Bisphenol A attenuates testosterone synthesis via increasing apolipoprotein A1-mediated reverse cholesterol transport in mice
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 Ley...
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Frontiers Media S.A.
2025-01-01
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| Series: | Frontiers in Endocrinology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fendo.2025.1514105/full |
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| author | 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 Lijia Zhao Lijia Zhao |
| author_facet | 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 Lijia Zhao Lijia Zhao |
| author_sort | Tong Zhao |
| collection | DOAJ |
| description | 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. Adult male mice were treated by intraperitoneal injection of corn oil containing BPA (20 mg/kg) for 7 days. Testes were collected for protein extraction, RNA extraction, Oil red O staining or for Biochemical analysis. Serums were collected for detection of testosterone levels. flow cytometry, CCK8 assay, immunofluorescence or Filipin III staining was used to detect the effect of BPA on the TM3 cells. 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. |
| format | Article |
| id | doaj-art-99d1d6e78f904bafa9d037172f8238c6 |
| institution | Kabale University |
| issn | 1664-2392 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Endocrinology |
| spelling | doaj-art-99d1d6e78f904bafa9d037172f8238c62025-01-28T05:10:37ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922025-01-011610.3389/fendo.2025.15141051514105Bisphenol A attenuates testosterone synthesis via increasing apolipoprotein A1-mediated reverse cholesterol transport in miceTong Zhao0Tong Zhao1Wenzhe Yang2Wenzhe Yang3Feilong Pan4Feilong Pan5Jinhao Wang6Jinhao Wang7Wenqi Shao8Wenqi Shao9Fangfang Chen10Fangfang Chen11Kexiang Liu12Kexiang Liu13Shuchen Zhao14Shuchen Zhao15Lijia Zhao16Lijia Zhao17College of Veterinary Medicine, Northeast Agricultural University, Harbin, Heilongjiang, ChinaKey Laboratory of the Provincial Education Department of Heilongjiang for Common Animal Disease Prevention and Treatment, Harbin, Heilongjiang, ChinaCollege of Veterinary Medicine, Northeast Agricultural University, Harbin, Heilongjiang, ChinaKey Laboratory of the Provincial Education Department of Heilongjiang for Common Animal Disease Prevention and Treatment, Harbin, Heilongjiang, ChinaCollege of Veterinary Medicine, Northeast Agricultural University, Harbin, Heilongjiang, ChinaKey Laboratory of the Provincial Education Department of Heilongjiang for Common Animal Disease Prevention and Treatment, Harbin, Heilongjiang, ChinaCollege of Veterinary Medicine, Northeast Agricultural University, Harbin, Heilongjiang, ChinaKey Laboratory of the Provincial Education Department of Heilongjiang for Common Animal Disease Prevention and Treatment, Harbin, Heilongjiang, ChinaCollege of Veterinary Medicine, Northeast Agricultural University, Harbin, Heilongjiang, ChinaKey Laboratory of the Provincial Education Department of Heilongjiang for Common Animal Disease Prevention and Treatment, Harbin, Heilongjiang, ChinaCollege of Veterinary Medicine, Northeast Agricultural University, Harbin, Heilongjiang, ChinaKey Laboratory of the Provincial Education Department of Heilongjiang for Common Animal Disease Prevention and Treatment, Harbin, Heilongjiang, ChinaCollege of Veterinary Medicine, Northeast Agricultural University, Harbin, Heilongjiang, ChinaKey Laboratory of the Provincial Education Department of Heilongjiang for Common Animal Disease Prevention and Treatment, Harbin, Heilongjiang, ChinaCollege of Veterinary Medicine, Northeast Agricultural University, Harbin, Heilongjiang, ChinaKey Laboratory of the Provincial Education Department of Heilongjiang for Common Animal Disease Prevention and Treatment, Harbin, Heilongjiang, ChinaCollege of Veterinary Medicine, Northeast Agricultural University, Harbin, Heilongjiang, ChinaKey Laboratory of the Provincial Education Department of Heilongjiang for Common Animal Disease Prevention and Treatment, Harbin, Heilongjiang, ChinaBisphenol 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. Adult male mice were treated by intraperitoneal injection of corn oil containing BPA (20 mg/kg) for 7 days. Testes were collected for protein extraction, RNA extraction, Oil red O staining or for Biochemical analysis. Serums were collected for detection of testosterone levels. flow cytometry, CCK8 assay, immunofluorescence or Filipin III staining was used to detect the effect of BPA on the TM3 cells. 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.https://www.frontiersin.org/articles/10.3389/fendo.2025.1514105/fullbisphenol Aapolipoprotein A1cholesterolreverse cholesterol transporttestosteronelipid droplet |
| spellingShingle | 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 Lijia Zhao Lijia Zhao Bisphenol A attenuates testosterone synthesis via increasing apolipoprotein A1-mediated reverse cholesterol transport in mice Frontiers in Endocrinology bisphenol A apolipoprotein A1 cholesterol reverse cholesterol transport testosterone lipid droplet |
| title | Bisphenol A attenuates testosterone synthesis via increasing apolipoprotein A1-mediated reverse cholesterol transport in mice |
| title_full | Bisphenol A attenuates testosterone synthesis via increasing apolipoprotein A1-mediated reverse cholesterol transport in mice |
| title_fullStr | Bisphenol A attenuates testosterone synthesis via increasing apolipoprotein A1-mediated reverse cholesterol transport in mice |
| title_full_unstemmed | Bisphenol A attenuates testosterone synthesis via increasing apolipoprotein A1-mediated reverse cholesterol transport in mice |
| title_short | Bisphenol A attenuates testosterone synthesis via increasing apolipoprotein A1-mediated reverse cholesterol transport in mice |
| title_sort | bisphenol a attenuates testosterone synthesis via increasing apolipoprotein a1 mediated reverse cholesterol transport in mice |
| topic | bisphenol A apolipoprotein A1 cholesterol reverse cholesterol transport testosterone lipid droplet |
| url | https://www.frontiersin.org/articles/10.3389/fendo.2025.1514105/full |
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