Reduced mitotic activity and increased apoptosis of fetal sertoli cells in rat hypogonadic (hgn/hgn) testes.
Sterility in male hypogonadic (hgn/hgn) rats results from congenital testicular dysplasia caused by a single recessive gene hgn on rat chromosome 10. We recently identified an insertion mutation in the Spag5/astrin gene of hgn/hgn rats that may cause defective proliferation of immature Sertoli cells in the postnatal hgn/hgn testis. Since the pathological alterations were present in the testes at birth, we examined the involvement of defective mitosis and apoptotic cell death in embryonic development of hgn/hgn testes. Testicular hypoplasia was apparent at embryonic day (ED) 18.5. Immunostaining of hgn/hgn testes at ED 21.5 with antibody to GATA-4, which is specific for fetal Sertoli cells in the seminiferous cords, showed that the significant decrease in the number of fetal Sertoli cells was accompanied by a two fold increase in their mitotic index and abnormal mitosis and apoptosis. Prior to this, we observed a decrease in the number of BrdU-labeled cells, an increase in the number of TUNEL-positive apoptotic cells, and presence of MIS-positive apoptotic cells in hgn/hgn testes on ED 17.5 and 18.5. These results suggest that the Spag5 mutation may cause a reduction in mitotic activity and an increase in apoptosis of fetal Sertoli cells in hgn/hgn testes.
Yagi
Mio
M
Laboratory of Veterinary Physiology, Nippon Veterinary and Life Science University, Japan.
Takenaka
Motoo
M
Suzuki
Katsushi
K
Suzuki
Hiroetsu
H
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology*; D047108:Embryonic Development / Q000502:physiology*; D050991:GATA4 Transcription Factor / Q000378:metabolism; D007006:Hypogonadism / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D007150:Immunohistochemistry; D008297:Male; D008938:Mitosis / Q000502:physiology*; D051381:Rats; D011914:Rats, Inbred BN; D012708:Sertoli Cells / Q000502:physiology; D013737:Testis / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*
D002352:Carrier Proteins; D050991:GATA4 Transcription Factor; C436025:Spag5 protein, rat