{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T20:42:40Z","timestamp":1781642560205,"version":"3.54.5"},"reference-count":22,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2019,10,12]],"date-time":"2019-10-12T00:00:00Z","timestamp":1570838400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Disruption of circadian rhythms is associated with aberrant trophoblast migration and invasion in recurrent spontaneous abortion (RSA). This study aims to explore the functional role and the mechanisms of cryptochrome 2 (CRY2), a fundamental component of the circadian clock, in regulating trophoblast migration and invasion. Human extravillous trophoblast cell line HTR-8\/SVneo was used as a cell model. Cell migration and invasion were examined using wound healing assay and Transwell assay, respectively. The mRNA and protein levels were determined using quantitative real-time polymerase chain reaction and western blot, respectively. Luciferase reporter assay and chromatin immunoprecipitation assay were performed to explore the interaction between c-Myc to the brain and muscle ARNT-like protein 1 (BMAL1) promoter. CRY2 was highly expressed in human villous specimens of RSA. Furthermore, CRY2 overexpression impaired migration and invasion in HTR-8\/SVneo cells, whereas CRY2 knockdown yielded the opposite results. Mechanistically, c-Myc bound to the BMAL1 promoter and induced BMAL1 transcription, both of which further activated matrix metalloproteinase 2\/9 (MMP2\/9) and facilitated migration and invasion in HTR-8\/SVneo cells. CRY2 inhibited c-Myc-BMAL1 pathway and impaired migration and invasion of HTR-8\/SVneo cells. Collectively, these findings demonstrate that CRY2 suppresses trophoblast migration and invasion via inhibiting c-Myc-BMAL1-MMP2\/9 pathway.<\/jats:p>","DOI":"10.1093\/jb\/mvz076","type":"journal-article","created":{"date-parts":[[2019,9,16]],"date-time":"2019-09-16T11:48:00Z","timestamp":1568634480000},"page":"79-87","source":"Crossref","is-referenced-by-count":28,"title":["CRY2 suppresses trophoblast migration and invasion in recurrent spontaneous abortion"],"prefix":"10.1093","volume":"167","author":[{"given":"Lianzhi","family":"Wu","sequence":"first","affiliation":[{"name":"Department of Obstetric, Renmin Hospital of Wuhan University, No. 99 Zhangzhidong Road, Wuchang District, Wuhan, Hubei Province, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Biheng","family":"Cheng","sequence":"first","affiliation":[{"name":"Department of Obstetric, Renmin Hospital of Wuhan University, No. 99 Zhangzhidong Road, Wuchang District, Wuhan, Hubei Province, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Obstetric, Renmin Hospital of Wuhan University, No. 99 Zhangzhidong Road, Wuchang District, Wuhan, Hubei Province, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Jiang","sequence":"first","affiliation":[{"name":"Department of Obstetric, Renmin Hospital of Wuhan University, No. 99 Zhangzhidong Road, Wuchang District, Wuhan, Hubei Province, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Yang","sequence":"first","affiliation":[{"name":"Reproductive Medical Center, Renmin Hospital of Wuhan University, No. 99 Zhangzhidong Road, Wuchang District, Wuhan, Hubei Province, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,10,12]]},"reference":[{"key":"2020032004574690000_mvz076-B1","doi-asserted-by":"crossref","first-page":"79","DOI":"10.4103\/2229-516X.179024","article-title":"Endocrine dysfunction and recurrent spontaneous abortion: an overview","volume":"6","author":"Kaur","year":"2016","journal-title":"Int. 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