title: Characterization of two labor-induced genes, DSCR1 and TCTE1L, in the pregnant ovine myometrium.
abstract: In the present study we characterized two labor-induced genes, DSCR1 (Down syndrome candidate region 1) and TCTE1L (murine t-complex like), which were identified by suppression subtractive hybridization in the pregnant ovine myometrium. DSCR1 and TCTE1L cDNA sequences were retrieved from a custom-made labor-myometrial cDNA library by hybridization screening. The characterized cDNA sequences include 5'-untranslated region (UTR), coding region and 3'-UTR, which are 12 bp, 351 bp and 1716 bp for TCTE1L, and 64 bp, 594 bp and 1539 bp for DSCR1 respectively. The two cDNA sequences encode proteins of 116 and 197 amino acids for TCTE1L and DSCR1 respectively. Northern analysis further confirmed the significant increases of myometrial DSCR1 and TCTE1L mRNA associated with spontaneous term labor (n=6) compared with gestation-matched controls not in labor (n=6). The abundance of DSCR1 and TCTE1L mRNA was attenuated when myometrial contraction was inhibited by Nimesulide (n=6), a specific prostaglandin H synthase 2 inhibitor. Fetal occupancy greatly upregulated DSCR1 and TCTE1L mRNA in the gravid horn during betamethasone-induced premature labor (n=6) compared with the non-gravid horn not in labor (n=3). Estradiol upregulated TCTE1L mRNA, but had no effect on DSCR1 mRNA expression in the non-pregnant sheep myometrium. Progesterone alone had no effect on both DSCR1 and TCTE1L mRNA expression, however progesterone antagonized estradiol's stimulating effect on myometrial TCTE1L mRNA expression in ovariectomized non-pregnant sheep. Upregulation of DSCR1 and TCTE1L in both betamethasone-induced premature labor and spontaneous term labor and inhibition of their expression by Nimesulide suggest a functional role of these two genes in myometrial activation associated with onset of labor. Mechanical stretch, labor and steroids differentially regulated DSCR1 and TCTE1L mRNA in the pregnant and non-pregnant sheep myometrium.
authors.affiliation: Department of Obstetrics and Gynecology, RP1, Suite 470, 800 N. Research Parkway, The University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73104, USA. WWu1@ouhsc.edu
authors.forename: W X
authors.initials: WX
authors.lastname: Wu
authors.forename: X H
authors.initials: XH
authors.lastname: Ma
authors.forename: Q
authors.initials: Q
authors.lastname: Zhang
authors.forename: K
authors.initials: K
authors.lastname: Chakrabarty
authors.forename: P W
authors.initials: PW
authors.lastname: Nathanielsz
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001623:Betamethasone / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004268:DNA-Binding Proteins; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D005786:Gene Expression Regulation; D015723:Gene Library; D005938:Glucocorticoids / Q000494:pharmacology; D006801:Humans; D017403:In Situ Hybridization / Q000379:methods; D047908:Intracellular Signaling Peptides and Proteins; D007743:Labor, Obstetric / Q000378:metabolism*; D008869:Microtubule-Associated Proteins / Q000235:genetics*; D008969:Molecular Sequence Data; D009124:Muscle Proteins / Q000235:genetics*; D009215:Myometrium / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics*; D011247:Pregnancy; D011374:Progesterone / Q000494:pharmacology; D017386:Sequence Homology, Amino Acid; D012756:Sheep / Q000378:metabolism*; D013449:Sulfonamides / Q000494:pharmacology; D044767:Ubiquitin-Protein Ligases; D014590:Uterine Contraction; D056427:t-Complex Genome Region
chemical_list: D016861:Cyclooxygenase Inhibitors; D004268:DNA-Binding Proteins; D005938:Glucocorticoids; D047908:Intracellular Signaling Peptides and Proteins; D008869:Microtubule-Associated Proteins; D009124:Muscle Proteins; D009687:Nuclear Proteins; C108612:RCAN1 protein, human; D013449:Sulfonamides; D011374:Progesterone; D004958:Estradiol; D001623:Betamethasone; C116196:PPP1R11 protein, human; D044767:Ubiquitin-Protein Ligases; C012655:nimesulide