17β‐Estradiol Inhibits Endoplasmic Reticulum Stress and Alleviates Pyroptosis via the NLRP3/Caspase‐1/GSDMD Axis in Sheep Theca Cells
Yahua Yang, Yue Yuan, Xiaona Ding, Pinshen Li, Rui Xiao, Chongfa Yang, Zhijie Zhao, Bingzhu Zhao, Hao Chen, Yang Li, Junyuan Ma, Chunjiang Dou, Shengdong HuoABSTRACT
17β‐Estradiol (E 2 ) is an important reproductive hormone and exhibits anti‐inflammatory properties. To explore the mechanism of estrogen in alleviating inflammation, we used theca cells (TCs) as a model cell type in this study. Lipopolysaccharide (LPS) was used to induce a cell injury model. Protein localization and expression in TCs were assessed by immunofluorescence and Western blotting, organelle morphology was examined by transmission electron microscopy; and target gene expression was analyzed by qRT‐PCR. The results showed that E 2 significantly enhanced the viability of TCs pretreated with LPS ( p < 0.05). E 2 treatment alleviated endoplasmic reticulum (ER) and mitochondrial damage. E 2 significantly decreased the expression of CHOP and P‐PERK/PERK, P‐IRE1α/IRE1α and ATF6 ( p < 0.05). E 2 inhibited pyroptosis via significantly downregulating the expression of GSDMD, NLRP3 and Cleaved caspase‐1 ( p < 0.05). Following the inhibition of ER stress by 4‐PBA, the expression levels of CHOP and GSDMD were significantly reduced in the E 2 + LPS + 4‐PBA group ( p < 0.05). In conclusion, E 2 relieved LPS‐induced ER stress and pyroptosis in sheep TCs via the CHOP/NLRP3/Caspase‐1/GSDMD pathway. This finding provides new insights into the role of estrogen in female reproductive health and suggests a potential therapeutic strategy for improving ovarian immune and reproductive function through the modulation of hormonal homeostasis.