title: Intrauterine bacterial inoculation induces labor in the mouse by mechanisms other than progesterone withdrawal.
abstract: We tested the hypothesis that progesterone (P(4)) withdrawal is the primary mechanism by which intrauterine bacteria induce preterm labor in mice. CD-1 mice on Day 14.5 of a 19- to 20-day gestation were subjected to one of four treatments: 1) intrauterine injection of sterile medium, 2) intrauterine injection of 10(6) heat-killed Escherichia coli bacteria, 3) intrauterine injection of 10(9) heat-killed E. coli, or 4) ovariectomy. Mice were then killed at four time points from 0.75 to 11 h after surgery for serum collection. Separately, animals were pretreated either with s.c. P(4) or with vehicle 2 h before ovariectomy or high-dose bacterial inoculation. Ovariectomy led to a rapid fall in serum P(4) levels of 60% by 1 h and 81% by 8 h compared with levels in controls (P < 0.001). In contrast, intrauterine inoculation with 10(9) bacteria led to a more modest decline in P(4) of only 28% by 8 h (P = 0.24, which was no different from that of 10(6) bacteria, an inoculum below the threshold for preterm delivery). Despite significantly lower levels of P(4) in the ovariectomy group, time to delivery was significantly shorter with 10(9) bacteria intrauterine (24 +/- 5.6 h vs. 19 +/- 3.6 h, P = 0.03). Pretreatment with 1.5 mg P(4) per mouse prolonged the interval to delivery following both ovariectomy and high-dose bacteria, in association with pharmacologically elevated serum P(4) levels. In contrast, physiologic P(4) supplementation (0.375 mg/mouse) prolonged gestation only in the ovariectomy group. We conclude that withdrawal of endogenous P(4) is not the primary cause of labor following intrauterine bacterial inoculation in mice.
authors.affiliation: Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Evanston, Illinois 60201, USA. e-hirsch@northwestern.edu
authors.forename: Emmet
authors.initials: E
authors.lastname: Hirsch
authors.forename: Rebecca
authors.initials: R
authors.lastname: Muhle
mesh_terms: D000818:Animals; D004927:Escherichia coli Infections; D005260:Female; D005865:Gestational Age; D051379:Mice; D007752:Obstetric Labor, Premature / Q000382:microbiology*; D010052:Ovariectomy; D011247:Pregnancy; D011374:Progesterone / Q000008:administration & dosage* / Q000097:blood / Q000502:physiology; D014599:Uterus / Q000382:microbiology*
chemical_list: D011374:Progesterone