1α,25(OH)2D3 improves 17β-estradiol secretion and potentially alleviates endoplasmic reticulum stress in muskrat granulosa cells.

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.