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While xenobiotic transfer is primarily studied through maternal\u2010fetal comparisons at delivery, its spatiotemporal distribution across gestation stages, particularly the transport mechanisms in early pregnancy, remains poorly understood. In this study, we reveal spatiotemporal heterogeneity of hydrophobic toxicants (including persistent organic pollutants such as medium\u2010chain chlorinated paraffins [MCCPs] and hexabromocyclododecane) and endogenous metabolites in the developing placenta and fetus by mass spectrometry imaging (MSI). The stage of transition to hemotrophic nutrition is found as a critical window with fetal\u2010to\u2010maternal distribution ratios of xenobiotics approximately 8.4\u201338.2\u2010times higher than those estimated at birth. At this critical stage, Scavenger Receptor Class B Member 1 (SR\u2010B1) is identified as the key, stage\u2010specific, and predominate transporter mediating fetal delivery of hydrophobic toxicants and lipids in early gestation through integration of spatial metabolomics and single\u2010nucleus RNA sequencing of placental tissue. Finally, our findings demonstrate that early gestational exposure to MCCPs is associated with fetal neuro\u2010lipotoxicity. The results highlight the urgent need to reduce early\u2010pregnancy xenobiotic exposure for preventing toxicant\u2010associated fetal lipid metabolic disruption.<\/jats:p>","DOI":"10.1002\/advs.202515742","type":"journal-article","created":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T13:19:26Z","timestamp":1772975966000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["SR\u2010B1\u2010Mediated Transplacental Transfer of Hydrophobic Toxicants Disrupts Fetal Development During Barriergenesis"],"prefix":"10.1002","volume":"13","author":[{"given":"Yixuan","family":"Huang","sequence":"first","affiliation":[{"name":"Laboratory For Earth Surface Processes College of Urban and Environmental Sciences Peking University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hailin","family":"Shang","sequence":"additional","affiliation":[{"name":"Laboratory For Earth Surface Processes College of 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