Interference of estrogen signaling by endocrine disruptors in male and female cells: Potential implications of BPS and PFOS in human development

Endocrine-disruptors (EDs), such as bisphenol-S (BPS) and perfluorooctane-sulfonate (PFOS), can cross the placental barrier and interfere with fetal development, inducing consequences that seem to be more pronounced in males. We investigated whether BPS and PFOS could have different effects on male and female human induced-pluripotent-stem cells (hiPSCs) by analyzing their impact on estrogen signaling pathways. Our results demonstrate that in male hiPSCs, BPS and PFOS induce alterations in the estrogen pathways, confirming their role as xenoestrogens. BPS and PFOS also upregulated oxidative phosphorylation proteins in males, while disruptions in Golgi apparatus integrity were observed in female cells. These findings highlight the differential susceptibility of male and female cells to ED exposure and suggest that such chemicals, perturbing the hormonal network, may affect developmental programming and long-term health. Moreover, this study emphasizes the importance of considering sex-specific responses to environmental pollutants and their impact during the highly sensitive periods of fetal growth.