Abstract

Vitamin D₃ plays an essential regulatory role in female reproduction. However, the studies on the correlation between vitamin D₃ and muskrat reproduction are limited. This study aims to determine the role of the active form of vitamin D₃, 1α,25-dihydroxytamin D₃ [1α,25(OH)₂D₃], on muskrat ovarian granulosa cells (MGCs). The results showed that vitamin D receptor (VDR) was prominently localized in MGCs and 1α,25(OH)₂D₃ supplementation increased VDR signaling of MGCs. Meanwhile, 10?nM of 1α,25(OH)₂D₃ stimulated MGCs to secrete 17β-estradiol and enhanced the mRNA expression of steroidogenic enzymes. 1α,25(OH)₂D₃ also remarkably down-regulated MGCs endoplasmic reticulum stress according to the expression of GRP78, p-PERK, ATF4, and CHOP. In addition, RNA-seq analysis revealed that 10?nM of 1α,25(OH)₂D₃ activated the PI3K/Akt/mTOR and TNF pathways that contributed to the inhibition of MGCs apoptosis. Taken together, these findings suggest that 1α,25(OH)₂D₃-induced VDR signaling improves 17β-estradiol secretion and potentially alleviate MGCs endoplasmic reticulum stress through the PERK-ATF4-CHOP pathway.