Intra-amniotic administration of lipopolysaccharide induces spontaneous preterm labor and birth in the absence of a body temperature change.

OBJECTIVE: Intra-amniotic infection is associated with spontaneous preterm labor. In most cases, the infection is subclinical and bacteria are detected in the amniotic cavity rather than in the chorioamniotic membranes. The aims of this study were to establish a model of intra-amniotic lipopolysaccharide (LPS)-induced preterm labor/birth that resembles the subclinical syndrome and to compare this model to two established models of LPS-induced preterm labor/birth. METHODS: Pregnant B6 mice received an intra-amniotic, intra-uterine, or intra-peritoneal injection of LPS (100 ng/amniotic sac, 15 µg/25 µL, and 15 µg/200 µL respectively) or PBS (control). Following injection, body temperature (every two hours for a 12-h period), gestational age, and the rate of preterm labor/birth were recorded. RESULTS: An intra-amniotic injection of LPS resulted in preterm labor/birth [LPS 80 ± 24.79% (8/10) versus PBS 0% (0/8); p = 0.001] without causing maternal hypothermia. Intra-peritoneal [LPS 100% (8/8) versus PBS 0% (0/8); p < 0.001)] and intra-uterine [LPS 100% (8/8) versus PBS 28.57 ± 33.47% (2/7); p =0 .007] injections of LPS induced preterm labor/birth; yet, maternal hypothermia was observed. CONCLUSION: Intra-amniotic injection of LPS induces preterm labor/birth in the absence of a body temperature change, which resembles the subclinical syndrome.

Human Chorionic Gonadotropin Has Anti-Inflammatory Effects at the Maternal-Fetal Interface and Prevents Endotoxin-Induced Preterm Birth, but Causes Dystocia and Fetal Compromise in Mice.

Human chorionic gonadotropin (hCG) is implicated in the maintenance of uterine quiescence by down-regulating myometrial gap junctions during pregnancy, and it was considered as a strategy to prevent preterm birth after the occurrence of preterm labor. However, the effect of hCG on innate and adaptive immune cells implicated in parturition is poorly understood. Herein, we investigated the immune effects of hCG at the maternal-fetal interface during late gestation, and whether this hormone can safely prevent endotoxin-induced preterm birth. Using immunophenotyping, we demonstrated that hCG has immune effects at the maternal-fetal interface (decidual tissues) by: 1) increasing the proportion of regulatory T cells; 2) reducing the proportion of macrophages and neutrophils; 3) inducing an M1 → M2 macrophage polarization; and 4) increasing the proportion of T helper 17 cells. Next, ELISAs were used to determine whether the local immune changes were associated with systemic concentrations of progesterone, estradiol, and/or cytokines (IFNgamma, IL1beta, IL2, IL4, IL5, IL6, IL10, IL12p70, KC/GRO, and TNFalpha). Plasma concentrations of IL1beta, but not progesterone, estradiol, or any other cytokine, were increased following hCG administration. Pretreatment with hCG prevented endotoxin-induced preterm birth by 44%, proving the effectiveness of this hormone as an anti-inflammatory agent. However, hCG administration alone caused dystocia and fetal compromise, as proven by Doppler ultrasound. These results provide insight into the mechanisms whereby hCG induces an anti-inflammatory microenvironment at the maternal-fetal interface during late gestation, and demonstrate its effectiveness in preventing preterm labor/birth. However, the deleterious effects of this hormone on mothers and fetuses warrant caution.