title: Endogenous hydrogen sulfide contributes to uterine quiescence during pregnancy.
abstract: Recent evidence suggests that uterine activation for labor is associated with inflammation within uterine tissues. Hydrogen sulfide (H2S) plays a critical role in inflammatory responses in various tissues. Our previous study has shown that human myometrium produces H2S via its generating enzymes cystathionine-γ-lyase (CSE) and cystathionine-β-synthetase (CBS) during pregnancy. We therefore explored whether H2S plays a role in the maintenance of uterine quiescence during pregnancy. Human myometrial biopsies were obtained from pregnant women at term. Uterine smooth muscle cells (UMSCs) isolated from myometrial tissues were treated with various reagents including H2S. The protein expression of CSE, CBS and contraction-associated proteins (CAPs) including connexin 43, oxytocin receptor and prostaglandin F2αreceptor determined by Western blot. The levels of cytokines were measured by ELISA. The results showed that CSE and CBS expression inversely correlated to the levels of CAPs and activated NF-κB in pregnant myometrial tissues. H2S inhibited the expression of CAPs, NF-κB activation and the production of interleukin (IL)-1β, IL-6 and tumor necrosis factor α (TNFα) in cultured USMCs. IL-1β treatment reversed H2S inhibition of CAPs. Knockdown of CSE and CBS prevented H2S suppression of inflammation. H2S modulation of inflammation is through KATPchannels and phosphoinositide 3-kinase (PI3K) and extracellular signal-regulated kinase (ERK) signaling pathways. H2S activation of PI3K and ERK signaling is dependent on KATPchannels. Our data suggest that H2S suppresses the expression of CAPs via inhibition of inflammation in myometrium. Endogenous H2S is one of the key factors in maintenance of uterine quiescence during pregnancy.
authors.affiliation: Department of Physiology.
authors.forename: Xingji
authors.initials: X
authors.lastname: You
authors.affiliation: Department of Physiology.
authors.forename: Zixi
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Department of Obstetrics and GynecologyChanghai Hospital, Second Military Medical University, Shanghai, China.|Department of Obstetrics and GynecologySeventh People's Hospital of Shanghai University of Traditional Chinese Medicine, Shanghai, China.
authors.forename: Huina
authors.initials: H
authors.lastname: Zhao
authors.affiliation: Department of Physiology.
authors.forename: Chen
authors.initials: C
authors.lastname: Xu
authors.affiliation: Department of Physiology.
authors.forename: Weina
authors.initials: W
authors.lastname: Liu
authors.affiliation: Department of Obstetrics and GynecologyChanghai Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Qianqian
authors.initials: Q
authors.lastname: Sun
authors.affiliation: Department of Physiology.
authors.forename: Ping
authors.initials: P
authors.lastname: He
authors.affiliation: Department of Obstetrics and GynecologyChanghai Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Hang
authors.initials: H
authors.lastname: Gu
authors.affiliation: Department of Physiology nixin@smmu.edu.cn.
authors.forename: Xin
authors.initials: X
authors.lastname: Ni
mesh_terms: D000393:Air Pollutants / Q000494:pharmacology*; D002478:Cells, Cultured; D003542:Cystathionine gamma-Lyase / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D006862:Hydrogen Sulfide / Q000494:pharmacology*; D007249:Inflammation / Q000188:drug therapy* / Q000378:metabolism; D007743:Labor, Obstetric / Q000187:drug effects* / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009215:Myometrium / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011247:Pregnancy; D015398:Signal Transduction / Q000187:drug effects; D014590:Uterine Contraction / Q000187:drug effects* / Q000378:metabolism; D014599:Uterus / Q000187:drug effects* / Q000378:metabolism
chemical_list: D000393:Air Pollutants; D016207:Cytokines; D016328:NF-kappa B; D019869:Phosphatidylinositol 3-Kinases; D048049:Extracellular Signal-Regulated MAP Kinases; D003542:Cystathionine gamma-Lyase; D006862:Hydrogen Sulfide