesting germ cell loss
• number of GATA4-immunoreactive Sertoli cells declines dramatically between 4 and 6 months of age, whereas the number of GATA1-and AR-immunoreactive Sertoli cells remains constant
|
• at 2.5 and 4 months of age, the seminiferous tubule epithelium shows signs of vacuolar degeneration
• by 6 months, tubules show progressive atrophy at all stages of the seminiferous epithelial cycle as well as dystrophic calcification in severely degenerated tubules
|
• testes are overtly smaller at 6 months of age
• however, male external genitalia and testicular descent appear normal
|
• average testis weight is 59% and 41% of control weight at 6 and 8 months of age, respectively
• however, body weight is not significantly altered
|
• males develop age-dependent testicular atrophy
|
• ovaries of gonadotropin-stimulated immature females are significantly smaller, release fewer or no oocytes, and exhibit cystic changes and significantly lower mRNA levels of the steroidogenic gene Cyp19a1 than gonadotropin-stimulated control ovaries, with a trend towards reduced Star and Cyp11a1 expression
• however, basal ovarian mRNA levels of Star, Cyp11a1 and Cyp19a1 are normal
|
• permeability of the blood-testis barrier is significantly increased by 6 months of age
|
• spermatogenesis is impaired with sloughing of spermatocytes and spermatids into the seminiferous tubule lumen, formation of multinucleated giant cells, and dystrophic calcification
|
• at 6 months of age, caudal epididymal sperm concentrations are significantly lower than those in control males
|
• by 6 months of age, the number of elongated spermatids is decreased
|
• in response to exogenous gonadotropins, immature females show a significant decline in oocyte yield relative to superovulated controls
• however, serum E2 levels of eCG-treated juvenile females are not altered
|
• one-third of superovulated females tested release no oocytes
|
• 6 of 18 (33%) 2-mo-old females failed to produce offspring versus only 1 of 20 (5%) of control females
|
• when housed with males of proven fertility, most 2-mo-old females are sub-fertile
|
• average litter size produced by females is about half that of control females
|
• males show an abrupt decline in fertility after the first 5 months of life
• however, males copulate with females at a normal rate
|
• by 6 months of age, the number of elongated spermatids is decreased
|
• by 6 months of age, males show marked depletion of germ cells in the later stages of development
|
• at 6 months of age, caudal epididymal sperm concentrations are significantly lower than those in control males
|
• by 6 months of age, multinucleated giant cells, syncytia of degenerating spermatids, are found in the seminiferous tubules
|
• caspase-3 immunostaining revealed increased germ cell apoptosis at 6 months of age
|
• males show an age-dependent decline in the % of progressively motile sperm
|
• males show an age-dependent decline in the % of total motile sperm
|
• ovaries of eCG plus hCG-treated immature females are significantly smaller than those in similarly treated control ovaries
• however, unstimulated ovaries exhibit normal weight and gross morphology
|
• by 6 months of age, 6 of 7 (86%) ovaries exhibit very large, non-hemorrhagic cysts versus 0 of 10 (0%) ovaries from control females
• ovarian cysts are lined by a flattened epithelium containing scattered ciliated cells
|
• ovaries of eCG plus hCG-treated immature females show hemorrhagic follicular cysts on their surface, not observed in similarly treated control ovaries
|
• at 2.5 and 4 months of age, the seminiferous tubule epithelium shows signs of vacuolar degeneration
• at 4 months, spermatocytes and spermatids are prematurely released from the seminiferous epithelium and sloughed into the epididymis
• by 6 months, tubules show progressive atrophy suggesting marked depletion of germ cells; any remaining germ cells are abnormally positioned within the seminiferous epithelium
|
• at 2.5 months of age, Sertoli cells exhibit vacuolation and accumulation of large lipid droplets
• Sertoli cell vacuoles are surrounded by membrane and occasionally contain multivesicular body-like structures
• vacuolar membranes are often lined by actin filament bundles with endoplasmic reticulum cisternae located beneath them, suggesting germ cell loss
• number of GATA4-immunoreactive Sertoli cells declines dramatically between 4 and 6 months of age, whereas the number of GATA1-and AR-immunoreactive Sertoli cells remains constant
|
• at 2.5 and 4 months of age, the seminiferous tubule epithelium shows signs of vacuolar degeneration
• by 6 months, tubules show progressive atrophy at all stages of the seminiferous epithelial cycle as well as dystrophic calcification in severely degenerated tubules
|
• testes are overtly smaller at 6 months of age
• however, male external genitalia and testicular descent appear normal
|
• average testis weight is 59% and 41% of control weight at 6 and 8 months of age, respectively
• however, body weight is not significantly altered
|
• males develop age-dependent testicular atrophy
|
• ovaries of gonadotropin-stimulated immature females are significantly smaller, release fewer or no oocytes, and exhibit cystic changes and significantly lower mRNA levels of the steroidogenic gene Cyp19a1 than gonadotropin-stimulated control ovaries, with a trend towards reduced Star and Cyp11a1 expression
• however, basal ovarian mRNA levels of Star, Cyp11a1 and Cyp19a1 are normal
|
• permeability of the blood-testis barrier is significantly increased by 6 months of age
|
N |
