biostudies-literatureVan Buren ENIEHS NIH HHSNIAID NIH HHSU.S. Department of Health & Human Services | NIH | National Institute of Environmental Health SciencesU.S. Department of Health & Human Services | NIH | National Institute of Environmental Health Sciences (NIEHS)NHGRI NIH HHS6549https://www.ebi.ac.uk/biostudies/studies/S-EPMC11297347biostudies-literatureUnknown15(1)The placenta is crucial for fetal development, yet the impact of environmental stressors such as arsenic exposure remains poorly understood. We apply single-cell RNA sequencing to analyze the response of the mouse placenta to arsenic, revealing cell-type-specific gene expression, function, and pathological changes. Notably, the Prap1 gene, which encodes proline-rich acidic protein 1 (PRAP1), is significantly upregulated in 26 placental cell types including various trophoblast cells. Our study shows a female-biased increase in PRAP1 in response to arsenic and localizes it in the placenta. In vitro and ex vivo experiments confirm PRAP1 upregulation following arsenic treatment and demonstrate that recombinant PRAP1 protein reduces arsenic-induced cytotoxicity and downregulates cell cycle pathways in human trophoblast cells. Moreover, PRAP1 knockdown differentially affects cell cycle processes, proliferation, and cell death depending on the presence of arsenic. Our findings provide insights into the placental response to environmental stress, offering potential preventative and therapeutic approaches for environment-related adverse outcomes in mothers and children.Nature communicationsSingle-cell RNA sequencing reveals placental response under environmental stress.PMC11297347P42 ES030990T32 ES007026P30 ES001247P30ES001247R00ES029548R00 ES029548K99 ES029548U01 HG012064R01 AI111914T32 ES007142Park HRRangel-Moreno JAzzara DMurphy SPCohen EDLin XGarcia-Hernandez MLLewis EVan Buren EfalseSingle-cell RNA sequencing reveals placental response under environmental stress.The placenta is crucial for fetal development, yet the impact of environmental stressors such as arsenic exposure remains poorly understood. We apply single-cell RNA sequencing to analyze the response of the mouse placenta to arsenic, revealing cell-type-specific gene expression, function, and pathological changes. Notably, the Prap1 gene, which encodes proline-rich acidic protein 1 (PRAP1), is significantly upregulated in 26 placental cell types including various trophoblast cells. Our study shows a female-biased increase in PRAP1 in response to arsenic and localizes it in the placenta. In vitro and ex vivo experiments confirm PRAP1 upregulation following arsenic treatment and demonstrate that recombinant PRAP1 protein reduces arsenic-induced cytotoxicity and downregulates cell cycle pathways in human trophoblast cells. Moreover, PRAP1 knockdown differentially affects cell cycle processes, proliferation, and cell death depending on the presence of arsenic. Our findings provide insights into the placental response to environmental stress, offering potential preventative and therapeutic approaches for environment-related adverse outcomes in mothers and children.2024-01-01T00:00:00Z2024 Aug2026-06-05T06:27:12.307Z2025-02-19T02:27:21.135ZS-EPMC112973473909538510.1038/s41467-024-50914-9