Endocrine-disrupting compounds and their impact on human placental function: evidence from placenta organ-on-chip studies
Manuel S. Vidal, Lauren Richardson, Ananth Kumar Kammala, Sungjin Kim, Po Yi Lam, Rahul Cherukuri, Tilu Jain Thomas, Mohammed Bettayeb, Arum Han, Ivan Rusyn, Ramkumar Menon
Abstract
each of bisphenol A, bisphenol S, and polybrominated diphenyl ethers-47 and -99) were gradually propagated across the chip for 72 hours, and their various effects were determined. Cigarette smoke extract (CSE), an environmental risk factor, was used as a positive control. EDCs produced overall oxidative stress in the placental/decidual cells, induced cell-specific endocrine effects, caused limited (<10%) apoptosis/necrosis in trophoblasts and mesenchymal cells, induced localized inflammation but an overall anti-inflammatory shift, did not change immune cell migration from stroma to decidua, and did not affect placental nutrient transport. Overall, (1) the humanized 2TPLA-OOC recreated the placental organ and generated data distinct from the trophoblast and other cells studied in isolation, and (2) at doses associated with adverse pregnancies, EDCs produced limited and localized insults, and the whole organ compensated for the exposure.