Abstract
Corpus luteum (CL) is a transient endocrine tissue that produces progesterone for maintaining pregnancy in mammals. In addition, the regression of CL is necessary for the initiation of the estrous cycle. Extensive research has shown that the prostaglandin F2α (PGF2α) induces the regression of CL in ruminants. However, the mechanisms of endoplasmic reticulum (ER) stress and autophagy in the regression of goat CL induced by PGF2α are still unclear. In this study, ovaries of dioestrus goats and goats that were 3 months pregnant were collected to detect the location of the ER stress-related protein GRP78. The relationship between the different stages of the luteal phase of goat CL during the estrous cycle and changes in the expression of ER stress-related proteins and autophagy-related proteins was confirmed by western blot analysis. The results showed that both ER stress and autophagy were activated in the late luteal phase of the goat CL. To reveal the function of ER stress and autophagy in the CL regression process induced by PGF2α, we used 4-phenyl butyric acid (4-PBA) and chloroquine (CQ) for inhibiting ER stress and autophagy, respectively. Through the apoptotic rate detected by the flow cytometry and the expression of ER stress- and autophagy-related proteins detected by western blotting, we demonstrated that ER stress promoted goat luteal cell apoptosis and autophagy, and that apoptosis can be enhanced by the inhibition of autophagy. In addition, knockdown of EIF2S1, which blocked the PERK pathway activation, promoted apoptosis by reducing autophagy in goat luteal cells treated with PGF2α. In conclusion, our study indicates that ER stress promotes goat luteal cell apoptosis to regulate the regression of CL and activates autophagy to inhibit the goat luteal cell apoptosis via PERK signaling pathway.
Highlights
In mammals, the corpus luteum (CL) is an endocrine gland whose function and survival are limited in scope and time
According to the macroscopic appearance, LH receptor, and the expression of steroidogenic genes including STAR, 3β-hydroxysteroid dehydrogenase (3βHSD), and CYP19A1, which are genes that are expressed in different stages of the luteal phase of the goat CL, the luteal phase can be divided into three main groups
The expression of endoplasmic reticulum (ER) stress-related proteins glucose-regulated protein 78 (GRP78), unfolded protein response (UPR) sensors including phosphorylated-inositol-requiring enzyme 1α (IRE1), IRE1, phosphorylated-eukaryotic translation initiation factor 2 subunit 1 (EIF2S1), EIF2S1, activate transcription factor 4 (ATF4), cleaved activating transcription factor 6 (ATF6), autophagy-related protein light chain 3 (LC3), and apoptotic factor cleaved Caspase3 in the different stages of the luteal phase of goat CL were detected by western blot analysis
Summary
The corpus luteum (CL) is an endocrine gland whose function and survival are limited in scope and time. Follicular granulosa cells and theca cells divide and differentiate rapidly into luteal cells to develop CL in mammals (Caligioni, 2009). The function of luteal cells is regulated by steroidogenic enzymes such as the steroidogenic acute regulatory. ERS Regulates Goat CL Regression protein (STAR) and 3β-hydroxysteroid dehydrogenase (3βHSD) (Rekawiecki et al, 2008). If the egg does not fertilize, the CL regresses within a few days, allowing a new estrous cycle to begin (Jiemtaweeboon et al, 2011). The development and function of CL are crucial for maintaining pregnancy, and the regression of the CL is necessary for the initiation of the estrous cycle (Stocco et al, 2007; Lee et al, 2016)
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