Bisphenol A Interferes with Mast Cell-Mediated Promotion of Cellular Processes Critical for Spiral Artery Remodeling

TL;DR

Bisphenol A disrupts mast cell support for critical pregnancy-related blood vessel changes, potentially harming reproductive health.

Contribution

This study identifies bisphenol A as a disruptor of mast cell-mediated processes essential for spiral artery remodeling during pregnancy.

Findings

BPA exposure reduced mast cell promotion of trophoblast invasion and vascular smooth muscle cell transition.

High BPA doses altered gene expression related to mast cell activation and trophoblast invasion.

Low BPA doses increased pro-inflammatory mediator expression in mast cells without affecting trophoblasts.

Abstract

Mast cells (MCs) belong to the cell network that regulates uterine spiral artery remodeling (uSAR), a critical vascular adaptation supporting placental development and fetal growth. Our previous in vitro study demonstrated that human MCs promote trophoblast invasion, as well as uterine vascular smooth muscle cells (uVSMCs) migration and transition to a synthetic phenotype—essential steps for a successful uSAR. Although MCs are known targets of bisphenol A (BPA), a widespread endocrine-disrupting chemical, its impact on their supportive role in uSAR is unknown. In this study, we used murine cell lines to investigate whether BPA (0.1–100 µM) affects MC-mediated promotion of cellular processes critical for uSAR. Our results showed that BPA exposure hindered MCs’ ability to promote trophoblast invasion and the switch in uVSMCs’ synthetic phenotype and migration. The highest concentrations of BPA altered the expression of genes related to MCs activation and proliferation, and of those involved in trophoblasts invasion. In contrast, low doses induced the expression of pro-inflammatory mediators in MCs without detectable effect on trophoblasts at the transcriptional level. These findings confirmed MCs as key mediators of uSAR, and identified BPA as a disruptor of their function, emphasizing its potential harmful impact on reproductive health.

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