201 Effect of mild restraint stress on lipopolysaccharide-induced preterm labor in murine model

Abstract

Prenatal stress leads to a pro-inflammatory state that may prime the immune system to respond aggressively to bacterial stimuli. This robust inflammatory response may be a mechanism for preterm delivery in individuals with high levels of chronic stress. The objective of this study was to assess the impact of antenatal stress on the responsivity of mice to lipopolysaccharide (LPS)-induced preterm labor. Nulliparous mice (n=39) underwent timed breeding at 8-10 weeks of age. Dams were then randomly assigned to either stress or control groups. The mice assigned to stress underwent daily 2-hour periods of restraint in a ventilated clear 50-mL conical centrifuge tube from E1-E15. On E15.5, mice from each group were randomly assigned to a 150-microliter intraperitoneal injection with either 15 micrograms LPS (E. coli O111:B4) or phosphate buffered saline (PBS). This low dose of LPS typically induces preterm labor in about 50% of mice. Mice were monitored in individual cages for the next 48 hours. The primary outcome was the number of dams exhibiting preterm labor (defined as bleeding or delivery of at least 1 fetus) within 48 hours. Mice were then sacrificed and uterine gross pathology inspected. Secondary outcomes were maternal death and presence of resorbed fetuses in the uteri. Outcomes were compared with Fisher’s Exact Test with a significant p-value of .05. In total, 10/10 of the mice exposed to antenatal stress and 7/12 of the control mice demonstrated preterm labor when exposed to low-dose LPS (Figure 1). Fisher’s Exact Test showed the rate of preterm labor after low-dose LPS injection was significantly higher in mice exposed to antenatal stress (p=.04). There were no maternal deaths observed. Two mice in the control-PBS group demonstrated resorbed fetuses. None of the other groups demonstrated resorbed fetuses (p=.52). Chronic mild restraint stress increases the sensitivity of mice to low-dose LPS-induced preterm labor. These data provide insight into a potential cause of increased preterm delivery rates among populations experiencing high rates of chronic stress.