NF-κB signaling pathway impairs fetal growth in mice by regulating recruitment of uterine trNK cells

Background　The nuclear factor kappa-B (NF-κB) pathway is involved in regulating the expression of chemokines, inflammatory cytokines and matrix metalloproteinases, and plays an important role in decidualization and embryo implantation. Objective　To investigate the effects of NF-κB activity on the growth of mouse and its possible mechanism.Methods　Thirty-two ICR mice were randomly divided into two groups, all of which underwent natural pregnancy. The experimental group received intraperitoneal injections of NF-KB inhibitor dissolved in PBS from gestational days 5.5 to 7.5, while the control group received intraperitoneal injections of the same volume of PBS during the same period. The conceptuses of the two groups were weighed at 8.5 days of gestation (n=10). On day 14.5 (n=6), the weight of offspring and placentas were weighed and placental efficiency (placenta weight/fetal weight) was calculated. Immunohistochemistry was used to detect the effect of NF-κB inhibitor on the number of trNK cells in the uterus of mice. Real time PCR was used to detect the expression of chemokines and cytokines related to NK cell recruitment and differentiation in the decidua. Results　NF- κB inhibitor administration significantly reduced the weights of implantation sites at gestation day 8.5 (P＜0.001), as well as fetal weight (P＜0.001), placental weight (P＜0.05), and placental efficiency (P＜0.01) at gestation day 14.5. At gestation day 8.5, APDC-treated mice exhibited a significantly reduced density of uterine trNK cells (proportion of immunopositive cells; P＜0.001). Furthermore, APDC treatment significantly decreased the expression levels of decidual chemokines and cytokines (P＜0.05). Conclusion　Inhibition of NF- κB activity can reduce the expression of chemokines and cytokines in the decidua of mice, and then affect the recruitment and differentiation of uterine trNK cells, resulting in growth restriction of offspring.