Distinct metabolic signatures in blood plasma of bisphenol A–exposed women with polycystic ovarian syndrome

Abstract

Polycystic ovarian syndrome (PCOS) is a complicated endocrinopathy with an unclear etiology that afflicts fertility status in women. Although the underlying causes and pathophysiology of PCOS are not completely understood, it is suspected to be driven by environmental factors as well as genetic and epigenetic factors. Bisphenol A (BPA) is a weak estrogenic endocrine disruptor known to cause adverse reproductive outcomes in women. A growing relevance supports the notion that BPA may contribute to PCOS pathogenesis. Due to the indeterminate molecular mechanisms of BPA in PCOS endocrinopathy, we sought liquid chromatography with tandem mass spectrometry (LC–MS/MS), a metabolomics strategy that could generate a metabolic signature based on urinary BPA levels of PCOS and healthy individuals. Towards this, we examined urinary BPA levels in PCOS and healthy women by ELISA and performed univariate and chemometric analysis to distinguish metabolic patterns among high and low BPA in PCOS and healthy females, followed by pathway and biomarker analysis employing MetaboAnalyst 5.0. Our findings indicated aberrant levels of certain steroids, sphingolipids, and others, implying considerable disturbances in steroid hormone biosynthesis, linoleic, linolenic, sphingolipid metabolism, and various other pathways across target groups in comparison to healthy women with low BPA levels. Collectively, our findings provide insight into metabolic signatures of BPA-exposed PCOS women, which can potentially improve management strategies and precision medicine.

Role of polyphenols in remodeling the host gut microbiota in polycystic ovary syndrome

“…BPA has weak estrogenic effects and can increase the secretion of ovarian androgens in most animals [ 24 ]. After BPA accumulation has occurred in the body of patients with PCOS, it has also been found to delay and reduce the clearance of excess androgens in the body, thereby aggravating metabolic dysfunction and increasing the risk of PCOS [ 25 ]. Hyperandrogenemia is an essential endocrine feature of PCOS, and the androgen-excessive environment can inhibit follicle development and maturation, resulting in follicular atresia and decreased ovarian estradiol levels [ 26 ].…”

Advances in understanding the reproductive toxicity of endocrine-disrupting chemicals in women

“…In women undergoing assisted reproductive treatment, a significant correlation has been observed between elevated urinary BPA levels and reduced antral follicle count, decreased oocyte quantity, lower fertilization rates, and implantation failures (Pivonello et al, 2020). Furthermore, PCOS women exhibit significantly higher total serum BPA exposure compared to the control group (PCOS: 167.04 ± 9.44 IU/mL, control: 31.94 ± 3.57 IU/mL), suggesting that higher BPA level in the follicular fluid of PCOS patients (PCOS: 440.50 ± 63.70 pg/mL, control: 338.00 ± 57.88 pg/mL) may play a crucial role in its pathogenesis by reducing aromatase expression in granulosa cells (Wang et al, 2017;Prabhu et al, 2023). Epidemiological meta-analyses have found an association between endometriosis development and BPA exposure due to its influence on epigenetics (Xue et al, 2021).…”

Invisible Hand behind Female Reproductive Disorders: Bisphenols, Recent Evidence and Future Perspectives

“…This relationship suggests that BPA inhibits the synthesis of ovarian steroids [ 274 ]. Compared with healthy women with low internal BPA levels, women with PCOS exhibit abnormal levels of certain steroids and phospholipids, indicating impaired activity of pathways associated with steroid hormone biosynthesis, arachidonic acid metabolism, linoleic acid metabolism, and phospholipid metabolism [ 275 ]. In addition to affecting the production of steroid hormones, BPA affects the quantity of ovarian follicles and diminishes ovarian reserve in patients with PCOS [ 276 ].…”