Mitigating bisphenol A-induced apoptosis in KGN cells: the therapeutic role of 1,25-dihydroxyvitamin D3 through upregulation of PGC-1α expression and inhibition of the mitochondrial cytochrome c pathway

Liting Tang; Ke Du; Kaiming Luo; Long Wang; Fei Hua

doi:10.1007/s42000-024-00539-w

Mitigating bisphenol A-induced apoptosis in KGN cells: the therapeutic role of 1,25-dihydroxyvitamin D₃ through upregulation of PGC-1α expression and inhibition of the mitochondrial cytochrome c pathway

Hormones (Athens). 2024 Feb 29. doi: 10.1007/s42000-024-00539-w. Online ahead of print.

Authors

Liting Tang¹, Ke Du¹, Kaiming Luo¹, Long Wang¹, Fei Hua²

Affiliations

¹ Department of Endocrinology and Metabolism, The First People's Hospital of Changzhou, The Third Affiliated Hospital of Soochow University, Changzhou, 213003, China.
² Department of Endocrinology and Metabolism, The First People's Hospital of Changzhou, The Third Affiliated Hospital of Soochow University, Changzhou, 213003, China. huafei1970@suda.edu.cn.

PMID: 38421590
DOI: 10.1007/s42000-024-00539-w

Abstract

Purpose: This study investigated the potential of 1,25-dihydroxyvitamin D₃ (1,25(OH)₂VD₃) to mitigate bisphenol A (BPA)-induced apoptosis in human ovarian granulosa KGN cells with the aim of establishing a theoretical foundation for understanding of how vitamin D improved ovarian function in patients with polycystic ovary syndrome (PCOS).

Methods: The impact of varying concentrations of BPA and 1,25(OH)₂VD₃ on KGN cell viability was elucidated. It was established that BPA-induced apoptosis in KGN cells. Subsequently, KGN cells underwent pretreatment with 1,25(OH)₂VD₃, followed by exposure to BPA. The apoptosis rate, reactive oxygen species (ROS) levels, and mitochondrial function of the cells were meticulously assessed, along with the expression levels of genes associated with apoptosis as well as antioxidant and mitochondrial biogenesis.

Results: BPA induced a notable increase in apoptosis (P < 0.001) and oxidative stress (P < 0.001) in KGN cells, accompanied by a significant reduction in mitochondrial membrane potential (P < 0.001) and severe impairment of mitochondrial function. Following pretreatment of KGN cells with 1,25(OH)₂VD₃, there was a significant decrease in the apoptosis rate (P = 0.004), coupled with a reduction in ROS production (P = 0.002). Concomitantly, the upregulation of PGC-1α (P = 0.009) and SOD (P = 0.018) was observed, while mRNA expression of BAX (P = 0.011), Cyt c (P = 0.001), Apaf-1 (P = 0.012), caspase-9 (P < 0.001), and caspase-3 (P = 0.011) was downregulated. Notably, the mitigation of mitochondrial damage was evident through restored mitochondrial membrane potential (P < 0.001), as corroborated by electron microscope results.

Conclusions: 1,25(OH)₂VD₃ mitigated BPA-induced damage and apoptosis in KGN cells by upregulating the expression of PGC-1α and impeding the mitochondrial cytochrome c (Cyt c) apoptotic pathway. This study established a novel theoretical foundation for utilizing vitamin D in the treatment of PCOS patients.

Keywords: 1,25-dihydroxyvitamin D3; Apoptosis; Bisphenol A; KGN cells; Polycystic ovary syndrome.

Abstract

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