The Effect of Bisphenol A on the Pathogenesis of Polycystic Ovary Syndrome

doi:10.12280/gjfckx.20230260

Abstract

Abstract:

Polycystic ovary syndrome (PCOS) is a common endocrine disease characterized by hyperandrogenic phenotype in women of reproductive age. The pathogenesis of PCOS remains unclear, and androgen is now thought to have an essential impact on the pathogenesis of PCOS. Bisphenol A (BPA), an environmental endocrine disruptor, can increase the relevant androgen synthetase and induce PCOS through excessive androgen exposure. Studies have shown that BPA exposure can inhibit the activity of aromatase, prevent the binding of androgen and receptor, thus inducing hyperandrogenemia. BPA can also regulate the ovarian function of PCOS through oxidative stress, estrogen-related pathways, hypothalamic-pituitary-ovarian axis, regulation of obesity and insulin resistance, and other routes. This article aims to review the neuroendocrine mechanism and related signal pathways of BPA-induced PCOS by regulating hyperandrogen, clarify the specific biological functions of BPA and provide a reference for follow-up research.

Key words: Bisphenol A, Receptors, estrogen, Polycystic ovary syndrome, Endocrine system, Receptors, androgen

SUN Yi-wen, XIONG Ke, ZHANG Zi-xu, WENG Ya-jing, WANG Yong. The Effect of Bisphenol A on the Pathogenesis of Polycystic Ovary Syndrome[J]. Journal of International Obstetrics and Gynecology, 2023, 50(6): 601-605.