• at 5-8 months of age, males show normal circulating levels of FSH and inhibin B relative to controls
|
• serum anti-Mullerian hormone (AMH) levels are normal in 2.5-mo-old females but significantly lower than in female controls at 6 months of age, indicating impaired granulosa cell function
|
• by 6 months of age, 6 of 7 (86%) ovaries exhibit very large, non-hemorrhagic cysts versus 0 of 10 (0%) ovaries from control females
• ovarian cysts are lined by a flattened epithelium containing scattered ciliated cells
|
• ovaries of eCG plus hCG-treated immature females show hemorrhagic follicular cysts on their surface, not observed in similarly treated control ovaries
|
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
N |
• females exhibit normal fertility and ovarian follicle development relative to wild-type controls
|
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
N |
• Mullerian duct regression is normal
|
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
N |
• most females lack ovarian abnormalities
|
• 5 of 70 females developed ovarian tumors
(J:142150)
• ovarian tumors are granulosa cell tumors
(J:142150)
• 65% of mice develop granulosa-cell type tumors in the ovary
(J:222579)
• however, mice do not develop ovarian or fallopian tube high grade serous carcinoma
(J:222579)
|
• many females fail to carry pregnancies to term
|
• many females have small litters due to fetal death after E9.5
|
• 5 of 70 females developed ovarian tumors
(J:142150)
• ovarian tumors are granulosa cell tumors
(J:142150)
• 65% of mice develop granulosa-cell type tumors in the ovary
(J:222579)
• however, mice do not develop ovarian or fallopian tube high grade serous carcinoma
(J:222579)
|
• ganulosa cell tumors are aggressive and metastasize to the lungs
|
• 5 of 70 females developed ovarian tumors
(J:142150)
• ovarian tumors are granulosa cell tumors
(J:142150)
• 65% of mice develop granulosa-cell type tumors in the ovary
(J:222579)
• however, mice do not develop ovarian or fallopian tube high grade serous carcinoma
(J:222579)
|
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• presence of nests of dysplastic cells are seen in the ovaries of newborn mice and E20.5, but not E18.5, indicating that tumor growth begins perinatally
|
• females develop ovarian granulosa cell bilateral tumors with 100% penetrance from an early age
|
• 100% penetrance of aggressive testicular cancer
• tumors are first observable at 5 weeks of age, and by 3 months of age, about 70% of mice have unilateral testicular tumors and 30% have bilateral tumors
• tumors exhibit characteristics of granulosa cell tumors of the testis and not Sertoli cell tumors
|
• metastasis is not observed, but this might be that mice do not have sufficient time to develop metastasis due to early lethality, however, when granulosa cell tumors are removed at 6 weeks of age, mice show development of large lung metastases 6-16 weeks later, indicating that tumors indeed are metastatic
(J:142150)
• 44% of mice develop pulmonary metastases by 4 months
(J:149060)
|
• presence of nests of dysplastic cells are seen in the ovaries of newborn mice and E20.5, but not E18.5, indicating that tumor growth begins perinatally
|
• females develop ovarian granulosa cell bilateral tumors with 100% penetrance from an early age
|
• seminiferous tubule degeneration is seen by 3 weeks of age
|
• 100% penetrance of aggressive testicular cancer
• tumors are first observable at 5 weeks of age, and by 3 months of age, about 70% of mice have unilateral testicular tumors and 30% have bilateral tumors
• tumors exhibit characteristics of granulosa cell tumors of the testis and not Sertoli cell tumors
|
• presence of nests of dysplastic cells are seen in the ovaries of newborn mice and E20.5, but not E18.5, indicating that tumor growth begins perinatally
|
• females develop ovarian granulosa cell bilateral tumors with 100% penetrance from an early age
|
• seminiferous tubule degeneration is seen by 3 weeks of age
|
• 100% penetrance of aggressive testicular cancer
• tumors are first observable at 5 weeks of age, and by 3 months of age, about 70% of mice have unilateral testicular tumors and 30% have bilateral tumors
• tumors exhibit characteristics of granulosa cell tumors of the testis and not Sertoli cell tumors
|
• pulmonary tumor cell embolisms
|
• extrensive extramedullary hematopoiesis
|
• female mice die before 9 weeks of age
|
• pulmonary tumor cell embolisms
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
granulosa cell tumor | DOID:2999 | J:142150 | ||
testicular granulosa cell tumor | DOID:5331 | J:149060 |
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• female mutants develop granulosa cell tumors by 3 weeks of age
|
• male mutants develop testicular granulosa cell tumors by 5 weeks of age
|
• female mutants develop granulosa cell tumors by 3 weeks of age
|
• male mutants develop testicular granulosa cell tumors by 5 weeks of age
|
• female mutants develop granulosa cell tumors by 3 weeks of age
|
• male mutants develop testicular granulosa cell tumors by 5 weeks of age
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
granulosa cell tumor | DOID:2999 | J:186144 | ||
juvenile type testicular granulosa cell tumor | DOID:6032 | J:186144 | ||
ovarian cancer | DOID:2394 |
OMIM:167000 OMIM:607893 |
J:186144 |
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• female mutants develop granulosa cell tumors by 12-14 weeks of age
|
• male mutants develop granulosa cell tumors of the testis by 4-5 months of age; tumors do not spread or metastasize
|
• female mutants develop granulosa cell tumors by 12-14 weeks of age
