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

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.

Bisphenol A exposure modulates reproductive and endocrine system, mitochondrial function and cellular senescence in female adult rats: A hallmarks of polycystic ovarian syndrome phenotype.

Bisphenol A (BPA) mimics estrogen and consequently suspected to be detrimental to female reproductive system. Biomonitoring confirms the BPA burden in body leading to a complex condition called polycystic ovarian syndrome (PCOS) which is frequently attributed to female infertility. Due to unclear precise molecular pathomechanisms of BPA in PCOS, we intend to examine the molecular mechanisms of the reproductive, endocrine, mitochondrial features, and cellular senescence in BPA-treated rats. We analyzed vaginal smears and ovarian follicles using microscope, assessed sex hormones by ELISA, analyzed BPA target gene expression by semi-quantitative RT-PCR, assessed senescence induction by ß-galactosidase staining and immunofluorescence in BPA-treated rats. Our data showed hormonal imbalance, impaired folliculogenesis, abnormal expression patterns of target genes, CDKN2A overexpression and enhanced ROS levels in BPA-treated rats. This study provides insights on the effects of BPA exposure on ovulatory, hormonal, mitochondrial dysfunction, and senescence that benefit in better understanding of PCOS induced by BPA.

Pharmacogenomics deliberations of 2-deoxy-d-glucose in the treatment of COVID-19 disease: an in silico approach.

The outbreak of COVID-19 caused by the coronavirus (SARS-CoV-2) prompted number of computational and laboratory efforts to discover molecules against the virus entry or replication. Simultaneously, due to the availability of clinical information, drug-repurposing efforts led to the discovery of 2-deoxy-d-glucose (2-DG) for treating COVID-19 infection. 2-DG critically accumulates in the infected cells to prevent energy production and viral replication. As there is no clarity on the impact of genetic variations on the efficacy and adverse effects of 2-DG in treating COVID-19 using in silico approaches, we attempted to extract the genes associated with the 2-DG pathway using the Comparative Toxicogenomics Database. The interaction between selected genes was assessed using ClueGO, to identify the susceptible gene loci for SARS-CoV infections. Further, SNPs that were residing in the distinct genomic regions were retrieved from the Ensembl genome browser and characterized. A total of 80 SNPs were retrieved using diverse bioinformatics resources after assessing their (a) detrimental influence on the protein stability using Swiss-model, (b) miRNA regulation employing miRNASNP3, PolymiRTS, MirSNP databases, (c) binding of transcription factors by SNP2TFBS, SNPInspector, and (d) enhancers regulation using EnhancerDB and HaploReg reported A2M rs201769751, PARP1 rs193238922 destabilizes protein, six polymorphisms of XIAP effecting microRNA binding sites, EGFR rs712829 generates 15 TFBS, BECN1 rs60221525, CASP9 rs4645980, SLC2A2 rs5393 impairs 14 TFBS, STK11 rs3795063 altered 19 regulatory motifs. These data may provide the relationship between genetic variations and drug effects of 2-DG which may further assist in assigning the right individuals to benefit from the treatment. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-022-03363-4.

Review on bisphenol A and the risk of polycystic ovarian syndrome: an insight from endocrine and gene expression.

Bisphenol A (BPA) is one of the most widely studied endocrine disrupting chemicals because of its structural similarity to 17-ß estradiol; its ability to bind as an agonist/antagonist to estrogen receptors elicits adverse effects on the functioning of the metabolic and endocrinal system. Therefore, BPA has been thoroughly scrutinized concerning its disruption of pathways like lipid metabolism, steroidogenesis, insulin signaling, and inflammation. This has resulted in reports of its correlation with various aspects of cardiovascular diseases, obesity, diabetes, male and female reproductive disorders, and dysfunctions. Among these, the occurrence of the polycystic ovarian syndrome (PCOS) in premenopausal women is of great concern. PCOS is a highly prevalent disorder affecting women in their reproductive age and is clinically characterized by hyperandrogenism, ovulatory dysfunction, and polycystic ovarian morphology, along with metabolism-related dysfunctions like hyperinsulinemia, obesity, and insulin resistance. In this review, we analyzed certain researched effects of BPA, while focusing on its ability to alter the expression of various significant genes like GnRH, AdipoQ, ESR1, StAR, CYP11A1, CYP19A1, and many more involved in the pathways and endocrine regulation, whose disruption is commonly associated with the clinical manifestations of PCOS.