02194nas a2200277   4500000000100000000000100001008004100002260001500043100002000058700002500078700002500103700001600128700001400144700002000158700002100178700002200199700001300221700001500234700001900249245012600268856007000394300001400464490000700478520141700485022001401902       2024                            d  c2024-03-121 aManuel S. Vidal1 aLauren S. Richardson1 aAnanth Kumar Kammala1 aSungjin Kim1 aPo Yi Lam1 aRahul Cherukuri1 aTilu Jain Thomas1 aMohammed Bettayeb1 aArum Han1 aIvan Rusyn1 aRamkumar Menon00aEndocrine-disrupting compounds and their impact on human placental function: evidence from placenta organ-on-chip studies  uhttps://pubs.rsc.org/en/content/articlelanding/2024/lc/d3lc00998j  a1727-17490 v243 aThe effects of endocrine-disrupting compounds (EDCs) on the placenta, a critical gestational organ for xenobiotic protection, are well reported; however, models to determine the role of EDCs in placental disruption are limited. An advanced 2nd-trimester human placenta organ-on-chip model (2TPLA-OOC) was developed and validated, with six representative cells of the maternal and the fetal interface interconnected with microchannels. Various EDCs (150 ng mL−1 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.  a1473-0189