|
• seminiferous tubule degeneration is seen by 4 weeks of age
|
• male mutants develop granulosa cell tumors of the testis by 4-5 months of age; tumors do not spread or metastasize
|
• female mutants develop granulosa cell tumors by 12-14 weeks of age
|
• seminiferous tubule degeneration is seen by 4 weeks of age
|
• male mutants develop granulosa cell tumors of the testis by 4-5 months of age; tumors do not spread or metastasize
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
granulosa cell tumor | DOID:2999 | J:186144 | ||
juvenile type testicular granulosa cell tumor | DOID:6032 | J:186144 | ||
ovarian cancer | DOID:2394 |
OMIM:167000 OMIM:607893 |
J:186144 |
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
N |
• no abnormalities in testis
|
• mean mutant mesometrial maternal decidua surface area is 2.81-fold greater than in controls
• decidua are abnormal in appearance, featuring many mitotic figures in females 11.5 days pregnant, with little evidence of apoptosis, and many cells with unusually abundant cytoplasm, particularly near the trophoblast invasion front
• 9-fold decrease in apoptotic decidaul cells in mutants relative to controls
• about 2-3 days after expected parturition in the second gestation, females show necrotic decidua with transmural pyometritis and edema in the endometrial stroma
• these results indicate failure of decidual regression
|
• mutant decidua shows 2.63-fold fewer uterine natural killer cells than control females that are 11.5 dpc
|
• endometrium epithelial cells appear hypertrophic, hyperplastic, and disorganized
• about 2-3 days after expected parturition of the second gestation, females show necrotic decidua with transmural pyometritis and edema in the endometrial stroma
|
• endometrial fibrosis is seen in females beyond the first gestation at day 112.5 and day 119.45 pc
|
• thickening of the myometrium and disorganization of the muscle fibers before and throughout gestation
|
• uteri of pregnant females beyond the first gestation, show varying degrees of hyperplasia of both the uterine and glandular epithelia
|
• primiparous females exhibit reduced fertility due to increased fetal loss at E11.5
• almost all mutant females fail to carry a second litter to term; females pregnant for the second time show signs of implantation but no viable fetuses at 9.5 dpc
|
• females produce about 44% fewer pups per mating than controls
• implanted fetuses fail to develop to term due to epithelial hyperplasia and other uterine anomalies
|
• females at 11.5 days of pregnancy exhibit poorly transformed maternal vasculature in the decidua, showing persistence of the muscular layer of maternal vessels, even deep within the decidual tissue, however maternal vascular transformation appears complete by 14.5 dpc, indicating a transient delay in vasculature transformation
|
• mean mutant mesometrial maternal decidua surface area is 2.81-fold greater than in controls
• decidua are abnormal in appearance, featuring many mitotic figures in females 11.5 days pregnant, with little evidence of apoptosis, and many cells with unusually abundant cytoplasm, particularly near the trophoblast invasion front
• 9-fold decrease in apoptotic decidaul cells in mutants relative to controls
• about 2-3 days after expected parturition in the second gestation, females show necrotic decidua with transmural pyometritis and edema in the endometrial stroma
• these results indicate failure of decidual regression
|
• mutant decidua shows 2.63-fold fewer uterine natural killer cells than control females that are 11.5 dpc
|
• abnormal development of the placental labyrinth, and frequent apparent intrauterine fetal growth restriction
• by 11.5 dpc, the placental labyrinth is thin and underdeveloped in most concepti of mutant females
|
• by 11.5 dpc, trophoblast migration appears restricted by an abnormally thick maternal decidua
• fetal trophoblast glycogen cells do not migrate beyond the parietal trophoblast giant cell border by 14.5 dpc as in controls and are halted at the maternal-fetal interface
• trophoblast migration is impeded by inhibition of decidual regression and is attributable to inhibition of decidual cell apoptosis
|
• mutant decidua shows 2.63-fold fewer uterine natural killer cells than control females that are 11.5 dpc
|
• mutant decidua shows 2.63-fold fewer uterine natural killer cells than control females that are 11.5 dpc
|
• females at 11.5 days of pregnancy exhibit poorly transformed maternal vasculature in the decidua, showing persistence of the muscular layer of maternal vessels, even deep within the decidual tissue, however maternal vascular transformation appears complete by 14.5 dpc, indicating a transient delay in vasculature transformation
|
• mutant decidua shows 2.63-fold fewer uterine natural killer cells than control females that are 11.5 dpc
|
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
N |
• males are fertile and able to sire multiple litters at a normal frequency through 12 weeks of age
|
• many ovulated oocytes are not competent, suggesting that oocyte maturation is disrupted
|
• after normal ovulation, 83% of oocytes collected from the oviducts during estrus are atretic (degenerated) relative to only 4% in control females
• after superovulation, the number of atretic oocytes is 7-fold higher than that in control females
• however, the number of healthy oocytes is not significantly altered
|
• by 5 months of age, 100% of males show complete or partial loss of germ cells and tubules with only Sertoli cells
|
