Spermatogonial differentiation in juvenile spermatogonial depletion (jsd) mice with androgen receptor or follicle-stimulating hormone mutations.
The jsd mice experience a single wave of spermatogenesis, followed by an arrest of spermatogenesis because of a block in spermatogonial differentiation. Previous pharmacological and surgical studies have indicated that testosterone (T) and low scrotal temperatures but not FSH block spermatogonial differentiation in jsd mice. We sought to test these observations by genetic approaches by producing male jsd mutant mice with either defective androgen receptor (AR, Tfm mutation) or a deficiency of FSH (fshb(-/-)). In adult jsd-Tfm double-mutant mice, the tubule differentiation index was 95% compared with 14% in jsd littermates, suggesting that general ablation of AR function restored spermatogonial differentiation in jsd mice. The results indicated that this enhancement of differentiation was primarily a result of elevation of temperature caused by the cryptorchid position of the testis in jsd-Tfm double-mutant mice, which resulted from the lack of AR in the gubernaculum. The low levels of T were not a factor in the release of the spermatogonial differentiation block in the jsd-Tfm mice, but we were unable to determine whether inactivation of AR in the adult jsd testis had a direct effect on the restoration of spermatogonial differentiation because the elevated temperature bypassed the T-induced block in spermatogonial differentiation. Although spermatogonia were indeed present in adult jsd-fshb double-mutant mice and were capable of differentiation after androgen deprivation, these mice had a tubule differentiation index of 0%, ruling out the possibility that endogenous FSH inhibited spermatogonial differentiation in jsd mice. The results are consistent in support of the hypothesis that inhibition of spermatogonial differentiation in jsd mice is a result of T acting through the AR only at scrotal temperatures.
Shetty
Gunapala
G
Department of Experimental Radiation Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, 77030, USA. sgunapal@mdanderson.org
Weng
Connie C Y
CC
Porter
Karen L
KL
Zhang
Zhen
Z
Pakarinen
Pirjo
P
Kumar
T Rajendra
TR
Meistrich
Marvin L
ML
D000818:Animals; D002454:Cell Differentiation; D005260:Female; D005640:Follicle Stimulating Hormone / Q000235:genetics*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009154:Mutation; D011944:Receptors, Androgen / Q000235:genetics*; D020718:Ribonucleoproteins, Small Nucleolar / Q000235:genetics* / Q000502:physiology; D013093:Spermatogonia / Q000166:cytology* / Q000378:metabolism; D013737:Testis / Q000378:metabolism
D011944:Receptors, Androgen; D020718:Ribonucleoproteins, Small Nucleolar; C490705:Utp14b protein, mouse; D005640:Follicle Stimulating Hormone