{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Moyer HL"],"funding":["National Institute of Environmental Health Sciences","NIEHS NIH HHS","National Institutes of Health","NIGMS NIH HHS"],"pagination":["111782"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12828792"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["421"],"pubmed_abstract":["Epidemiological studies suggest that maternal exposures to environmental pollutants may be linked to spontaneous preterm birth. Mechanistic studies are needed to provide support to these hypotheses; however, existing in vitro models do not replicate human feto-maternal barriers beyond placenta. The recently developed four-cell Feto-Maternal interface Organ-On-Chip (FMi-OOC) model enables studies of chemical effects that are critically important for maintaining full-term pregnancy. We tested four environmental pollutants that have been associated with preterm birth - dichlorodiphenyltrichloroethane (DDT-o,p'), bisphenol A (BPA), 2,2'4,4'-tetrabromodiphenyl ether (PBDE-47), and perfluorooctanoic acid (PFOA). Concentration-response effects of these chemicals were first tested on maternal decidua cells in 96-well plates. Then, using the 4-cell FMi-OOC that mimics the in utero tissue topology, compounds were added to the maternal (i.e., decidua) chamber, and chemical propagation, cell viability, and cytokine production (IL-6, IL-8, GM-CSF, TNF-α) were measured in decidua, chorion trophoblast, amnion mesenchymal, and amnion epithelial cell chambers for up to 72 h. Minimal chemical propagation to the fetal chambers was observed. Treatment-associated increase in cytokines was observed for all compounds tested, with PFOA and BPA showing the strongest effects and amnion epithelial cells being most responsive. We demonstrate how the multi-cellular FMi-OOC can be used to study paracrine signaling in feto-maternal interface tissues. We show that upon maternal exposure, albeit at concentrations exceeding human blood levels by 1-2 orders of magnitude, fetal membranes attain pro-inflammatory state, a trigger for preterm birth. These studies support the biological plausibility of the epidemiological associations between exposures to tested compounds and preterm birth."],"journal":["Chemico-biological interactions"],"pubmed_title":["Fetal response to maternal exposures of environmental chemicals: Utility of a four-cell human feto-maternal interface organ-on-chip."],"pmcid":["PMC12828792"],"funding_grant_id":["P42 ES027704","T32 GM135748","T32 ES026568"],"pubmed_authors":["Kim S","Lin HC","Han A","Richardson LS","Tsai HD","Moyer HL","Menon R","Rusyn I","Ford LC","Lam BP","Chiu WA"],"additional_accession":[]},"is_claimable":false,"name":"Fetal response to maternal exposures of environmental chemicals: Utility of a four-cell human feto-maternal interface organ-on-chip.","description":"Epidemiological studies suggest that maternal exposures to environmental pollutants may be linked to spontaneous preterm birth. Mechanistic studies are needed to provide support to these hypotheses; however, existing in vitro models do not replicate human feto-maternal barriers beyond placenta. The recently developed four-cell Feto-Maternal interface Organ-On-Chip (FMi-OOC) model enables studies of chemical effects that are critically important for maintaining full-term pregnancy. We tested four environmental pollutants that have been associated with preterm birth - dichlorodiphenyltrichloroethane (DDT-o,p'), bisphenol A (BPA), 2,2'4,4'-tetrabromodiphenyl ether (PBDE-47), and perfluorooctanoic acid (PFOA). Concentration-response effects of these chemicals were first tested on maternal decidua cells in 96-well plates. Then, using the 4-cell FMi-OOC that mimics the in utero tissue topology, compounds were added to the maternal (i.e., decidua) chamber, and chemical propagation, cell viability, and cytokine production (IL-6, IL-8, GM-CSF, TNF-α) were measured in decidua, chorion trophoblast, amnion mesenchymal, and amnion epithelial cell chambers for up to 72 h. Minimal chemical propagation to the fetal chambers was observed. Treatment-associated increase in cytokines was observed for all compounds tested, with PFOA and BPA showing the strongest effects and amnion epithelial cells being most responsive. We demonstrate how the multi-cellular FMi-OOC can be used to study paracrine signaling in feto-maternal interface tissues. We show that upon maternal exposure, albeit at concentrations exceeding human blood levels by 1-2 orders of magnitude, fetal membranes attain pro-inflammatory state, a trigger for preterm birth. These studies support the biological plausibility of the epidemiological associations between exposures to tested compounds and preterm birth.","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Nov","modification":"2026-06-06T22:08:51.041Z","creation":"2026-06-05T03:12:19.207Z"},"accession":"S-EPMC12828792","cross_references":{"pubmed":["41106448"],"doi":["10.1016/j.cbi.2025.111782"]}}