• Dietrick's staining showed significantly fewer primordial follicles at 12 weeks of age; immunofluorescence staining with oocyte-specific marker MVH confirmed that fewer primordial follicles are present in the cortex
• decrease in primordial follicles is more severe at 24 weeks of age
• however, number of total follicles and primordial follicles is normal at 6 weeks of age
|
• number of atretic follicles is normal at 6 weeks but significantly increased at 12 weeks of age
• a non-significant trend towards a higher atretic follicle number is noted at 24 weeks
|
• ovarian folliculogenesis is disrupted
|
• testicular junction integrity is compromised
|
• adult Sertoli cells show disruption of cell cycle quiescence and thus increased proliferation in mice older than 4 months of age
|
• by 5 months of age, 100% of males show complete or partial loss of germ cells and tubules with only Sertoli cells
|
• 12 week old, but not 4 week old, testes show vacuolization of seminiferous epithelium
|
• Sertoli cells show disruption of the spoke-like pattern of microtubules and loss of apical extensions, and disruption of actin filament arrangement, indicating disruption of polarity
|
• small testis in adult males
|
• decreased testis weight in adult males
|
• at estrus, ovarian mRNA levels of Muc1 (mucin 1, transmembrane) are reduced by 50% whereas mRNA levels of Hif1a (hypoxia inducible factor 1, alpha subunit) are increased by 50% relative to control ovaries
|
• females show premature ovarian insufficiency, possibly related to increased time spent in estrus
|
• secretory epithelial cell disorganization and dysplasia is observed in the proximal portion of the oviduct, occluding the lumen
• occlusion of the proximal oviduct is likely to inhibit proper transit of embryos through the oviduct, contributing to female infertility
• however, ciliated and secretory epithelial cells of the distal oviduct appear intact
|
• at E3.5 after natural mating, bilateral swelling of the ampullas resembling hydrosalpinges is observed in all females due to occlusion of the proximal oviduct, whereas no swelling is seen in controls females
• upon puncture, blastocysts and many degenerated bodies (~75%) are released from the swollen ampulla
|
• endometrial epithelial cells continue to proliferate in E4.5 uteri, unlike in control uteri
• however, no evidence of endometrial cancer is observed
|
• females exhibit significant myometrial hyperplasia mice as they age
|
• immature round germ cells are seen in the epididymides whereas only mature elongated germ cells are seen in controls
|
• duration of diestrus is shortened
• however, serum 17beta-estradiol (E2) progesterone (P4) levels at diestrus are normal
|
• duration of the estrous stage is prolonged
• however, serum 17beta-estradiol (E2) progesterone (P4) levels at estrus are normal
|
• at E4.5 after natural mating, no implantation sites are detected, unlike in controls females
• endometrial epithelial cells continue to proliferate and Muc1 mRNA expression remains elevated in E4.5 uteri (with no changes in progesterone receptor mRNA levels), suggesting that Muc1 continued expression may contribute to failure of implantation
• transfer of E3.5 wild-type embryos into uteri of pseudopregnant mutant female mice fails, with no evidence of embryo implantation sites 4-6 days after transfer
|
• females mated with control males of known fertility fail to produce any offspring over a 5-month breeding period
• however, seminal plugs are observed suggesting normal female mating behavior
|
• many ovulated oocytes are not competent, suggesting that oocyte maturation is disrupted
|
• after normal ovulation, 83% of oocytes collected from the oviducts during estrus are atretic (degenerated) relative to only 4% in control females
• after superovulation, the number of atretic oocytes is 7-fold higher than that in control females
• however, the number of healthy oocytes is not significantly altered
|
• by 5 months of age, 100% of males show complete or partial loss of germ cells and tubules with only Sertoli cells
|
• adult Sertoli cells show disruption of cell cycle quiescence and thus increased proliferation in mice older than 4 months of age
|
• females show premature ovarian insufficiency, possibly related to increased time spent in estrus
|
• after natural mating, more E2.5 embryos are detected in the oviducts but 75% of them are degenerated embryos
• at E3.5 after natural mating, no blastocysts are detected in the uteri after flushing, unlike in control females
• however, the absolute number of good-quality embryos found in the ampullas is normal at both E2.5 and E3.5, suggesting that good-quality oocytes can develop into blastocysts
|
• Dietrick's staining showed significantly fewer primordial follicles at 12 weeks of age; immunofluorescence staining with oocyte-specific marker MVH confirmed that fewer primordial follicles are present in the cortex
• decrease in primordial follicles is more severe at 24 weeks of age
• however, number of total follicles and primordial follicles is normal at 6 weeks of age
|
• number of atretic follicles is normal at 6 weeks but significantly increased at 12 weeks of age
• a non-significant trend towards a higher atretic follicle number is noted at 24 weeks
|
• ovarian folliculogenesis is disrupted
|
• testicular junction integrity is compromised
|
• adult Sertoli cells show disruption of cell cycle quiescence and thus increased proliferation in mice older than 4 months of age
|
• by 5 months of age, 100% of males show complete or partial loss of germ cells and tubules with only Sertoli cells
|
