{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T23:36:12Z","timestamp":1787009772364,"version":"build-2736575974"},"reference-count":65,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2021,8,12]],"date-time":"2021-08-12T00:00:00Z","timestamp":1628726400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2021,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Normal pregnancy is essential for human reproduction. However, BaP (benzo(a)pyrene) and its metabolite BPDE (benzo(a)pyrene\u20107,8\u2010dihydrodiol\u20109,10\u2010epoxide) could cause dysfunctions of human trophoblast cells and might further induce miscarriage. Yet, the underlying mechanisms remain largely unknown. Herein, we identified a novel upregulated lnc\u2010HZ04 and a novel downregulated miR\u2010hz04 in villous tissues of unexplained recurrent miscarriage (RM) relative to those in healthy control tissues and also in BPDE\u2010treated human trophoblast cells. Lnc\u2010HZ04 directly and specifically bound with miR\u2010hz04, diminished the reduction effects of miR\u2010hz04 on IP\n                    <jats:sub>3<\/jats:sub>\n                    R\n                    <jats:sub>1<\/jats:sub>\n                    mRNA expression level and on IP\n                    <jats:sub>3<\/jats:sub>\n                    R\n                    <jats:sub>1<\/jats:sub>\n                    mRNA stability, and then activated the Ca\n                    <jats:sup>2+<\/jats:sup>\n                    \u2010mediated IP\n                    <jats:sub>3<\/jats:sub>\n                    R\n                    <jats:sub>1<\/jats:sub>\n                    \/p\u2010CaMKII\/SGCB pathway, which further promoted trophoblast cell apoptosis. The miR\u2010hz04 target site on lnc\u2010HZ04 played crucial roles in these regulations. In normal trophoblast, relatively less lnc\u2010HZ04 and more miR\u2010hz04 suppressed this apoptosis pathway and gave normal pregnancy. After exposure to BPDE or in RM tissues, p53 was upregulated, which might promote p53\u2010mediated lnc\u2010HZ04 transcription. Relatively more lnc\u2010HZ04 and less miR\u2010hz04 activated this apoptosis pathway and might further induce miscarriage. BaP could also induce mice miscarriage by upregulating its corresponding murine apoptosis pathway. Therefore, BPDE\u2010induced apoptosis of human trophoblast cells was associated with the occurrence of miscarriage. This work discovered the regulation roles of lnc\u2010HZ04 and miR\u2010hz04 and provided scientific and clinical understanding of the occurrence of unexplained miscarriage.\n                  <\/jats:p>","DOI":"10.1096\/fj.202100376rr","type":"journal-article","created":{"date-parts":[[2021,8,12]],"date-time":"2021-08-12T13:28:27Z","timestamp":1628774907000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Novel lncRNA\u2010HZ04 promotes BPDE\u2010induced human trophoblast cell apoptosis and miscarriage by upregulating IP\n                    <sub>3<\/sub>\n                    R\n                    <sub>1<\/sub>\n                    \/CaMKII\/SGCB pathway by competitively binding with miR\u2010hz04"],"prefix":"10.1096","volume":"35","author":[{"given":"Wenxin","family":"Huang","sequence":"first","affiliation":[{"name":"Research Center for Environment and Female Reproductive Health The Eighth Affiliated Hospital, Sun Yat\u2010sen University Shenzhen China"},{"name":"Department of Toxicology, School of Public Health Fujian Medical University Fuzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengyuan","family":"Dai","sequence":"additional","affiliation":[{"name":"Research Center for Environment and Female Reproductive Health The Eighth Affiliated Hospital, Sun Yat\u2010sen University Shenzhen China"},{"name":"Department of Toxicology, School of Public Health Fujian Medical University Fuzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taotao","family":"Qiu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Environment and Female Reproductive Health West China School of Public Health &amp; West China Fourth Hospital, Sichuan University Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tingting","family":"Liang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Environment and Female 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