Prostaglandin F2α Induces Goat Corpus Luteum Regression via Endoplasmic Reticulum Stress and Autophagy

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...

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Main Authors: Xin Wen, Lu Liu, Shanshan Li, Pengfei Lin, Huatao Chen, Dong Zhou, Keqiong Tang, Aihua Wang, Yaping Jin
Format: Article
Language:English
Published: Frontiers Media S.A. 2020-09-01
Series:Frontiers in Physiology
Subjects:
Online Access:https://www.frontiersin.org/article/10.3389/fphys.2020.00868/full
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author Xin Wen
Lu Liu
Shanshan Li
Pengfei Lin
Huatao Chen
Huatao Chen
Dong Zhou
Dong Zhou
Keqiong Tang
Keqiong Tang
Aihua Wang
Aihua Wang
Yaping Jin
Yaping Jin
author_facet Xin Wen
Lu Liu
Shanshan Li
Pengfei Lin
Huatao Chen
Huatao Chen
Dong Zhou
Dong Zhou
Keqiong Tang
Keqiong Tang
Aihua Wang
Aihua Wang
Yaping Jin
Yaping Jin
author_sort Xin Wen
collection DOAJ
description 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.
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spelling doaj.art-de3b0d675ce147c4bb0cd6a99be967912022-12-21T20:22:19ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2020-09-011110.3389/fphys.2020.00868543277Prostaglandin F2α Induces Goat Corpus Luteum Regression via Endoplasmic Reticulum Stress and AutophagyXin Wen0Lu Liu1Shanshan Li2Pengfei Lin3Huatao Chen4Huatao Chen5Dong Zhou6Dong Zhou7Keqiong Tang8Keqiong Tang9Aihua Wang10Aihua Wang11Yaping Jin12Yaping Jin13Key Laboratory of Animal Biotechnology of the Ministry of Agriculture, College of Veterinary Medicine, Northwest A&F University, Yangling, ChinaKey Laboratory of Animal Biotechnology of the Ministry of Agriculture, College of Veterinary Medicine, Northwest A&F University, Yangling, ChinaKey Laboratory of Animal Biotechnology of the Ministry of Agriculture, College of Veterinary Medicine, Northwest A&F University, Yangling, ChinaKey Laboratory of Animal Biotechnology of the Ministry of Agriculture, College of Veterinary Medicine, Northwest A&F University, Yangling, ChinaKey Laboratory of Animal Biotechnology of the Ministry of Agriculture, College of Veterinary Medicine, Northwest A&F University, Yangling, ChinaDepartment of Clinical Veterinary Medicine, College of Veterinary Medicine, Northwest A&F University, Shaanxi, ChinaKey Laboratory of Animal Biotechnology of the Ministry of Agriculture, College of Veterinary Medicine, Northwest A&F University, Yangling, ChinaDepartment of Clinical Veterinary Medicine, College of Veterinary Medicine, Northwest A&F University, Shaanxi, ChinaKey Laboratory of Animal Biotechnology of the Ministry of Agriculture, College of Veterinary Medicine, Northwest A&F University, Yangling, ChinaDepartment of Clinical Veterinary Medicine, College of Veterinary Medicine, Northwest A&F University, Shaanxi, ChinaKey Laboratory of Animal Biotechnology of the Ministry of Agriculture, College of Veterinary Medicine, Northwest A&F University, Yangling, ChinaDepartment of Preventive Veterinary Medicine, College of Veterinary Medicine, Northwest A&F University, Shaanxi, ChinaKey Laboratory of Animal Biotechnology of the Ministry of Agriculture, College of Veterinary Medicine, Northwest A&F University, Yangling, ChinaDepartment of Clinical Veterinary Medicine, College of Veterinary Medicine, Northwest A&F University, Shaanxi, ChinaCorpus 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.https://www.frontiersin.org/article/10.3389/fphys.2020.00868/fullcorpus luteum regressionER stressautophagyprostaglandin F2αEIF2S1PERK
spellingShingle Xin Wen
Lu Liu
Shanshan Li
Pengfei Lin
Huatao Chen
Huatao Chen
Dong Zhou
Dong Zhou
Keqiong Tang
Keqiong Tang
Aihua Wang
Aihua Wang
Yaping Jin
Yaping Jin
Prostaglandin F2α Induces Goat Corpus Luteum Regression via Endoplasmic Reticulum Stress and Autophagy
Frontiers in Physiology
corpus luteum regression
ER stress
autophagy
prostaglandin F2α
EIF2S1
PERK
title Prostaglandin F2α Induces Goat Corpus Luteum Regression via Endoplasmic Reticulum Stress and Autophagy
title_full Prostaglandin F2α Induces Goat Corpus Luteum Regression via Endoplasmic Reticulum Stress and Autophagy
title_fullStr Prostaglandin F2α Induces Goat Corpus Luteum Regression via Endoplasmic Reticulum Stress and Autophagy
title_full_unstemmed Prostaglandin F2α Induces Goat Corpus Luteum Regression via Endoplasmic Reticulum Stress and Autophagy
title_short Prostaglandin F2α Induces Goat Corpus Luteum Regression via Endoplasmic Reticulum Stress and Autophagy
title_sort prostaglandin f2α induces goat corpus luteum regression via endoplasmic reticulum stress and autophagy
topic corpus luteum regression
ER stress
autophagy
prostaglandin F2α
EIF2S1
PERK
url https://www.frontiersin.org/article/10.3389/fphys.2020.00868/full
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