Follicle-stimulating hormone promotes immature Sertoli cells proliferation via the Wnt/β-catenin signaling pathway in dairy goats

Sertoli cells (SC) are the pivotal somatic cells within the testicular microenvironment and are responsible for supporting and guiding the development of male germ cells throughout spermatogenesis. The size of the SC population is a key determinant of spermatogenic efficiency and success. Although FSH is well-established as a crucial regulator of reproduction, its specific effects and underlying molecular mechanisms in immature SC of dairy goats remain unclear. This study was designed to address this knowledge gap. We first delineated the critical period for SC proliferation in dairy goats. In vitro experiments demonstrated that treatment with 1 IU/mL FSH for 24 h significantly upregulated the expression of proliferation markers (PCNA, Ki-67) and cell cycle regulators (CDK1, CDK2, CDK4, CDK6) and enhanced the secretion of key cytokines (ABP, GDNF, SCF). Transcriptome analysis revealed that differentially expressed genes were enriched in signaling pathways including the Wnt pathway. Subsequent investigations confirmed that FSH activates the Wnt pathway and upregulates its downstream target genes. Crucially, pharmacological inhibition of the Wnt pathway markedly attenuated the pro-proliferative effect of FSH. Collectively, these findings provide the first ruminant evidence that FSH requires the Wnt/β-catenin cascade to expand the immature SC population. This species-specific regulatory feature may inform breeding strategies in dairy goats.