• 12 week old, but not 4 week old, testes show vacuolization of seminiferous epithelium
|
• Sertoli cells show disruption of the spoke-like pattern of microtubules and loss of apical extensions, and disruption of actin filament arrangement, indicating disruption of polarity
|
• small testis in adult males
|
• decreased testis weight in adult males
|
• at estrus, ovarian mRNA levels of Muc1 (mucin 1, transmembrane) are reduced by 50% whereas mRNA levels of Hif1a (hypoxia inducible factor 1, alpha subunit) are increased by 50% relative to control ovaries
|
• females show premature ovarian insufficiency, possibly related to increased time spent in estrus
|
N |
• no evidence of endometrial or ovarian cancer is observed
(J:181774)
|
N |
• testicular tumors are not observed up to 10 months of age
(J:187754)
|
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• 2 of 4 females produce no oocytes upon superovulation
• however, there is no difference in the number of oocytes superovulated in the remaining 2 mice
|
• 2 of 4 females produce no oocytes upon superovulation
• however, there is no difference in the number of oocytes superovulated in the remaining 2 mice
|
• at 6 weeks, 8 to 11 weeks, and 3 months of age, the number of corpus luteums is increased compared to Inhbatm1Zuk/Inhbatm3Zuk mice
• the expression of a marker (Lhcgr) for healthy corpus luteums is increased relative to Inhbatm1Zuk/Inhbatm3Zuk mice
|
• between 8 and 11 weeks, the number of antral follicles is decreased compared to Inhbatm1Zuk/Inhbatm3Zuk mice
• at 8 months, follicles with lutenizing granulosa cells and multiple fluid-filled or hemorrhagic cysts are present
|
• between 8 and 11 weeks, the number of antral follicles is decreased compared to Inhbatm1Zuk/Inhbatm3Zuk mice
|
• at 8 months, multiple fluid-filled or hemorrhagic cysts are present that are positive for a granulose cell marker but not an epithelial marker
|
• by 8 months, the mass of the ovaries has increased 6-fold (31.5+/-2.9 mg compared to 5.2+/-2.9 mg in Inhbatm1Zuk/Inhbatm3Zuk mice)
|
• females are infertile
|
• at 8 months, multiple fluid-filled or hemorrhagic cysts are present that are positive for a granulose cell marker but not an epithelial marker
|
• by 8 months, the mass of the ovaries has increased 6-fold (31.5+/-2.9 mg compared to 5.2+/-2.9 mg in Inhbatm1Zuk/Inhbatm3Zuk mice)
|
• at 6 weeks, 8 to 11 weeks, and 3 months of age, the number of corpus luteums is increased compared to Inhbatm1Zuk/Inhbatm3Zuk mice
• the expression of a marker (Lhcgr) for healthy corpus luteums is increased relative to Inhbatm1Zuk/Inhbatm3Zuk mice
|
• between 8 and 11 weeks, the number of antral follicles is decreased compared to Inhbatm1Zuk/Inhbatm3Zuk mice
• at 8 months, follicles with lutenizing granulosa cells and multiple fluid-filled or hemorrhagic cysts are present
|
• between 8 and 11 weeks, the number of antral follicles is decreased compared to Inhbatm1Zuk/Inhbatm3Zuk mice
|
• at 8 months, multiple fluid-filled or hemorrhagic cysts are present that are positive for a granulose cell marker but not an epithelial marker
|
• by 8 months, the mass of the ovaries has increased 6-fold (31.5+/-2.9 mg compared to 5.2+/-2.9 mg in Inhbatm1Zuk/Inhbatm3Zuk mice)
|
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
N |
• mice exhibit normal testicular development and reproduction with normal testosterone production
|
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• ovaries of 3-4 month old mice contain many small abnormal follicles in which fragmented oocytes or only remnants of the zona pellucida are evident
• some follicles in 3-4 month old mice assume the appearance of testicular-like structures
|
• about 20% of mice develop granulosa cell tumors by 6-8 months of age
• most tumors from 6-11 months of age are unilateral and solid with regions of trabecular- and gyriform-like structures
• some tumors contain cystic or hemorrhagic follicle-like structures devoid of oocytes and/or regions of necrosis
|
• ovaries of 3-4 month old mice typically contain large cyst-like structures, some of which are hemorrhagic
|
• tumor bearing mice exhibit increased levels of serum inhibin A and inhibin B
|
• serum levels of estradiol are elevated in tumor bearing mice
|
• serum follicle stimulating hormone levels are below the level of detection in tumor bearing mice
|
• serum luteinizing hormone levels are below the level of detection in tumor bearing mice
|
• about 20% of mice develop granulosa cell tumors by 6-8 months of age
• most tumors from 6-11 months of age are unilateral and solid with regions of trabecular- and gyriform-like structures
• some tumors contain cystic or hemorrhagic follicle-like structures devoid of oocytes and/or regions of necrosis
|
• ovaries of 3-4 month old mice contain many small abnormal follicles in which fragmented oocytes or only remnants of the zona pellucida are evident
• some follicles in 3-4 month old mice assume the appearance of testicular-like structures
|
• about 20% of mice develop granulosa cell tumors by 6-8 months of age
• most tumors from 6-11 months of age are unilateral and solid with regions of trabecular- and gyriform-like structures
• some tumors contain cystic or hemorrhagic follicle-like structures devoid of oocytes and/or regions of necrosis
|
• ovaries of 3-4 month old mice typically contain large cyst-like structures, some of which are hemorrhagic
|
• ovaries of 3-4 month old mice typically contain large cyst-like structures, some of which are hemorrhagic
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
ovarian cancer | DOID:2394 |
OMIM:167000 OMIM:607893 |
