FSH promotes immature porcine Sertoli cell proliferation by activating the CCR7/Ras-ERK signaling axis

Abstract

Follicle-stimulating hormone (FSH) is a major Sertoli cell mitogen that binds to the FSH-R receptor. Sertoli cells are indispensable for testis development and spermatogenesis. However, the regulatory mechanisms of FSH in immature Sertoli cell proliferation has not been determined, particularly in domestic animals. In the present study, we identified the regulatory mechanisms of FSH during immature porcine Sertoli cell proliferation. A transcriptome analysis revealed 114 differentially expressed genes that were induced by FSH treatment, which containing with 68 up-regulated and 46 down-regulated genes. These differentially expressed genes were enriched in multiple pathways, including the Ras signaling pathway. Knockdown of the CC-chemokine receptor 7 (CCR7) gene, which was up-regulated by FSH, inhibited cell cycle progression by arresting cells in the G1 phase, and reduced the cell proliferation and ERK1/2 phosphorylation. In addition, Kobe0065 inhibited Ras signaling in a similar manner as CCR7 knockdown. Furthermore, FSH abolished the effects of Ras signaling pathway inhibition and CCR7 knockdown. Collectively, FSH promotes immature porcine Sertoli cell proliferation by activating the CCR7/Ras-ERK signaling axis. Our results provide novel insights into the regulatory mechanism of FSH in porcine testis development and spermatogenesis by deciding the fate of immature porcine Sertoli cells.