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a Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Evanston, Illinois 60201
b Department of Obstetrics and Gynecology, Columbia University College of Physicians & Surgeons, New York, New York 10032
We tested the hypothesis that progesterone (P4) 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 106 heat-killed Escherichia coli bacteria, 3) intrauterine injection of 109 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. P4 or with vehicle 2 h before ovariectomy or high-dose bacterial inoculation. Ovariectomy led to a rapid fall in serum P4 levels of 60% by 1 h and 81% by 8 h compared with levels in controls (P < 0.001). In contrast, intrauterine inoculation with 109 bacteria led to a more modest decline in P4 of only 28% by 8 h (P = 0.24, which was no different from that of 106 bacteria, an inoculum below the threshold for preterm delivery). Despite significantly lower levels of P4 in the ovariectomy group, time to delivery was significantly shorter with 109 bacteria intrauterine (24 ± 5.6 h vs. 19 ± 3.6 h, P = 0.03). Pretreatment with 1.5 mg P4 per mouse prolonged the interval to delivery following both ovariectomy and high-dose bacteria, in association with pharmacologically elevated serum P4 levels. In contrast, physiologic P4 supplementation (0.375 mg/mouse) prolonged gestation only in the ovariectomy group. We conclude that withdrawal of endogenous P4 is not the primary cause of labor following intrauterine bacterial inoculation in mice.
2 Correspondence: Emmet Hirsch, Department of Obstetrics and Gynecology, Evanston Northwestern Healthcare, 2650 Ridge Ave., Evanston, IL 60201. FAX: 847 773 5083; e-hirsch{at}northwestern.edu
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