All Phenotypes Tsks<em1Osb> MGI Mouse

reproductive system phenotype ( J:337844 )

N	• despite infertility, male mice exhibit normal testis gross morphology and testicular weight relative to control males

increased male germ cell apoptosis ( J:337844 )

• cauda epididymal spermatozoa with excess residual cytoplasm (ERC) express cleaved caspase-3, indicating an increased apoptotic response

decreased sperm progressive motility ( J:337844 )

• progressive sperm rate (%) is significantly lower than that of control males

asthenozoospermia ( J:337844 )

• sperm motility (%) is significantly lower than that of control males

• however, propidium iodide staining revealed a normal live sperm rate (%), suggesting that the extremely low motility observed is not due to sperm death

abnormal spermatogenesis ( J:337844 )

• many mature sperm heads are abnormally observed in stage IX seminiferous tubules

• in stage VIII tubules, testis appears to be crowded with a large number of sperm heads present in the lumen, unlike in control testis where spermatozoa are in a row in the lumen of the testis

teratozoospermia ( J:337844 )

• >80% of cauda epididymal spermatozoa show abnormalities in the sperm midpiece and/or head shape

abnormal sperm midpiece morphology ( J:337844 )

• SEM analysis revealed abnormal mitochondrial loss in the sperm midpiece

abnormal sperm mitochondrial sheath morphology ( J:337844 )

• SEM analysis revealed abnormal mitochondrial alignment

abnormal sperm head morphology ( J:337844 )

• SEM analysis revealed abnormal sperm head shape

abnormal spermatid morphology ( J:337844 )

• at stage VIII, spermatids lack the thin spermatid stalk that normally connects spermatids and the cytoplasmic lobe in control testes

• however, TEM analysis showed normal axonemes in step 16 spermatids

abnormal spermiation ( J:337844 )

• after release from Sertoli cells, spermatozoa show an abundance of contents inside their cytoplasm near the midpiece; cytoplasm contains RNA, mitochondria, vacuoles, lipid droplets, lysosomes and multiple vesicular bodies, which should have been separated from the cytoplasm as residual bodies

• Toluidine blue staining revealed dark blue cytoplasmic spots in the lumens of seminiferous tubules around stages VII-VIII, indicating excess residual cytoplasm (ERC)

• no spermatid stalks are detected in the tubules at stage VIII and the contents that should be in the cytoplasmic lobe are located near the flagellum

• spermatozoa with ERC show incomplete membrane and/or substances with high electron density whereas those without ERC display a few abnormalities

• further analysis showed that reticulated body (RB) and chromatoid body remnant (CR) two types of nuage, that is, membraneless organelles composed of electron-dense material are not formed; due to lack of TSKS-derived nuage, cytoplasmic contents cannot be eliminated from spermatid cytoplasm resulting in ERC

male infertility ( J:337844 )

• male mice fail to produce pups when mated with wild-type females

• however, male infertility can be rescued with intracytoplasmic sperm injection (ICSI)

decreased fertilization frequency ( J:337844 )

• in vitro fertilization assays showed a severe reduction in the fertilizing ability of spermatozoa when cumulus-intact, cumulus-free or zona-free oocytes are used

• however, after ICSI, 18.6% of oocytes microinjected with mutant spermatozoa were successfully activated and reached the 2-cell stage and 4 viable normal pups were obtained after embryo transfer