Sertoli Cell-Specific Deletion of Hsp90aa1 Does Not Overtly Impair Male Fertility in Mice

The stress-inducible molecular chaperone HSP90α, encoded by Hsp90aa1, plays an essential role in male reproduction. Systemic Hsp90aa1 deficiency causes pachytene arrest, germ cell loss, and azoospermia. However, systemic models cannot distinguish effects originating in germ cells from those mediated by the testicular somatic microenvironment. Sertoli cells sustain germ cell development through physical support, nutrient supply and regulatory signaling. The function of HSP90α in Sertoli cells has previously been studied mainly in cultured cells, with a lack of in vivo evidence. To investigate its role in Sertoli cells, we generated Hsp90aa1flox/flox; Amhr2-Cre+ conditional knockout (CKO) mice. HSP90α was markedly reduced in Sertoli cell-enriched fractions from CKO testes, and testicular immunofluorescence showed reduced signal in Sertoli cell regions. Despite this reduction, CKO males remained fertile and showed no significant abnormalities in testicular morphology, spermatogenic progression, the measured sperm parameters, Sertoli cell counts, or the localization of the junction-associated proteins. However, total germ cell counts were modestly reduced in CKO testes, with the reduction primarily observed in spermatocytes. These findings indicate that Sertoli-cell Hsp90aa1 deletion is associated with a modest reduction in spermatocyte numbers but does not overtly impair male fertility under the conditions examined. The contrast with systemic Hsp90aa1 deficiency suggests that the requirement for HSP90α in male reproduction is cell type-specific.