References 33

[1]	潘雷, 徐键. 多囊卵巢综合征患者雄激素代谢异常的研究进展[J]. 中外医学研究, 2021, 19(12):192-196. doi: 10.14033/j.cnki.cfmr.2021.12.069.
[2]	Escobar-Morreale HF. Polycystic ovary syndrome: definition, aetiology, diagnosis and treatment[J]. Nat Rev Endocrinol, 2018, 14(5):270-284. doi: 10.1038/nrendo.2018.24. pmid: 29569621
[3]	Aflatounian A, Edwards MC, Rodriguez Paris V, et al. Androgen signaling pathways driving reproductive and metabolic phenotypes in a PCOS mouse model[J]. J Endocrinol, 2020, 245(3):381-395. doi: 10.1530/JOE-19-0530. pmid: 32229702
[4]	Persson S, Ubhayasekera KA, Bergquist J, et al. Hyperandrogenic Symptoms Are a Persistent Suffering in Midlife Women with PCOS; a Prospective Cohort Study in Sweden[J]. Biomedicines, 2022, 11(1):96. doi: 10.3390/biomedicines11010096.
[5]	乔杰, 齐新宇, 徐雅兰, 等. 关注影响女性健康的重要生殖内分泌疾病多囊卵巢综合征[J]. 中国实用妇科与产科杂志, 2020, 36(1):1-9. doi: 10.19538/j.fk2020010101.
[6]	Nordenström A, Falhammar H. MANAGEMENT OF ENDOCRINE DISEASE: Diagnosis and management of the patient with non-classic CAH due to 21-hydroxylase deficiency[J]. Eur J Endocrinol, 2019, 180(3):R127-R145. doi: 10.1530/EJE-18-0712.
[7]	Liao B, Qi X, Yun C, et al. Effects of Androgen Excess-Related Metabolic Disturbances on Granulosa Cell Function and Follicular Development[J]. Front Endocrinol(Lausanne), 2022, 13:815968. doi: 10.3389/fendo.2022.815968.
[8]	Zhang Y, Zhao W, Xu H, et al. Hyperandrogenism and insulin resistance-induced fetal loss: evidence for placental mitochondrial abnormalities and elevated reactive oxygen species production in pregnant rats that mimic the clinical features of polycystic ovary syndrome[J]. J Physiol, 2019, 597(15):3927-3950. doi: 10.1113/JP277879.
[9]	Kechagias KS, Semertzidou A, Athanasiou A, et al. Bisphenol-A and polycystic ovary syndrome: a review of the literature[J]. Rev Environ Health, 2020, 35(4):323-331. doi: 10.1515/reveh-2020-0032.
[10]	Merii MH, Fardoun MM, El Asmar K, et al. Effect of BPA on CYP450s expression, and nicotine modulation, in fetal rat brain[J]. Neurotoxicol Teratol, 2022, 92:107095. doi: 10.1016/j.ntt.2022.107095.
[11]	Shen J, Kang Q, Mao Y, et al. Urinary bisphenol A concentration is correlated with poorer oocyte retrieval and embryo implantation outcomes in patients with tubal factor infertility undergoing in vitro fertilisation[J]. Ecotoxicol Environ Saf, 2020, 187:109816. doi: 10.1016/j.ecoenv.2019.109816.
[12]	Segovia-Mendoza M, Gómez de León CT, García-Becerra R, et al. The chemical environmental pollutants BPA and BPS induce alterations of the proteomic profile of different phenotypes of human breast cancer cells: A proposed interactome[J]. Environ Res, 2020, 191:109960. doi: 10.1016/j.envres.2020.109960.
[13]	Ni Y, Hu L, Yang S, et al. Bisphenol A impairs cognitive function and 5-HT metabolism in adult male mice by modulating the microbiota-gut-brain axis[J]. Chemosphere, 2021, 282:130952. doi: 10.1016/j.chemosphere.2021.130952.
[14]	Welch C, Mulligan K. Does Bisphenol A Confer Risk of Neurodevelopmental Disorders? What We Have Learned from Developmental Neurotoxicity Studies in Animal Models[J]. Int J Mol Sci, 2022, 23(5):2894. doi: 10.3390/ijms23052894.
[15]	Sharif K, Kurnick A, Coplan L, et al. The Putative Adverse Effects of Bisphenol A on Autoimmune Diseases[J]. Endocr Metab Immune Disord Drug Targets, 2022, 22(7):665-676. doi: 10.2174/1871530321666210210154309.
[16]	Della Rocca Y, Traini EM, Diomede F, et al. Current Evidence on Bisphenol A Exposure and the Molecular Mechanism Involved in Related Pathological Conditions[J]. Pharmaceutics, 2023, 15(3):908. doi: 10.3390/pharmaceutics15030908.
[17]	Šimková M, Vítků J, Kolátorová L, et al. Endocrine disruptors, obesity, and cytokines-how relevant are they to PCOS?[J]. Physiol Res, 2020, 69(Suppl 2):S279-S293. doi: 10.33549/physiolres.934521. pmid: 33094626
[18]	Kawa IA, Masood A, Fatima Q, et al. Bisphenol A (BPA) act as an endocrine disruptor in women with Polycystic Ovary Syndrome: Hormonal and metabolic evaluation[J]. Obesity Medicine, 2019, 14:100090. doi: 10.1016/j.obmed.2019.100090.
[19]	Konieczna A, Rachoń D, Owczarek K, et al. Serum bisphenol A concentrations correlate with serum testosterone levels in women with polycystic ovary syndrome[J]. Reprod Toxicol, 2018, 82:32-37. doi: 10.1016/j.reprotox.2018.09.006. pmid: 30266220
[20]	Wang K, Huang D, Zhou P, et al. BPA-induced prostatic hyperplasia in vitro is correlated with the unbalanced gene expression of AR and ER in the epithelium and stroma[J]. Toxicol Ind Health, 2021, 37(10):585-593. doi: 10.1177/07482337211042986.
[21]	Lim SC, Geleta B, Maleki S, et al. The metastasis suppressor NDRG1 directly regulates androgen receptor signaling in prostate cancer[J]. J Biol Chem, 2021, 297(6):101414. doi: 10.1016/j.jbc.2021.101414.
[22]	Huang X, Cang X, Liu J. Molecular mechanism of Bisphenol A on androgen receptor antagonism[J]. Toxicol In Vitro, 2019, 61:104621. doi: 10.1016/j.tiv.2019.104621.
[23]	MacKay H, Abizaid A. A plurality of molecular targets: The receptor ecosystem for bisphenol-A (BPA)[J]. Horm Behav, 2018, 101:59-67. doi: 10.1016/j.yhbeh.2017.11.001. pmid: 29104009
[24]	Shi J, Liu C, Chen M, et al. The interference effects of bisphenol A on the synthesis of steroid hormones in human ovarian granulosa cells[J]. Environ Toxicol, 2021, 36(4):665-674. doi: 10.1002/tox.23070. pmid: 33258555
[25]	Eldefrawy F, Xu HS, Pusch E, et al. Modulation of folliculogenesis in adult laying chickens by bisphenol A and bisphenol S: Perspectives on ovarian morphology and gene expression[J]. Reprod Toxicol, 2021, 103:181-190. doi: 10.1016/j.reprotox.2021.06.010. pmid: 34147626
[26]	Wang D, Weng Y, Zhang Y, et al. Exposure to hyperandrogen drives ovarian dysfunction and fibrosis by activating the NLRP3 inflammasome in mice[J]. Sci Total Environ, 2020, 745:141049. doi: 10.1016/j.scitotenv.2020.141049.
[27]	Fan X, Hou T, Jia J, et al. Discrepant dose responses of bisphenol A on oxidative stress and DNA methylation in grass carp ovary cells[J]. Chemosphere, 2020, 248:126110. doi: 10.1016/j.chemosphere.2020.126110.
[28]	Roepke TA, Sadlier NC. REPRODUCTIVE TOXICOLOGY: Impact of endocrine disruptors on neurons expressing GnRH or kisspeptin and pituitary gonadotropins[J]. Reproduction, 2021, 162(5):F131-F145. doi: 10.1530/REP-20-0612. pmid: 34228631
[29]	陶亚楠, 毛亚萍, 杨俏俏, 等. 妊娠期双酚A暴露影响子代雌性大鼠卵巢功能与Wnt/β-catenin信号通路调控机制[J]. 中国职业医学, 2022, 49(1):34-40. doi: 10.20001/j.issn.2095-2619.2022006.
[30]	Ye Y, Tang Y, Xiong Y, et al. Bisphenol A exposure alters placentation and causes preeclampsia-like features in pregnant mice involved in reprogramming of DNA methylation of WNT2[J]. FASEB J, 2019, 33(2):2732-2742. doi: 10.1096/fj.201800934RRR. pmid: 30303745
[31]	Cimmino I, Fiory F, Perruolo G, et al. Potential Mechanisms of Bisphenol A (BPA) Contributing to Human Disease[J]. Int J Mol Sci, 2020, 21(16):5761. doi: 10.3390/ijms21165761.
[32]	Wade M, Delawder V, Reneau P, et al. The effect of BPA exposure on insulin resistance and type 2 diabetes - The impact of muscle contraction[J]. Med Hypotheses, 2020, 140:109675. doi: 10.1016/j.mehy.2020.109675.
[33]	Hong SH, Sung YA, Hong YS, et al. Urinary bisphenol A is associated with insulin resistance and obesity in reproductive-aged women[J]. Clin Endocrinol (Oxf), 2017, 86(4):506-512. doi: 10.1111/cen.13270.