title: Histone Deacetylase 1 Regulates the Expression of Progesterone Receptor A During Human Parturition by Occupying the Progesterone Receptor A Promoter.
abstract: The functional withdrawal of progesterone is mediated by the enhanced expression ratio of the 2 progesterone receptor (PR) isoforms, PRA and PRB, and causes the pregnant human myometrium to switch from a quiet state to a state of excitation-contraction and subsequent laboring. However, the precise mechanisms responsible for alterations in PRA and PRB expression during human parturition have yet to be resolved. In the present study, we report that PRA expression was increased in myometrium samples during labor (P < .001), concomitant with reduced expression of histone deacetylase 1 (HDAC1; P < .01). These results were further confirmed in the laboratory using cultured primary myometrial cells to investigate the effects of HDAC1 knockdown or overexpression. Finally, we verified that HDAC1 downregulated PRA expression by binding to the promoter region of PRA as confirmed by chromatin immunoprecipitation assays (P < .01) and real-time polymerase chain reaction (P < .001). Therefore, the present study not only demonstrates the epigenetic mechanisms underlying human labor but also provides a potential clinical strategy with which to intervene and prevent labor disorders.
authors.affiliation: Department of Gynecology and Obstetrics, Southwestern Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Weiping
authors.initials: W
authors.lastname: Ke
authors.affiliation: Department of Gynecology and Obstetrics, Southwestern Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Chen
authors.affiliation: Department of Gynecology and Obstetrics, Southwestern Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Luo
authors.affiliation: Department of Dermatology, The 105th Hospital of PLA, Hefei, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Tang
authors.affiliation: Institute of Immunology, PLA, Third Military Medical University, Chongqing, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Institute of Immunology, PLA, Third Military Medical University, Chongqing, China.
authors.forename: Weiwu
authors.initials: W
authors.lastname: Gao
authors.affiliation: Institute of Immunology, PLA, Third Military Medical University, Chongqing, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Yang
authors.affiliation: Institute of Immunology, PLA, Third Military Medical University, Chongqing, China.
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Tian
authors.affiliation: Department of Gynecology and Obstetrics, Southwestern Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Chang
authors.affiliation: Department of Gynecology and Obstetrics, Southwestern Hospital, Third Military Medical University, Chongqing, China 914054186@qq.com cqli99@yahoo.com.
authors.forename: Zhiqing
authors.initials: Z
authors.lastname: Liang
mesh_terms: D000328:Adult; D002478:Cells, Cultured; D005260:Female; D005786:Gene Expression Regulation; D056284:Histone Deacetylase 1 / Q000378:metabolism*; D006801:Humans; D009215:Myometrium / Q000378:metabolism; D036801:Parturition; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000378:metabolism; D011980:Receptors, Progesterone / Q000235:genetics / Q000378:metabolism*
chemical_list: D012333:RNA, Messenger; D011980:Receptors, Progesterone; C101118:progesterone receptor A; C110550:HDAC1 protein, human; D056284:Histone Deacetylase 1
keywords: HDAC1; epigenetic; labor; myometrium; progesterone receptors