Impact of Environmentally Relevant Concentrations of Bisphenol A (BPA) on the Gene Expression Profile in an In Vitro Model of the Normal Human Ovary

Abstract

Endocrine-disrupting chemicals (EDCs), including the xenoestrogen Bisphenol A (BPA), can interfere with hormonal signalling. Despite increasing reports of adverse health effects associated with exposure to EDCs, there are limited data on the effect of BPA in normal human ovaries. In this paper, we present a detailed analysis of the transcriptomic landscape in normal Human Epithelial Ovarian Cells (HOSEpiC) treated with BPA (10 and 100 nM). Gene expression profiles were determined using high-throughput RNA sequencing, followed by functional analyses using bioinformatics tools. In total, 272 and 454 differentially expressed genes (DEGs) were identified in 10 and 100 nM BPA-treated HOSEpiCs, respectively, compared to untreated controls. Biological pathways included mRNA surveillance pathways, oocyte meiosis, cellular senescence, and transcriptional misregulation in cancer. BPA exposure has a considerable impact on 10 genes: ANAPC2, AURKA, CDK1, CCNA2, CCNB1, PLK1, BUB1, KIF22, PDE3B, and CCNB3, which are also associated with progesterone-mediated oocyte maturation pathways. Future studies should further explore the effects of BPA and its metabolites in the ovaries in health and disease, making use of validated in vitro and in vivo models to generate data that will address existing knowledge gaps in basic biology, hazard characterisation, and risk assessment associated with the use of xenoestrogens such as BPA.

Hybrid CTAB–Silica and APTES-Functionalized Multi-Walled Carbon Nanotubes for Adsorption-Enhanced Electrochemical Detection of Bisphenol A in Environmental and Food Samples

“…The use of concentrated PBS promotes desorption of residual BPA and weakly adsorbed species, allowing partial recovery of the electrode surface. 84,85 As shown in Figs. 8a, 8b, the current response remained relatively stable over the five cycles, with a slight decrease observed after the first measurement, resulting in an RSD of 1.30%.…”

Hybrid CTAB–Silica and APTES-Functionalized Multi-Walled Carbon Nanotubes for Adsorption-Enhanced Electrochemical Detection of Bisphenol A in Environmental and Food Samples

“…The use of concentrated PBS promotes desorption of residual BPA and weakly adsorbed species, allowing partial recovery of the electrode surface. 84,85 As shown in Figs. 8a, 8b, the current response remained relatively stable over the five cycles, with a slight decrease observed after the first measurement, resulting in an RSD of 1.30%.…”

Differential Regulation of Genes by the Glucogenic Hormone Asprosin in Ovarian Cancer

“…Following treatment with 100 nM of asprosin, the serous OvCa cell line, SKOV-3, displayed 160 and 173 gene changes, at 4 and 12 h, respectively, when compared with control samples extracted at parallel time points, p < 0.05 and Log2FC > 1. DEGs were identified using the Cuffdiff multiple-testing module [ 28 ]. These changes are mapped in the volcano plots presented in Figure 1 .…”

Bisphenol A and ovarian cancer: emerging evidence and potential biological mechanisms

“…RNA sequencing of normal human ovarian cells exposed to BPA identified differentially expressed genes that were enriched in pathways related to mRNA surveillance, cellular senescence, and transcriptional regulation. These enrichment results suggest candidate biological processes affected by BPA but do not demonstrate direct activation of these pathways or establish their causal involvement in ovarian carcinogenesis ( Zahra et al, 2022 ). Notably, a subset of these BPA-responsive genes overlaps with those regulated by 17β-estradiol (E2), particularly in pathways associated with cell proliferation and migration, suggesting that BPA partially recapitulates estrogen-driven transcriptional programs ( Márton et al, 2023 ).…”

Hybrid CTAB–Silica and APTES-Functionalized Multi-Walled Carbon Nanotubes for Adsorption-Enhanced Electrochemical Detection of Bisphenol A in Environmental and Food Samples

“…The use of concentrated PBS promotes desorption of residual BPA and weakly adsorbed species, allowing partial recovery of the electrode surface. 84,85 As shown in Figs. 8a, 8b, the current response remained relatively stable over the five cycles, with a slight decrease observed after the first measurement, resulting in an RSD of 1.30%.…”

Differential Regulation of Genes by the Glucogenic Hormone Asprosin in Ovarian Cancer

“…Following treatment with 100 nM of asprosin, the serous OvCa cell line, SKOV-3, displayed 160 and 173 gene changes, at 4 and 12 h, respectively, when compared with control samples extracted at parallel time points, p < 0.05 and Log2FC > 1. DEGs were identified using the Cuffdiff multiple-testing module [ 28 ]. These changes are mapped in the volcano plots presented in Figure 1 .…”

Bisphenol A and ovarian cancer: emerging evidence and potential biological mechanisms

“…RNA sequencing of normal human ovarian cells exposed to BPA identified differentially expressed genes that were enriched in pathways related to mRNA surveillance, cellular senescence, and transcriptional regulation. These enrichment results suggest candidate biological processes affected by BPA but do not demonstrate direct activation of these pathways or establish their causal involvement in ovarian carcinogenesis ( Zahra et al, 2022 ). Notably, a subset of these BPA-responsive genes overlaps with those regulated by 17β-estradiol (E2), particularly in pathways associated with cell proliferation and migration, suggesting that BPA partially recapitulates estrogen-driven transcriptional programs ( Márton et al, 2023 ).…”

Hybrid CTAB–Silica and APTES-Functionalized Multi-Walled Carbon Nanotubes for Adsorption-Enhanced Electrochemical Detection of Bisphenol A in Environmental and Food Samples

“…The use of concentrated PBS promotes desorption of residual BPA and weakly adsorbed species, allowing partial recovery of the electrode surface. 84,85 As shown in Figs. 8a, 8b, the current response remained relatively stable over the five cycles, with a slight decrease observed after the first measurement, resulting in an RSD of 1.30%.…”

Differential Regulation of Genes by the Glucogenic Hormone Asprosin in Ovarian Cancer

“…Following treatment with 100 nM of asprosin, the serous OvCa cell line, SKOV-3, displayed 160 and 173 gene changes, at 4 and 12 h, respectively, when compared with control samples extracted at parallel time points, p < 0.05 and Log2FC > 1. DEGs were identified using the Cuffdiff multiple-testing module [ 28 ]. These changes are mapped in the volcano plots presented in Figure 1 .…”

Bisphenol A and ovarian cancer: emerging evidence and potential biological mechanisms

“…RNA sequencing of normal human ovarian cells exposed to BPA identified differentially expressed genes that were enriched in pathways related to mRNA surveillance, cellular senescence, and transcriptional regulation. These enrichment results suggest candidate biological processes affected by BPA but do not demonstrate direct activation of these pathways or establish their causal involvement in ovarian carcinogenesis ( Zahra et al, 2022 ). Notably, a subset of these BPA-responsive genes overlaps with those regulated by 17β-estradiol (E2), particularly in pathways associated with cell proliferation and migration, suggesting that BPA partially recapitulates estrogen-driven transcriptional programs ( Márton et al, 2023 ).…”