The Roles Of Phosphodiesterase 4B(PDE4B)in LPS-induced Preterm Labor

Object:To investigate the roles of phosphodiesterase 4B (PDE4B) in myometrial inflammation and contraction of LPS-induced preterm labor (PTL), so as to provide some evidence for further understanding PTL pathogenesis and developing new tocolytic agent (PDE4B-selective inhibitor).Methods:We used Pde4b-/-(KO) female mice and their littermate wild type (WT) female mice to establish a PTL model in vivo. KO and WT female mice were mated with heterozygous male mice; on their Day 14 of gestations, the female mice were administrated either with LPS (400 μg/kg, i.p.) or with PBS (100 μl/10 g, i.p.) as sham controls, deviding the female mice into four groups:PBS-WT, PBS-KO, LPS-WT and LPS-KO. Gestation length of every maternal mice and the numbers of their survived or dead fetuses were recorded, and then the PTL rate and fetal motality rate of each group were calculated. Uterine tissues of maternal mice were harvested during there parturition and were then made into paraffin sections. Through HE staining and CD68-immunohistochemistry of these tissue sections, percentages of neutrophils and macrophages infiltrated in the myometria of each group were evaluated respectively.Results:After LPS stimulation, the PTL and fetal motality rates of WT mice were significantly increased (up to 85.7% and 84.4%, respectively). Neutrophils infiltrated in the myometria of LPS-WT group were also increased evidently, and the percentages of macrophages have the same tendency. Compared with LPS-WT group, the PTL and fetal motality rates of LPS-KO group were decreased significantly (14.3% and 55.3%, respectively); the percentage of neutrophils in the myometria of LPS-KO group was dramatically dropped, and macrophage invasion was also appeared to decline.Conclusion:In this study, we successfully established the animal model of preterm labor induced by LPS, and comfirmed the protective effect of PDE4B deletion against PTL and inflammation-induced fetal injury in vivo. Thereby, PDE4B may become a novel target for developing tocolytics. PDE4B contributes to leukocyte infiltration in the myometria of mice during labor, thus can be essential in inflammation progress; however, the exact role of PDE4B in LPS-induced myometrial contraction needs to be further explored.