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  3. Copper mediated follicular atresia: Implications for granulosa cell death

Copper mediated follicular atresia: Implications for granulosa cell death

  • J Hazard Mater. 2024 Sep 15:477:135391. doi: 10.1016/j.jhazmat.2024.135391.
Shuang Wu 1,  Mailin Gan 1,  Yan Wang 1,  Yuheng Pan 1,  Yuxu He 1,  Jinkang Feng 1,  Ye Zhao 1,  Lili Niu 1,  Lei Chen 1,  Shunhua Zhang 1,  Li Zhu 2,  Linyuan Shen 3
Affiliations

Affiliations

  • 1 Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, China; Key Laboratory of Livestock and Poultry Multi-omics, Ministry of Agriculture and Rural Affairs, College of Animal and Technology, Sichuan Agricultural University, Chengdu 611130, China; State Key Laboratory of Swine and Poultry Breeding Industry, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, China.
  • 2 Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, China; Key Laboratory of Livestock and Poultry Multi-omics, Ministry of Agriculture and Rural Affairs, College of Animal and Technology, Sichuan Agricultural University, Chengdu 611130, China; State Key Laboratory of Swine and Poultry Breeding Industry, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, China. Electronic address: zhuli@sicau.edu.cn.
  • 3 Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, China; Key Laboratory of Livestock and Poultry Multi-omics, Ministry of Agriculture and Rural Affairs, College of Animal and Technology, Sichuan Agricultural University, Chengdu 611130, China; State Key Laboratory of Swine and Poultry Breeding Industry, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, China. Electronic address: shenlinyuan@sicau.edu.cn.
PMID: 39106724 DOI: 10.1016/j.jhazmat.2024.135391
Abstract

3-nitropropanoic acid is a potent oxidative stress inducer that is conventionally regarded as a regulator of follicular atresia by regulating granulosa cells (GCs) death through the Apoptosis pathway. There has been no research investigating the impact of copper metal overload induced Cuproptosis in ovarian GCs as a factor contributing to hindered follicular development.To elucidate whether 3-NP-induced oxidative stress plays a contributory role in promoting Cuproptosis, and discuss the role of Cuproptosis in the development of ovarian follicles.We conducted an analysis of Cuproptosis occurrence in murine GCs and C57BL/6 J mice under the influence of 3-NP and 3-NP with added exogenous copper.The results revealed that 3-NP serving as a robust facilitator of exogenous copper uptake by upregulating the expression of copper transporter 1 (CTR1). In turn, culminated in the accumulation of intracellular copper within mouse granulosa cells (mGCs). Furthermore, 3-NP promoted mitochondrial permeability transition pore opening and concurrently reduced the stability of lipoic acid proteins. These actions collectively induced the oligomerization of Dihydrolipoamide S-Acetyltransferase (DLAT), ultimately leading to Cuproptosis in GCs and consequent follicular atresia. Heavy metal copper and Fungal decomposition product 3-NP, induce ovarian atresia via Cuproptosis, modulating the reproductive performance of female Animals.

Keywords

3-NP; Copper; Cuproptosis; Follicular atresia; Granulosa cells.

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