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Boron Attenuates Heat Stress–Induced Apoptosis by Inhibiting Endoplasmic Reticulum Stress in Mouse Granulosa Cells

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Abstract

Heat stress–induced apoptosis in granulosa cells is mediated by multiple apoptotic signaling pathways, including endoplasmic reticulum (ER) stress. Boron is a naturally occurring trace element with several cytoprotective properties. Nonetheless, the molecular mechanisms involved in the protective functions of boron in granulosa cells undergoing apoptosis caused by heat stress (HS) remain unclear. In this study, we investigated the role of boric acid, a predominant chemical form of boron, in HS-induced apoptotic damage in mouse granulosa cells (mGCs) and explored the underlying mechanisms. We found that HS treatment suppressed cell viability; increased the apoptotic rate of cells; potentiated the activity of caspase-3, a key player in the caspase-mediated apoptotic signaling pathway; and activated ER stress markers, including glucose-regulated protein 78 (GRP78) and CCAAT/enhancer-binding protein (C/EBP) homologous protein (CHOP) in mGCs. However, boric acid treatment effectively alleviated the effects of both HS-induced and thapsigargin (an ER stress agonist)–induced apoptosis, such as the enhanced activity of caspase-3 and increase in GRP78 and CHOP expression. Moreover, treatment with 4-phenylbutyrate (4-PBA), an ER stress antagonist, significantly attenuated these HS-induced adverse effects in mGCs. In addition, boric acid supplementation in the culture medium significantly restored the decreased estradiol levels in heat-treated mGCs. The administration of boric acid to female mice previously exposed to hyperthermal conditions effectively restored the levels of serum estradiol in vivo. Collectively, these findings suggest that HS induces apoptosis in mGCs via ER stress pathways and that boron has a protective effect against these adverse effects. This study provides novel insights into the benefits of using boron against heat-induced apoptosis.

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Abbreviations

HS:

Heat stress

ER:

Endoplasmic reticulum

mGCs:

Mouse granulosa cells

GRP78:

Glucose-regulated protein 78

CHOP:

CCAAT/enhancer-binding protein (C/EBP) homologous protein

CYP19A1:

Cytochrome P450, family 19, subfamily A, member 1

HSP70:

Heat shock protein 70

PMSG:

Pregnant mare serum gonadotropin

4-PBA:

4-Phenylbutyrate

Tg:

Thapsigargin

E2 :

Estradiol

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Acknowledgments

We thank Editage (www.editage.cn) for the language editing services with English correction.

Funding

This study was funded by the start-up grants to scientific research of talents in Anhui Science and Technology University (No. DKYJ201801); Anhui Natural Science Foundation (No. 1908085QC145); National Natural Science Foundation of China (31702306); Natural Science Project of Education Department of Anhui (No. KJ2018ZD052); a support program for outstanding young talents of a university in Anhui (gxyqZD2019061); the foundation of first-class subject cultivation of veterinary science in Anhui Science and Technology University; and the University Natural Science Research Project of Anhui Province (KJ2015A288).

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  1. Yongjie Xiong and Erhui Jin contributed equally to this work.

Authors and Affiliations

  1. College of Animal Science, Anhui Science and Technology University, Fengyang, 233100, Anhui, China

    Yongjie Xiong, Erhui Jin, Qirun Yin, Chuanyan Che & Shaojun He

  2. Key Laboratory of the Quality and Safety Control for Pork of the Ministry of Agriculture, Anhui Science and Technology University, Fengyang, 233100, Anhui, China

    Yongjie Xiong, Erhui Jin, Qirun Yin, Chuanyan Che & Shaojun He

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  1. Yongjie Xiong
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Correspondence to Shaojun He.

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All the experimental procedures of this work were approved by the Committee for the Ethics on Animal Care and Experiments of College of Animal Science in Anhui Science and Technology University.

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Xiong, Y., Jin, E., Yin, Q. et al. Boron Attenuates Heat Stress–Induced Apoptosis by Inhibiting Endoplasmic Reticulum Stress in Mouse Granulosa Cells. Biol Trace Elem Res 199, 611–621 (2021). https://doi.org/10.1007/s12011-020-02180-1

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