2. Academic Validation
  3. Bisphenol a downregulates GLUT4 expression by activating aryl hydrocarbon receptor to exacerbate polycystic ovary syndrome

Bisphenol a downregulates GLUT4 expression by activating aryl hydrocarbon receptor to exacerbate polycystic ovary syndrome

  • Cell Commun Signal. 2024 Jan 10;22(1):28. doi: 10.1186/s12964-023-01410-y.
Jing Shi 1,  Kai-Lun Hu 2 3 4 5,  Xiao-Xue Li 2 3,  Yi-Meng Ge 2 3,  Xiao-Jun Yu 6,  Jie Zhao 7 8 9 10
Affiliations

Affiliations

  • 1 Department of Pharmacy, Peking University Third Hospital, Beijing, China.
  • 2 Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, 49 North Garden Rd, Haidian District, Beijing, 100191, China.
  • 3 National Clinical Research Center for Obstetrics and Gynecology, Beijing, 100191, China.
  • 4 Key Laboratory of Assisted Reproduction (Peking University), Ministry of Education, Beijing, 100191, China.
  • 5 Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology, Beijing, 100191, China.
  • 6 Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming, China.
  • 7 Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, 49 North Garden Rd, Haidian District, Beijing, 100191, China. 2358044941@qq.com.
  • 8 National Clinical Research Center for Obstetrics and Gynecology, Beijing, 100191, China. 2358044941@qq.com.
  • 9 Key Laboratory of Assisted Reproduction (Peking University), Ministry of Education, Beijing, 100191, China. 2358044941@qq.com.
  • 10 Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology, Beijing, 100191, China. 2358044941@qq.com.
PMID: 38200540 DOI: 10.1186/s12964-023-01410-y
Abstract

Background: Bisphenol A (BPA) levels are high in women with polycystic ovary syndrome (PCOS). The mechanism by which BPA induces abnormal glucose metabolism in PCOS patients is largely unknown.

Methods: Serum and urine samples were collected from women with and without PCOS (control) at the reproductive medicine center with informed consent. Non-PCOS patients who received in vitro fertilization were recruited for collection of ovarian follicular fluid and granular cells. Wild-type C57BL/6 and AhR -/- mice were used to verify the effects of BPA on PCOS. Real-Time PCR, western blotting, and ELISA were conducted to analyze the function of BPA. Chip-qPCR verified the role of AhR in GLUT4 transcription. Flow cytometry was performed to determine glucose uptake.

Results: A positive correlation was observed between BPA concentration and serum BPA levels in PCOS patients. BPA aggravated the changes in PCOS with abnormal glucose metabolism, impaired fertility, and increased body fat. Mechanistically, we showed that BPA activated AhR and led to decreased glucose transport via GLUT4 downregulation in ovarian granular cells. Therefore, the use of inhibitors or knockout of AhR could effectively rescue BPA-induced metabolic disorders in PCOS mice.

Conclusions: Our results revealed that BPA suppressed GLUT4 expression and induced abnormal glucose metabolism by activating AhR, causing Insulin resistance, and is thus a potential contributor to the development of PCOS. Therefore, AhR could be a potential new therapeutic target for PCOS. Video Abstract.

Keywords

Aryl hydrocarbon receptor; Bisphenol a; Glucose transporter 4; Ovarian granulosa cells; Polycystic ovary syndrome.

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