title: Prolonged pregnancy in women is associated with attenuated myometrial expression of progesterone receptor co-regulator Krüppel-like Factor 9.
abstract: BACKGROUND
  Late-term pregnancy may lead to maternal and neonatal morbidity and mortality. Mice null for the progesterone receptor co-regulator Krüppel-like Factor 9 (KLF9) exhibit delayed parturition and increased incidence of neonatal deaths.
  
  
  OBJECTIVE
  Our aim is to evaluate the contribution of myometrial KLF9 to human parturition.
  
  
  METHODS
  Myometrial biopsies were obtained from women with term (>37 to ≤41 wk) and late-term (>41 wk) pregnancies during cesarean delivery and assessed for gene and protein expression. Human myometrial cells transfected with nontargeting or KLF9 small interfering RNAs (siRNA) were treated with the progesterone antagonist RU486 and analyzed for pro-inflammatory chemokine/cytokine gene expression.
  
  
  METHODS
  The study took place in a University-affiliated tertiary care hospital and University research laboratory.
  
  
  METHODS
  Term patients (n = 8) were in spontaneous active labor whereas late-term patients (n = 5) were either in or were induced to active labor, prior to elective cesarean delivery.
  
  
  METHODS
  Steroid hormone receptor, contractility, and inflammation-associated gene expression in myometrial biopsies and in siKLF9-transfected, RU486-treated human myometrial cells was associated with KLF9 expression levels.
  
  
  RESULTS
  Myometrium from women with late-term pregnancy showed lower KLF9, total PGR, and PGR-A/PGR-B isoform expression. Transcript levels of select chemokines/cytokines were up- (CSF3, IL1, IL12A, TGFB2) and down- (CCL3, CCL5, CXCL1, CXCL5, IL15) regulated in late-term relative to term myometrium. Knock-down of KLF9 expression in RU486-treated human myometrial cells modified the expression of PGR and labor-associated cytokines, relative to control siRNA-treated cells.
  
  
  CONCLUSIONS
  Myometrial KLF9 may contribute to the onset of human parturition through its regulation of PGR expression and inflammatory signaling networks.
authors.affiliation: Department of Physiology and Biophysics (J.M.P.P., F.A.S., R.C.M.S.), University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205; and Department of Obstetrics and Gynecology (D.Z., D.S.G.), Crozer-Chester Medical Center, Upland, Pennsylvania 19013.
authors.forename: John Mark P
authors.initials: JM
authors.lastname: Pabona
authors.forename: Daying
authors.initials: D
authors.lastname: Zhang
authors.forename: David S
authors.initials: DS
authors.lastname: Ginsburg
authors.forename: Frank A
authors.initials: FA
authors.lastname: Simmen
authors.forename: Rosalia C M
authors.initials: RC
authors.lastname: Simmen
mesh_terms: D000328:Adult; D002460:Cell Line; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006727:Hormone Antagonists / Q000494:pharmacology; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015735:Mifepristone / Q000494:pharmacology; D009215:Myometrium / Q000187:drug effects / Q000378:metabolism*; D036801:Parturition / Q000502:physiology*; D011247:Pregnancy; D011273:Pregnancy, Prolonged / Q000378:metabolism*; D034741:RNA, Small Interfering; D011980:Receptors, Progesterone / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
chemical_list: D006727:Hormone Antagonists; C489676:KLF9 protein, human; D051741:Kruppel-Like Transcription Factors; D034741:RNA, Small Interfering; D011980:Receptors, Progesterone; D015735:Mifepristone