growth/size/body
• at the onset of puberty, females are significantly lighter than wild-type controls
|
reproductive system
N |
• at 8 weeks of age, male mice exhibit normal testis and seminal vesicle weight to body weight ratio
|
• although early ovarian follicles develop normally, the number of corpora lutea per ovary is significantly lower than in wild-type females
• however, corpora lutea formation is rescued by exogenous gonadotropin injection
|
• wet ovary weight to body weight ratio is significantly decreased at 8 weeks of age
|
• expression of Cyp11a1, which is essential to the level of sex hormones, is significantly decreased in the ovary
• however, ovarian expression of Cyp19a1 and Cyp17a1, encoding enzymes involved in estradiol and testosterone synthesis, is normal
|
• uterus weight to body weight ratio is significantly decreased at 8 weeks of age
|
• vaginal opening occurs 5 days later (P28) than in wild-type females (P23)
|
• during natural ovulation, only 2 oocytes were collected from the oviducts of 20 females with a visible plug
• however, ovulation is rescued by exogenous gonadotropin injection
|
• females display irregular estrous cycles
|
• females spend significantly more time in diestrus
|
short estrus
(
J:324059
)
• females spend significantly less time in estrus
|
• females spend significantly less time in metestrus
|
• 23 of the 25 virgin 8-week-old females tested failed to conceive within 1 month of mating and were defined as sterile
|
• 2 of the 25 virgin 8-week-old females tested gave birth to 2 pups each but did not become subsequently pregnant
|
• females produce a mean litter size of 2 pups/litter versus 7.6 pups/litter in wild-type females
|
• 66.7% of 8-week-old males were still fertile
|
• during natural ovulation, only 2 oocytes were collected from the oviducts of 20 females with a visible plug and no 2-cell embryos were found the following day
• however, the number of 2-cell embryos obtained is restored to nearly wild-type levels after exogenous gonadotropin injection
|
nervous system
• gonadotropin releasing hormone receptor (GnRHR)-immunoreactivity is significantly increased in the pituitary
|
• females show impaired pituitary hormone secretion, especially LH released
|
homeostasis/metabolism
N |
• female mice show normal serum follicle-stimulating hormone (FSH), testosterone and estradiol (E2) levels
|
• females show a significant reduction in serum luteinizing hormone (LH) levels
• despite normal GnRH responsiveness in the pituitary, serum LH levels remain markedly below wild-type levels after i.p. injection of exogenous GnRH
• after ovariectomy, females fail to show a significant rise in serum LH levels unlike ovariectomized wild-type females, indicating a block in LH secretion
• however, rise in serum FSH levels is relatively normal after ovariectomy
|
• females show a significant reduction in serum progesterone (P4) levels
|
• expression of Cyp11a1, which is essential to the level of sex hormones, is significantly decreased in the ovary
• however, ovarian expression of Cyp19a1 and Cyp17a1, encoding enzymes involved in estradiol and testosterone synthesis, is normal
|
• LH protein levels and immunoreactivity are significantly increased in the pituitary
|
behavior/neurological
• females show a significant lower mating frequency than wild-type females
|
endocrine/exocrine glands
• although early ovarian follicles develop normally, the number of corpora lutea per ovary is significantly lower than in wild-type females
• however, corpora lutea formation is rescued by exogenous gonadotropin injection
|
• wet ovary weight to body weight ratio is significantly decreased at 8 weeks of age
|
• gonadotropin releasing hormone receptor (GnRHR)-immunoreactivity is significantly increased in the pituitary
|
• females show impaired pituitary hormone secretion, especially LH released
|
• expression of Cyp11a1, which is essential to the level of sex hormones, is significantly decreased in the ovary
• however, ovarian expression of Cyp19a1 and Cyp17a1, encoding enzymes involved in estradiol and testosterone synthesis, is normal
|
cellular
• females show abnormal expression of several proteins involved in vesicular transport in the pituitary
|
• females show abnormal expression of several proteins involved in exocytosis in the pituitary
|