J:232961 |
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
N |
• mice exhibit normal reproductive morphology and physiology
|
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• progressive premature germ cell loss
|
• adult Sertoli cells show disruption of cell cycle quiescence and thus increased proliferation in mice older than 4 months of age
|
• progressive premature germ cell loss
|
• testicular junction integrity is compromised
|
• adult Sertoli cells show disruption of cell cycle quiescence and thus increased proliferation in mice older than 4 months of age
|
• by 5 months of age, mutants exhibit decreased tubular width accompanied by progressive germ cell loss and tubules with only Sertoli cells, indicating a Sertoli cell only phenotype
|
• at 4 weeks, vacuolization of seminiferous epithelium is seen in a few seminiferous tubules
• by 10 weeks of age, normal germ cell arrangement in the seminiferous tubules is disrupted and prominent vacuolization of the seminiferous epithelium is seen in most of the tubules
|
• Sertoli cells show disruption of the spoke-like pattern of microtubules and loss of apical extensions, and disruption of actin filament arrangement, indicating disruption of polarity
|
|
• in adults
|
• immature round germ cells are seen in the epididymides whereas only mature elongated germ cells are seen in controls indicating defective germ cell differentiation
|
• testicular junction integrity is compromised
|
• adult Sertoli cells show disruption of cell cycle quiescence and thus increased proliferation in mice older than 4 months of age
|
• by 5 months of age, mutants exhibit decreased tubular width accompanied by progressive germ cell loss and tubules with only Sertoli cells, indicating a Sertoli cell only phenotype
|
• at 4 weeks, vacuolization of seminiferous epithelium is seen in a few seminiferous tubules
• by 10 weeks of age, normal germ cell arrangement in the seminiferous tubules is disrupted and prominent vacuolization of the seminiferous epithelium is seen in most of the tubules
|
• Sertoli cells show disruption of the spoke-like pattern of microtubules and loss of apical extensions, and disruption of actin filament arrangement, indicating disruption of polarity
|
|
• in adults
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
Peutz-Jeghers syndrome | DOID:3852 |
OMIM:175200 |
J:187754 |
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• only ~7% of mutant mice are born, indicating embryonic lethality probably due to vascular and heart anomalies resulting from ectopic cre expression
|
• by day 10 of pregnancy, formation of fetal blood vessels from the allantois is clearly absent
|
• at day 9 of pregnancy, but nor earlier, secondary TGC differentiation appears to increase because more cells are present
• by day 10 of pregnancy, many layers of secondary TGC are noted in mutant females relative to control animals
|
• at day 9 of pregnancy, the mutant uterus displays a reduced number of decidual sites with the absence of embryo or the presence of growth-retarded embryos
|
• by day 10 of pregnancy, mutant placentas show a reduction in spongiotrophoblast cell number relative to wild-type placentas
|
• by day 10 of pregnancy, the mutant labyrinth fails to develop
|
• at day 9 of pregnancy, but nor earlier, abnormal placenta development and frequent hemorrhages are observed
• by day 10 of pregnancy, the mutant labyrinth fails to develop
|
• mutant females display vaginal bleeding 10-12 days after the presence of a copulatory plug
|
• at day 9 of pregnancy, the mutant uterus displays a reduced number of decidual sites with the absence of embryo or the presence of growth-retarded embryos
|
• the circular smooth muscle layer of mutant uteri appears disorganized relative to that of wild-type uteri, as shown by anti-smooth muscle actin immunostaining
• in contrast, the mutant endometrium appears relatively normal
|
• mutant uterine horns appear shorter than those of control mice
|
• upon mating with wild-type males, mutant females exhibit a significant lower number of implantation sites per pregnant female than control females (5.3 2.4 vs 8.8 2.2, respectively)
|
• upon mating with wild-type males, mutant females display vaginal bleeding 10-12 days after the presence of a copulatory plug, indicating failure to maintain pregnancy
• at day 9 of pregnancy, most embryos are reabsorbed and a few are growth-retarded
• however, production of endogenous estradiol and progesterone remains unaffected in mutant females
|
• despite normal ovarian histology and function, mutant female mice receiving a wild-type ovary are unable to produce pups as observed before ovary transfer
• only 1 of 6 mutant females with wild-type ovaries gave birth to one pup in a 6-month period whereas wild-type females carrying mutant ovaries exhibited normal litter sizes with pups derived from the donor ovary
|
• by day 10 of pregnancy, formation of fetal blood vessels from the allantois is clearly absent
|
• mutant embryos with hemorrhage are observed
|
• mutant females display vaginal bleeding 10-12 days after the presence of a copulatory plug
|
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• female mutants develop granulosa cell tumors by 6 months of age
|
• seminiferous tubule degeneration is seen by 5 weeks of age
|
• progressive loss of spermatogenesis and testicular atrophy with reduced testis size
|
• male mutants develop granulosa cell tumors of the testis by 9-13 weeks of age
|
• female mutants develop granulosa cell tumors by 6 months of age
|
• seminiferous tubule degeneration is seen by 5 weeks of age
