Protective role of RGS2 in PM2.5-induced ovarian injury in rats: Modulation of Gq/11 signaling to maintain granulosa cell [Ca2 + ]i stability

Fine particulate matter (PM2.5) is toxic to reproduction and can cause a range of reproductive disorders. However, the mechanisms underlying female reproductive impairment due to PM2.5 exposure are unclear. In this study, we aimed to investigate the effects of PM2.5 on rat ovaries and the underlying...

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Main Authors: Zhenhua Ma, Xiaohui Du, Cuizhu Zhao, Yize Sun, Yunna Jia, Xiaojun Liang, Xiuzhen Yu, Yunhang Gao
Format: Article
Language:English
Published: Elsevier 2025-09-01
Series:Ecotoxicology and Environmental Safety
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Online Access:http://www.sciencedirect.com/science/article/pii/S0147651325008826
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author Zhenhua Ma
Xiaohui Du
Cuizhu Zhao
Yize Sun
Yunna Jia
Xiaojun Liang
Xiuzhen Yu
Yunhang Gao
author_facet Zhenhua Ma
Xiaohui Du
Cuizhu Zhao
Yize Sun
Yunna Jia
Xiaojun Liang
Xiuzhen Yu
Yunhang Gao
author_sort Zhenhua Ma
collection DOAJ
description Fine particulate matter (PM2.5) is toxic to reproduction and can cause a range of reproductive disorders. However, the mechanisms underlying female reproductive impairment due to PM2.5 exposure are unclear. In this study, we aimed to investigate the effects of PM2.5 on rat ovaries and the underlying molecular mechanisms. Animal models showed that PM2.5 exposure induced abnormal ovarian function and disturbed ovarian-related hormone homeostasis in rats, significantly increasing the proportion of follicular atresia. This process was accompanied by ovarian inflammation, oxidative stress, apoptosis, and damage to the intracellular calcium pool (endoplasmic reticulum). Regulators of G protein signaling (RGS) are thought to play an important role in ovarian physiology. We found abnormal expressed of RGS2 in PM2.5-induced ovarian damage. Overexpression of RGS2 via adeno-associated virus type 2/9 (AAV2/9) attenuated PM2.5-induced ovarian damage in rats. In addition, rat ovarian granulosa cells were extracted. In vitro experiments showed that RGS2 overexpression attenuated the harmful effects of PM2.5 on ovarian granulosa cells. In particular, RGS2 inhibited PM2.5-induced [Ca2+]i disturbances and the signaling of two G proteins (Gnaq, Gna11), and reduced the expression levels of PLCβ and IP3R. This process effectively maintained the stability of [Ca2+]i and ATP levels in ovarian granulosa cells. These data highlight the protective role of RGS2 in PM2.5-induced ovarian damage and provide new insights into the prevention and treatment of PM2.5-induced ovarian disease.
