biostudies-literatureWang MShenzhen Science and Technology Innovation ProgramHebei Provincial Natural Science FoundationBasic and Applied Basic Research Foundation of Guangdong ProvinceNational Natural Science Foundation of China105968https://www.ebi.ac.uk/biostudies/studies/S-EPMC12595282biostudies-literatureUnknown121<h4>Background</h4>Unexplained miscarriage (UM) occurs frequently and significantly limits global human reproduction. However, till now, whether environment-gene interactions might interactively regulate UM has not been well characterised.<h4>Methods</h4>We combined epidemiological study using a UM case-control group and in vitro functional assays using mouse model and human trophoblast HTR-8/SVneo cells. The interactions between environmental exposure to Bisphenol F (BPF) and genetic variation in TLR4 rs4986790 (A896G) were explored. Trophoblast cell migration and invasion (key functions for healthy pregnancy), the interactions between TLR4 variants and β2GPI (β-2 glycoprotein I, an inflammatory mediator), and the downstream signalling molecules MMP9 and RAC1 were investigated.<h4>FindingEBioMedicineInteractive effects of Bisphenol F exposure and TLR4 rs4986790 on unexplained miscarriage.PMC12595282JCYJ20220818103607015B2024201087JCYJ202205301444030082023B1515120054JCYJ20240813180400002JCYJ20230807111401002JCYJ20241202152800001823736022023A1515110497Wu LZhang HLin YFan QCheng WSun YWang MZhang ZHuang WGuo GHuang XChen WXing SZhao DWang YYue XfalseInteractive effects of Bisphenol F exposure and TLR4 rs4986790 on unexplained miscarriage.<h4>Background</h4>Unexplained miscarriage (UM) occurs frequently and significantly limits global human reproduction. However, till now, whether environment-gene interactions might interactively regulate UM has not been well characterised.<h4>Methods</h4>We combined epidemiological study using a UM case-control group and in vitro functional assays using mouse model and human trophoblast HTR-8/SVneo cells. The interactions between environmental exposure to Bisphenol F (BPF) and genetic variation in TLR4 rs4986790 (A896G) were explored. Trophoblast cell migration and invasion (key functions for healthy pregnancy), the interactions between TLR4 variants and β2GPI (β-2 glycoprotein I, an inflammatory mediator), and the downstream signalling molecules MMP9 and RAC1 were investigated.<h4>Finding2025-01-01T00:00:00Z2025 Nov2026-06-05T14:50:04.488Z2026-05-18T03:08:34.368ZS-EPMC125952824113866710.1016/j.ebiom.2025.105968