|
• progressive loss of spermatogenesis and testicular atrophy with reduced testis size
|
• male mutants develop granulosa cell tumors of the testis by 9-13 weeks of age
|
• female mutants develop granulosa cell tumors by 6 months of age
|
• male mutants develop granulosa cell tumors of the testis by 9-13 weeks of age
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
granulosa cell tumor | DOID:2999 | J:186144 | ||
ovarian cancer | DOID:2394 |
OMIM:167000 OMIM:607893 |
J:186144 |
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• in addition to a normal male reproductive tract, XY mice developed uteri and oviducts
|
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• at 8 months of age, the number of corpus luteums is increased compared to in Inhbatm1Zuk/Inhbatm3Zuk mice
• the expression of a marker (Lhcgr) for healthy corpus luteums is increased relative to in Inhbatm1Zuk/Inhbatm3Zuk mice
|
• one follicle containing two oocytes at 3 months of age
|
• the number of litters produced by females is reduced 43% (0.51+/-0.05 litters per month compared 0.89+/-0.04 litters per month in Inhbatm1Zuk/Inhbatm3Zuk mice)
• however, there is no difference in the number of oocytes produced upon superovulation compared to Inhbatm1Zuk/Inhbatm3Zuk mice
|
• the number of pups per litter is decreased 33% relative (5.19+/-0.65 pups per litter compared to 7.78+/-0.48 pups per litter in wild-type mice)
|
• at 8 months of age, the number of corpus luteums is increased compared to in Inhbatm1Zuk/Inhbatm3Zuk mice
• the expression of a marker (Lhcgr) for healthy corpus luteums is increased relative to in Inhbatm1Zuk/Inhbatm3Zuk mice
|
• one follicle containing two oocytes at 3 months of age
|
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
N |
• mice exhibit normal male normal reproductive morphology
|
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• in superovulation experiments, mice ovulate half as many oocytes as wild-type mice
|
• in superovulation experiments, mice ovulate half as many oocytes as wild-type mice
|
• at 3 months, mice contain luteinizing follicles that encompass trapped oocytes unlike in wild-type mice
• at 8 months, mice exhibit more severe follicular abnormalities than at 3 moths with aberrant cumulus cell-oocytes unlike in wild-type mice
|
• at 3 months, fewer antral follicles are present compared to in wild-type ovaries
|
• at 3 months, a marker of follicular atresia accumulates unlike in wild-type ovaries
|
• treatment with pregnant mare serum gonadotropin (PMSG) induces only minimal cumulus expansion unlike in similarly treated wild-type mice and few cumulus cells attach to oocytes
• in culture, cumulus cells undergo disorganized and limited expansion in response to EGF compared to similarly treated wild-type cells
• in culture, cumulus cells stimulated by EGF detach from the cumulus oocyte complexes and attach to the culture plate leaving 18% of oocytes denuded unlike wild-type cells
|
• females exhibit reduced fertility and premature ovarian failure becoming infertile after 4 months of breeding unlike in wild-type mice
|
• at 8 months
|
• at 8 months
|
• females exhibit reduced fertility and premature ovarian failure becoming infertile after 4 months of breeding unlike in wild-type mice
|
• at 3 months, mice contain luteinizing follicles that encompass trapped oocytes unlike in wild-type mice
• at 8 months, mice exhibit more severe follicular abnormalities than at 3 moths with aberrant cumulus cell-oocytes unlike in wild-type mice
|
• at 3 months, fewer antral follicles are present compared to in wild-type ovaries
|
• at 3 months, a marker of follicular atresia accumulates unlike in wild-type ovaries
|
• treatment with pregnant mare serum gonadotropin (PMSG) induces only minimal cumulus expansion unlike in similarly treated wild-type mice and few cumulus cells attach to oocytes
• in culture, cumulus cells undergo disorganized and limited expansion in response to EGF compared to similarly treated wild-type cells
• in culture, cumulus cells stimulated by EGF detach from the cumulus oocyte complexes and attach to the culture plate leaving 18% of oocytes denuded unlike wild-type cells
|
• females exhibit reduced fertility and premature ovarian failure becoming infertile after 4 months of breeding unlike in wild-type mice
|
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
N |
• mice exhibit normal reproductive morphology and physiology
|
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• after 3 months of age, 100% of female mice have unilateral or bilateral ovarian tumors
|
• over 70% of female mice have metastic ovarian cancer by 1 year of age
|
• female mice become infertile after 3 to 4 months of breeding
|
• after 3 months of age, 100% of female mice have unilateral or bilateral ovarian tumors
|
• over 70% of female mice have metastic ovarian cancer by 1 year of age
|
• female mice become infertile after 3 to 4 months of breeding
|
• after 3 months of age, 100% of female mice have unilateral or bilateral ovarian tumors
|
• over 70% of female mice have metastic ovarian cancer by 1 year of age
|
• found in 50% of female mice over 9 months in age
|
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• no live sperm are found in epididymis
|
• testes show a 2.8-fold decrease in diploid cells and 4-fold increase in tetraploid cells relative to wild-type
|
• no lumen is observed
• Seroli cell nuclei show disorganization and dislocalization
|
• tubules show reduced diameters
|
• testes are normally descended but only attain 31.1% of that in wild-type males
|
