Premium
Hormone regulates endometrial function via cooperation of endoplasmic reticulum stress and mTOR‐autophagy
Author(s) -
Yang Diqi,
Jiang Tingting,
Liu Jianguo,
Hong Jin,
Lin Pengfei,
Chen Huatao,
Zhou Dong,
Tang Keqiong,
Wang Aihua,
Jin Yaping
Publication year - 2018
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.26315
Subject(s) - endoplasmic reticulum , conceptus , unfolded protein response , autophagy , microbiology and biotechnology , pi3k/akt/mtor pathway , atf6 , medicine , endocrinology , gene knockdown , thapsigargin , chemistry , signal transduction , biology , apoptosis , biochemistry , fetus , pregnancy , genetics
In ruminant, the receptive endometrium and the elongation of the hatched blastocyst are required to complete the process of implantation. However, the mechanisms regulating goat endometrial function during the peri‐implantation period of pregnancy are still unclear. In this study, EECs were treated with progesterone, estradiol, and interferon‐tau (IFNT). We have found that endoplasmic reticulum (ER) stress was activated under hormones treatment. To identify the cellular mechanism of regulation of endometrial function, we investigated the effect of ER stress activator thapsigargin (TG) and inhibitor 4 phenyl butyric acid (4‐PBA) on EECs. We found that TG, which activated the three branches of UPR, increased the expression of genes associated with promoting conceptus elongation and cellular attachment, significantly up‐regulated the spheroid attachment rate and PGE 2 /PGF 2α ratio. 4‐PBA pre‐treatment inhibited UPR and inhibited promoting conceptus elongation and cellular attachment related genes, but the spheroid attachment rate and PGE 2 /PGF 2α ratio were not changed significantly. Moreover, knockdown of ATF6 via shATF6 promoted the conceptus elongation related genes, but increased the dissolution of the corpus luteum. Besides, blocking ATF6 attenuated autophagy by activating mammalian target of rapamycin (mTOR) pathway. Moreover, rapamycin (mTOR inhibitor) pre‐treatment inhibited the expression of promoting conceptus elongation and increased PGE 2 /PGF 2α ratio. Taken together, our study indicated that physiological level of ER stress may contribute to early pregnancy success, and ATF6 signaling pathway cooperated with autophagy to regulate endometrial function by modulating mTOR pathway.