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ORIGINAL RESEARCH article

Front. Endocrinol.
Sec. Reproduction
Volume 16 - 2025 | doi: 10.3389/fendo.2025.1514105

Bisphenol A attenuates testosterone synthesis via increasing Apolipoprotein A1-mediated reverse cholesterol transport in mice

Provisionally accepted
Lijia Zhao Lijia Zhao *Tong Zhao Tong Zhao Wenzhe Yang Wenzhe Yang Feilong Pan Feilong Pan Jinhao Wang Jinhao Wang Wenqi Shao Wenqi Shao Fangfang Chen Fangfang Chen Kexiang Liu Kexiang Liu Shuchen Zhao Shuchen Zhao
  • College of Veterinary Medicine, Northeast Agricultural University, Harbin, China

The final, formatted version of the article will be published soon.

    Bisphenol A (BPA), a widely used chemical compound in plastic manufacturing, has become ubiquitous in the environment. Previous studies have highlighted its adverse effects on reproductive function, as BPA exposure reduces testosterone levels. Cholesterol is involved in testosterone synthesis in Leydig cells. However, research on the mechanisms by which BPA affects testosterone synthesis from the perspective of reverse cholesterol transport (RCT) remains limited. This study aimed to investigate the effects of BPA on cholesterol levels, lipid droplet accumulation, and testosterone synthesis in TM3 cells and mice via Apolipoprotein A1 (APOA1)-mediated RCT. It was observed that serum and testicular testosterone levels were drastically reduced in BPA-treated mice. Moreover, lipid droplets accumulation and testicular total (TC) and free cholesterol (FC) levels were reduced in the mouse testes. Conversely, testicular high-density lipoprotein (HDL) content was partially elevated. Furthermore, BPA markedly enhanced Apoa1 mRNA and protein expression in the mouse model. Notably, BPA significantly upregulated Apoa1 mRNA and protein level, reduced cholesterol levels and lipid droplets accumulation, and attenuated testosterone synthesis in TM3 cells. In addition, exogenous supplement with 22-hydoxycholesterol promoted testosterone synthesis and alleviated the inhibitory effect of BPA on testosterone synthesis. Taken together, these results suggest that BPA upregulates APOA1 expression, enhances RCT, and ultimately reduces TC and FC levels in the testis. This cholesterol reduction likely led to testosterone synthesis disorders in the model, indicating that BPA inhibits testosterone synthesis in mice by disrupting cholesterol transport.

    Keywords: bisphenol A, apolipoprotein A1, Cholesterol, reverse cholesterol transport, Testosterone, lipid droplet

    Received: 20 Oct 2024; Accepted: 09 Jan 2025.

    Copyright: © 2025 Zhao, Zhao, Yang, Pan, Wang, Shao, Chen, Liu and Zhao. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Lijia Zhao, College of Veterinary Medicine, Northeast Agricultural University, Harbin, China

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