Potential role of endocrine-disrupting chemicals in preeclampsia: A hypothesis based on integration of epidemiological and experimental evidence

Abstract

Preeclampsia (PE) is a complex hypertensive disorder and a leading cause of maternal and perinatal morbidity worldwide. Emerging evidence suggests that exposure to endocrine-disrupting chemicals (EDCs) may contribute to the etiology of PE, yet this association remains underexplored. This review aimed to investigate epidemiological and experimental studies assessing the potential link between EDC exposure and PE development. A literature search was conducted across PubMed, ScienceDirect, and Google Scholar for original articles published in the last ten years. Forty studies were selected, including epidemiological cohorts, in vivo, and in vitro models, focusing on the association between EDCs and PE or related biomarkers. Epidemiological findings were heterogeneous: while large cohorts often showed no association, several case-control studies linked specific EDCs, such as bisphenol A, phthalates, cadmium, and PFOS, to increased PE risk and elevated blood pressure. Experimental evidence revealed that EDCs impair key placental processes, including decidualization, angiogenesis, and trophoblast invasion. These disruptions were often accompanied by oxidative stress, hormonal imbalances, and endothelial dysfunction, central features in PE pathogenesis. In vivo models also replicated PE-like syndrome after EDC exposure. Although current epidemiological evidence remains inconsistent, mechanistic studies strongly support the biological plausibility of EDC involvement in PE. This review highlights that the contribution of EDCs to PE may be underestimated and calls for multidisciplinary research to clarify exposure thresholds, vulnerable windows, and population-specific susceptibilities.