title: Lefty inhibits in vitro decidualization by regulating P57 and cyclin D1 expressions.
abstract: Endometrial decidualization is highly important for successful construction and maintenance of embryo implantation and pregnancy. Lefty gene at different menstrual cycle phases has different expressions, indicating its regulatory significance. To study the mechanism of Lefty in decidualization, human endometrial stromal cells (hESCs) were cultured and induced with medroxyprogesterone acetate (MPA) and 8-bromoadenosine-cAMP (8-Br-cAMP) in vitro as a research model. Our results showed that Lefty1 overexpression inhibited MPA- and 8-Br-cAMP-induced hESC decidualization and significantly reduced the secretion of prolactin (PRL) and insulin-like growth factor-binding protein 1 (IGFBP-1). With the inhibition of Lefty1 expression, hESC decidualization induced by MPA and 8-Br-cAMP became more remarkable, and the secretions of PRL and IGFBP-1 were higher too. Further tests indicated that during the process of decidualization, P57 expression increased, whereas cyclin D1 expression decreased. Although Lefty1 overexpression did not significantly change the expressions of P57 and cyclin D1, inhibition of Lefty1 expression resulted in more evident changes in P57 and cyclin D1 expressions. Meanwhile, cell cycle examination showed that Lefty1 overexpression reduced the cell cycle arrest at G1/S phase in the in vitro hESC decidualization model. Therefore, Lefty1 could regulate the cell cycle via modulating the expressions of P57 and cyclin D1 and then inhibit the decidualization in vitro.
authors.affiliation: Obstetric Department, ShengJing Hospital of China Medical University, Shenyang, China; Obstetric Department, The Maternity Hospital of Dalian, Dalian, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Li
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.forename: Liang
authors.initials: L
authors.lastname: Bai
authors.forename: Hua
authors.initials: H
authors.lastname: Yu
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D018797:Cell Cycle Proteins / Q000378:metabolism; D019938:Cyclin D1 / Q000235:genetics* / Q000378:metabolism; D050761:Cyclin-Dependent Kinase Inhibitor p57 / Q000235:genetics* / Q000378:metabolism; D033301:Deciduoma / Q000187:drug effects / Q000378:metabolism*; D004717:Endometrium / Q000166:cytology; D005260:Female; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects; D006801:Humans; D055458:Left-Right Determination Factors / Q000235:genetics / Q000378:metabolism*; D008525:Medroxyprogesterone / Q000494:pharmacology; D059807:S Phase Cell Cycle Checkpoints / Q000187:drug effects; D017154:Stromal Cells / Q000378:metabolism
chemical_list: C493964:CDKN1C protein, human; D018797:Cell Cycle Proteins; D050761:Cyclin-Dependent Kinase Inhibitor p57; C526161:LEFTY1 protein, human; D055458:Left-Right Determination Factors; D019938:Cyclin D1; C036038:8-bromoadenosine; D008525:Medroxyprogesterone; D000241:Adenosine
keywords: Lefty; P57; cyclin D1; decidualization; endometrial stromal cells