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spelling doaj-art-95a5133503404e40b59a5c2dee6119be2025-08-20T03:41:26ZengElsevierEcotoxicology and Environmental Safety0147-65132025-09-0130211853710.1016/j.ecoenv.2025.118537Protective role of RGS2 in PM2.5-induced ovarian injury in rats: Modulation of Gq/11 signaling to maintain granulosa cell [Ca2 + ]i stabilityZhenhua Ma0Xiaohui Du1Cuizhu Zhao2Yize Sun3Yunna Jia4Xiaojun Liang5Xiuzhen Yu6Yunhang Gao7College of Animal Science and Technology, Jilin Agricultural University, Changchun 130118, ChinaCollege of Animal Science and Technology, Jilin Agricultural University, Changchun 130118, ChinaCollege of Animal Science and Technology, Jilin Agricultural University, Changchun 130118, ChinaCollege of Animal Science and Technology, Jilin Agricultural University, Changchun 130118, ChinaCollege of Animal Science and Technology, Jilin Agricultural University, Changchun 130118, ChinaInstitute of Animal Science, Ningxia Academy of Agriculture and Forestry, Yinchuan 750002, ChinaInstitute of Agricultural Mechanization, Xinjiang Academy of Agricultural Sciences, Wulumuqi 830091, China; Corresponding authors.College of Animal Science and Technology, Jilin Agricultural University, Changchun 130118, China; Corresponding authors.Fine particulate matter (PM2.5) is toxic to reproduction and can cause a range of reproductive disorders. However, the mechanisms underlying female reproductive impairment due to PM2.5 exposure are unclear. In this study, we aimed to investigate the effects of PM2.5 on rat ovaries and the underlying molecular mechanisms. Animal models showed that PM2.5 exposure induced abnormal ovarian function and disturbed ovarian-related hormone homeostasis in rats, significantly increasing the proportion of follicular atresia. This process was accompanied by ovarian inflammation, oxidative stress, apoptosis, and damage to the intracellular calcium pool (endoplasmic reticulum). Regulators of G protein signaling (RGS) are thought to play an important role in ovarian physiology. We found abnormal expressed of RGS2 in PM2.5-induced ovarian damage. Overexpression of RGS2 via adeno-associated virus type 2/9 (AAV2/9) attenuated PM2.5-induced ovarian damage in rats. In addition, rat ovarian granulosa cells were extracted. In vitro experiments showed that RGS2 overexpression attenuated the harmful effects of PM2.5 on ovarian granulosa cells. In particular, RGS2 inhibited PM2.5-induced [Ca2+]i disturbances and the signaling of two G proteins (Gnaq, Gna11), and reduced the expression levels of PLCβ and IP3R. This process effectively maintained the stability of [Ca2+]i and ATP levels in ovarian granulosa cells. These data highlight the protective role of RGS2 in PM2.5-induced ovarian damage and provide new insights into the prevention and treatment of PM2.5-induced ovarian disease.http://www.sciencedirect.com/science/article/pii/S0147651325008826PM2.5Premature ovarian failureRegulator of G protein signaling 2Ovarian granulosa cellsIntracellular Ca2+Gq/11
spellingShingle Zhenhua Ma
Xiaohui Du
Cuizhu Zhao
Yize Sun
Yunna Jia
Xiaojun Liang
Xiuzhen Yu
Yunhang Gao
Protective role of RGS2 in PM2.5-induced ovarian injury in rats: Modulation of Gq/11 signaling to maintain granulosa cell [Ca2 + ]i stability
Ecotoxicology and Environmental Safety
PM2.5
Premature ovarian failure
Regulator of G protein signaling 2
Ovarian granulosa cells
Intracellular Ca2+
Gq/11
title Protective role of RGS2 in PM2.5-induced ovarian injury in rats: Modulation of Gq/11 signaling to maintain granulosa cell [Ca2 + ]i stability
title_full Protective role of RGS2 in PM2.5-induced ovarian injury in rats: Modulation of Gq/11 signaling to maintain granulosa cell [Ca2 + ]i stability
title_fullStr Protective role of RGS2 in PM2.5-induced ovarian injury in rats: Modulation of Gq/11 signaling to maintain granulosa cell [Ca2 + ]i stability
title_full_unstemmed Protective role of RGS2 in PM2.5-induced ovarian injury in rats: Modulation of Gq/11 signaling to maintain granulosa cell [Ca2 + ]i stability
title_short Protective role of RGS2 in PM2.5-induced ovarian injury in rats: Modulation of Gq/11 signaling to maintain granulosa cell [Ca2 + ]i stability
title_sort protective role of rgs2 in pm2 5 induced ovarian injury in rats modulation of gq 11 signaling to maintain granulosa cell ca2  i stability
topic PM2.5
Premature ovarian failure
Regulator of G protein signaling 2
Ovarian granulosa cells
Intracellular Ca2+
Gq/11
url http://www.sciencedirect.com/science/article/pii/S0147651325008826
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