title: Maternal and fetal roles in bacterially induced preterm labor in the mouse.
abstract: BACKGROUND
  The relative roles of the mother and fetus in signaling for labor remain poorly understood.
  
  
  OBJECTIVE
  We previously demonstrated using gene knockout (KO) mice that Escherichia coli-induced preterm delivery is completely dependent on MyD88, a toll-like receptor adaptor protein. Here we leveraged this finding to conduct a genetic experiment testing whether the mother, the fetus, or both signal for parturition in bacterially induced labor.
  
  
  METHODS
  Six different maternal/fetal genotype combinations for MyD88 were studied: wild-type (WT) dams carrying one of the following: (1) WT or (2) MyD88 heterozygous (het) fetuses (generated by mating WT females with WT or MyD88-knockout [KO] males, respectively); (3) WT dams carrying MyD88-KO fetuses (generated by replacing the ovaries of WT females with MyD88-KO ovaries, followed by mating with MyD88-KO males); a similar strategy was used to generate MyD88-KO dams carrying (4) MyD88-KO, (5) MyD88 het, or (6) WT fetuses. On day 14.5 of gestation, mice received intrauterine injections of either 1 × 10(9) killed E coli or sterile medium. Delivery of ≥ 1 fetus within 48 hours was considered preterm. A separate group of similarly treated pregnant mice was euthanized 5 hours after surgery for gene expression and tissue analysis.
  
  
  RESULTS
  E coli-induced preterm delivery is dependent on maternal and not fetal genotype: > 95% of WT and < 5% of MyD88-KO dams deliver prematurely, regardless of fetal genotype (P = .0001). In contrast, fetal survival in utero is influenced by fetal genotype: in MyD88-KO dams, in which premature birth rarely occurs, only 81% of WT and 86% of MyD88-heterozygous fetuses were alive 48 hours after surgery compared with 100% of MyD88-KO fetuses (P < .01). Messenger ribonucleic acids for the inflammatory mediators interleukin-1β, tumor necrosis factor, interleukin-6, and cyclooxygenase-2 were elevated in uterine tissues only in WT mothers treated with E coli and were low or undetectable in the uteri of KO mothers or in animals treated with saline. Serum progesterone levels were lower in KO mothers with WT ovaries than in WT mothers with KO ovaries, but bacterial exposure did not have an impact on these levels.
  
  
  CONCLUSIONS
  In the murine E coli-induced labor model, preterm delivery and uterine expression of inflammatory mediators is determined by the mother and not the fetus and is not attributable to a decline in serum progesterone.
authors.affiliation: Departments of Obstetrics and Gynecology, NorthShore University HealthSystem, Evanston, IL.
authors.forename: Yana
authors.initials: Y
authors.lastname: Filipovich
authors.affiliation: Departments of Obstetrics and Gynecology, NorthShore University HealthSystem, Evanston, IL.
authors.forename: Jeremy
authors.initials: J
authors.lastname: Klein
authors.affiliation: Center for Biomedical Research Informatics, NorthShore University HealthSystem, Evanston, IL.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Departments of Obstetrics and Gynecology, NorthShore University HealthSystem, Evanston, IL. Electronic address: ehirsch@northshore.org.
authors.forename: Emmet
authors.initials: E
authors.lastname: Hirsch
mesh_terms: D000818:Animals; D051546:Cyclooxygenase 2 / Q000235:genetics; D004926:Escherichia coli; D004927:Escherichia coli Infections / Q000150:complications*; D005260:Female; D005313:Fetal Death; D005333:Fetus / Q000378:metabolism; D015870:Gene Expression; D006579:Heterozygote; D053583:Interleukin-1beta / Q000235:genetics; D015850:Interleukin-6 / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics* / Q000378:metabolism*; D007752:Obstetric Labor, Premature / Q000235:genetics* / Q000382:microbiology*; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000378:metabolism* / Q000382:microbiology; D047928:Premature Birth / Q000235:genetics; D011374:Progesterone / Q000097:blood; D012333:RNA, Messenger / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D014599:Uterus / Q000378:metabolism
chemical_list: D053583:Interleukin-1beta; D015850:Interleukin-6; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D011374:Progesterone; D051546:Cyclooxygenase 2
keywords: inflammation; mouse model; parturition; preterm labor