• no mature or elongated spermatid or spermatozoa are found
|
• germ cell development stops at stage around secondary spermatocyte to round spermatid
|
• in three successive 2-week pairings with wild-type females, 14-week old males fail to impregnate the females; vaginal plugs were detected in females after mating
|
• no lumen is observed
• Seroli cell nuclei show disorganization and dislocalization
|
• tubules show reduced diameters
|
• testes are normally descended but only attain 31.1% of that in wild-type males
|
• significantly decreased relative to wild-type males
|
• no live sperm are found in epididymis
|
• testes show a 2.8-fold decrease in diploid cells and 4-fold increase in tetraploid cells relative to wild-type
|
• germ cell development stops at stage around secondary spermatocyte to round spermatid
|
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• superovulated mutant females show a significant reduction in numbers of oocytes collected from the oviducts compared to controls
|
• superovulated mutant females show a significant reduction in numbers of oocytes collected from the oviducts compared to controls
|
• ovaries of knockout animals often contain small follicles with luteinizing cells surrounding either oocytes or oocyte remnants
|
• some secondary stage follicles show oocytes without associated granulosa cells
|
• in knockout mice, there are fewer large antral follicles
|
• in knockout females, large follicle-like structures enclosing a trapped oocyte are observed
• in superovulated females, some follicles show oocytes lacking cumulus cells
|
• in superovualated females, half as many intact cumulus-oocyte complexes are recovered from large antral follicles after 44 hours compared to controls
• cumulus-oocyte complexes isolated from mutant females show reduced or absent cumulus expansion when cultured in the presence of serum and FSH
|
• cumulus-oocyte complexes isolated from mutant females may show absent cumulus expansion when cultured in the presence of serum and FSH
|
• some secondary stage follicles show oocytes without associated granulosa cells
|
• in knockout mice, there are more preantral follicles
|
• mutant females ovulate about half as much as wild-type
|
• null mice have an average of 1.3 pups per litter over a 6-month period, compared to 10.4 pups/litter for control Smad4tm1.1Rob/Smad4tm1Rob animals which is not different from wild-type litter size
|
• at 3 months of age, 25% of breeding females are infertile; by 6 months of age, 50% are infertile
|
• ovaries of knockout animals often contain small follicles with luteinizing cells surrounding either oocytes or oocyte remnants
|
• some secondary stage follicles show oocytes without associated granulosa cells
|
• in knockout mice, there are fewer large antral follicles
|
• in knockout females, large follicle-like structures enclosing a trapped oocyte are observed
• in superovulated females, some follicles show oocytes lacking cumulus cells
|
• in superovualated females, half as many intact cumulus-oocyte complexes are recovered from large antral follicles after 44 hours compared to controls
• cumulus-oocyte complexes isolated from mutant females show reduced or absent cumulus expansion when cultured in the presence of serum and FSH
|
• cumulus-oocyte complexes isolated from mutant females may show absent cumulus expansion when cultured in the presence of serum and FSH
|
• some secondary stage follicles show oocytes without associated granulosa cells
|
• in knockout mice, there are more preantral follicles
|
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• the majority of ovaries in 8 month old mice appeared hemorrhagic
|
• ovaries were histologically normal through 21 days of age
• defects became apparent after 3 months of age
|
• some mice developed Sertoli cell tubule-like structures, reminiscent of the ovarian tumors observed in mice inhibin-deficient mice, mice overexpressing follistatin and follicle stimulating hormone, mice lacking both estrogen receptors alpha and beta, and mice overexpressing anti-Mullerian hormone
|
• decreased numbers of antral follicles
|
• observed in 2 mice
|
• observed in 2 mice
|
N |
• circulating estradiol levels did not differ from those of controls
|
N |
• male mice were fertile
|
• the majority of ovaries in 8 month old mice appeared hemorrhagic
|
• ovaries were histologically normal through 21 days of age
• defects became apparent after 3 months of age
|
• some mice developed Sertoli cell tubule-like structures, reminiscent of the ovarian tumors observed in mice inhibin-deficient mice, mice overexpressing follistatin and follicle stimulating hormone, mice lacking both estrogen receptors alpha and beta, and mice overexpressing anti-Mullerian hormone
|
• decreased numbers of antral follicles
|
• observed in 2 mice
|
• impaired ovulation in response to human chorionic gonadotropin (hCG) only in mature adult mice (6 months of age)
• however, superovulation was normal in 3-week-old mice
|
• of 11 female experimental mice, 1 was completely infertile
|
• of 11 female experimental mice, 10 showed reduced fertility, yielding reduced litter number and size
|
• impaired fertilization only in mature adult mice (6 months of age)
• fertilization was normal in 3-week-old mice
|
• the majority of ovaries in 8 month old mice appeared hemorrhagic
|
Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB)), Gene Ontology (GO) |
||
Citing These Resources Funding Information Warranty Disclaimer, Privacy Notice, Licensing, & Copyright Send questions and comments to User Support. |
last database update 11/05/2024 MGI 6.24 |
|
|