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However, whether the defective homologous recombination (HR) repair of dsDNA break (DSB) in trophoblast cells may induce miscarriage is completely unknown. Moreover, the abundance of BRCA1 (a crucial protein for HR repair), its recruitment to DSB foci, and its epigenetic regulatory mechanisms, are also fully unexplored. In this work, it is identified that a novel lnc\u2010HZ10, which is highly experssed in villous tissues of recurrent miscarriage (RM) vs their healthy control group, suppresses HR repair of DSB in trophoblast cell. Lnc\u2010HZ10 and AhR (aryl hydrocarbon receptor) form a positive feedback loop. AhR acts as a transcription factor to promote lnc\u2010HZ10 transcription. Meanwhile, lnc\u2010HZ10 also increases AhR levels by suppressing its CUL4B\u2010mediated ubiquitination degradation. Subsequently, AhR suppresses BRCA1 transcription; and lnc\u2010HZ10 (mainly 1\u2010447 nt) interacts with \u03b3\u2010H2AX; and thus, impairs its interactions with BRCA1. BPDE exposure may trigger this loop to suppress HR repair in trophoblast cells, possibly inducing miscarriage. Knockdown of murine Ahr efficiently recovers HR repair in placental tissues and alleviates miscarriage in a mouse miscarriage model. Therefore, it is suggested that AhR\/lnc\u2010HZ10\/BRCA1 axis may be a promising target for alleviation of unexplained miscarriage.<\/jats:p>","DOI":"10.1002\/advs.202207435","type":"journal-article","created":{"date-parts":[[2024,1,29]],"date-time":"2024-01-29T21:33:46Z","timestamp":1706564026000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Defective Homologous Recombination Repair By Up\u2010Regulating Lnc\u2010HZ10\/Ahr Loop in Human Trophoblast Cells Induced Miscarriage"],"prefix":"10.1002","volume":"11","author":[{"given":"Weina","family":"Chen","sequence":"first","affiliation":[{"name":"Research Center for Environment and Female Reproductive Health The Eighth Affiliated Hospital Sun Yat\u2010sen University  Shenzhen 518033 China"},{"name":"Key Laboratory of Environment and Female Reproductive Health West China School of Public Health &amp; West China Fourth Hospital Sichuan University  Chengdu 610041 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