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

Vitamin D plays an essential regulatory role in female reproduction. However, the studies on the correlation between vitamin D and muskrat reproduction are limited. This study aims to determine the role of the active form of vitamin D, 1α,25-dihydroxytamin D [1α,25(OH)D], on muskrat ovarian granulosa cells (MGCs). The results showed that vitamin D receptor (VDR) was prominently localized in MGCs and 1α,25(OH)D supplementation increased VDR signaling of MGCs. Meanwhile, 10 nM of 1α,25(OH)D stimulated MGCs to secrete 17β-estradiol and enhanced the mRNA expression of steroidogenic enzymes. 1α,25(OH)D 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)D 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)D-induced VDR signaling improves 17β-estradiol secretion and potentially alleviate MGCs endoplasmic reticulum stress through the PERK-ATF4-CHOP pathway.