Estrogen Regulates Ca<sup>2+</sup> to Promote Mitochondrial Function Through G-Protein-Coupled Estrogen Receptors During Oocyte Maturation

Estrogen is a steroid hormone that plays a key role in regulating many physiological processes, such as follicle activation and development and oocyte maturation in mammals. Ca<sup>2+</sup> is crucial in oogenesis, oocyte maturation, ovulation, and fertilization. However, the mechanism b...

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Main Authors: Qingyang Liu, Jingmei Li, Yanxue Li, Ming Cheng, Hui Zhang, Baohua Ma
Format: Article
Language:English
Published: MDPI AG 2024-11-01
Series:Biomolecules
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Online Access:https://www.mdpi.com/2218-273X/14/11/1430
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author Qingyang Liu
Jingmei Li
Yanxue Li
Ming Cheng
Hui Zhang
Baohua Ma
author_facet Qingyang Liu
Jingmei Li
Yanxue Li
Ming Cheng
Hui Zhang
Baohua Ma
author_sort Qingyang Liu
collection DOAJ
description Estrogen is a steroid hormone that plays a key role in regulating many physiological processes, such as follicle activation and development and oocyte maturation in mammals. Ca<sup>2+</sup> is crucial in oogenesis, oocyte maturation, ovulation, and fertilization. However, the mechanism by which estrogen regulates Ca<sup>2+</sup> during oocyte maturation in mice has not been reported. This study revealed that Ca<sup>2+</sup> levels in oocytes significantly increase during the 4–12 h period in vitro. Oocytes treated with 0.1 µM estrogen and 1 µM G1, a G-protein-coupled estrogen receptor (GPER) agonist, showed significantly increased Ca<sup>2+</sup> levels, while treatment with 1 µM G15, an antagonist of GPER, significantly decreased Ca<sup>2+</sup> levels. Notably, estrogen regulates Ca<sup>2+</sup> in oocytes through the GPER pathway and promotes the expression of the Ca<sup>2+</sup>-producing protein EPAC1. In addition, estrogen alleviates the inhibitory effect of the Ca<sup>2+</sup> chelator BAPTA-AM during oocyte maturation by promoting Ca<sup>2+</sup> production. Furthermore, estrogen can promote the expression of the mitochondrial generation-associated protein SIRT1 through the GPER pathway, alleviate mitochondrial oxidative damage caused by BAPTA-AM, and restore the mitochondrial membrane potential level. Collectively, this study demonstrates that estrogen can regulate Ca<sup>2+</sup> through the GPER-EPAC1 pathway and promote the expression of SIRT1, which promotes oocyte mitochondrial function during oocyte maturation.
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spelling doaj-art-c8fca698c40d46518d8dc9b730f3d32d2025-08-20T02:28:07ZengMDPI AGBiomolecules2218-273X2024-11-011411143010.3390/biom14111430Estrogen Regulates Ca<sup>2+</sup> to Promote Mitochondrial Function Through G-Protein-Coupled Estrogen Receptors During Oocyte MaturationQingyang Liu0Jingmei Li1Yanxue Li2Ming Cheng3Hui Zhang4Baohua Ma5College of Veterinary Medicine, Northwest A&F University, Yangling 712100, ChinaCollege of Veterinary Medicine, Northwest A&F University, Yangling 712100, ChinaCollege of Veterinary Medicine, Northwest A&F University, Yangling 712100, ChinaCollege of Veterinary Medicine, Northwest A&F University, Yangling 712100, ChinaCollege of Veterinary Medicine, Northwest A&F University, Yangling 712100, ChinaCollege of Veterinary Medicine, Northwest A&F University, Yangling 712100, ChinaEstrogen is a steroid hormone that plays a key role in regulating many physiological processes, such as follicle activation and development and oocyte maturation in mammals. Ca<sup>2+</sup> is crucial in oogenesis, oocyte maturation, ovulation, and fertilization. However, the mechanism by which estrogen regulates Ca<sup>2+</sup> during oocyte maturation in mice has not been reported. This study revealed that Ca<sup>2+</sup> levels in oocytes significantly increase during the 4–12 h period in vitro. Oocytes treated with 0.1 µM estrogen and 1 µM G1, a G-protein-coupled estrogen receptor (GPER) agonist, showed significantly increased Ca<sup>2+</sup> levels, while treatment with 1 µM G15, an antagonist of GPER, significantly decreased Ca<sup>2+</sup> levels. Notably, estrogen regulates Ca<sup>2+</sup> in oocytes through the GPER pathway and promotes the expression of the Ca<sup>2+</sup>-producing protein EPAC1. In addition, estrogen alleviates the inhibitory effect of the Ca<sup>2+</sup> chelator BAPTA-AM during oocyte maturation by promoting Ca<sup>2+</sup> production. Furthermore, estrogen can promote the expression of the mitochondrial generation-associated protein SIRT1 through the GPER pathway, alleviate mitochondrial oxidative damage caused by BAPTA-AM, and restore the mitochondrial membrane potential level. Collectively, this study demonstrates that estrogen can regulate Ca<sup>2+</sup> through the GPER-EPAC1 pathway and promote the expression of SIRT1, which promotes oocyte mitochondrial function during oocyte maturation.https://www.mdpi.com/2218-273X/14/11/1430estrogencalciumoocyte maturationmice
spellingShingle Qingyang Liu
Jingmei Li
Yanxue Li
Ming Cheng
Hui Zhang
Baohua Ma
Estrogen Regulates Ca<sup>2+</sup> to Promote Mitochondrial Function Through G-Protein-Coupled Estrogen Receptors During Oocyte Maturation
Biomolecules
estrogen
calcium
oocyte maturation
mice
title Estrogen Regulates Ca<sup>2+</sup> to Promote Mitochondrial Function Through G-Protein-Coupled Estrogen Receptors During Oocyte Maturation
title_full Estrogen Regulates Ca<sup>2+</sup> to Promote Mitochondrial Function Through G-Protein-Coupled Estrogen Receptors During Oocyte Maturation
title_fullStr Estrogen Regulates Ca<sup>2+</sup> to Promote Mitochondrial Function Through G-Protein-Coupled Estrogen Receptors During Oocyte Maturation
title_full_unstemmed Estrogen Regulates Ca<sup>2+</sup> to Promote Mitochondrial Function Through G-Protein-Coupled Estrogen Receptors During Oocyte Maturation
title_short Estrogen Regulates Ca<sup>2+</sup> to Promote Mitochondrial Function Through G-Protein-Coupled Estrogen Receptors During Oocyte Maturation
title_sort estrogen regulates ca sup 2 sup to promote mitochondrial function through g protein coupled estrogen receptors during oocyte maturation
topic estrogen
calcium
oocyte maturation
mice
url https://www.mdpi.com/2218-273X/14/11/1430
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AT jingmeili estrogenregulatescasup2suptopromotemitochondrialfunctionthroughgproteincoupledestrogenreceptorsduringoocytematuration
AT yanxueli estrogenregulatescasup2suptopromotemitochondrialfunctionthroughgproteincoupledestrogenreceptorsduringoocytematuration
AT mingcheng estrogenregulatescasup2suptopromotemitochondrialfunctionthroughgproteincoupledestrogenreceptorsduringoocytematuration
AT huizhang estrogenregulatescasup2suptopromotemitochondrialfunctionthroughgproteincoupledestrogenreceptorsduringoocytematuration
AT baohuama estrogenregulatescasup2suptopromotemitochondrialfunctionthroughgproteincoupledestrogenreceptorsduringoocytematuration