Complement in Reproductive White Adipose Tissue Characterizes the Obese Preeclamptic-Like BPH/5 Mouse Prior to and During Pregnancy

SIMPLE SUMMARY: Preeclampsia is a life-threatening disorder that occurs in 10% of pregnant women worldwide. It presents as high blood pressure and multi-organ damage that when left untreated can result in death to both mother and baby. Treatment involves delivery of the placenta as well as the baby, often prematurely. Unfortunately, the cause of preeclampsia is unknown. However, there are known risk factors in women that may contribute to preeclampsia, including obesity. Increased adipose tissue (fat) has the potential to promote inflammation during pregnancy, which may negatively impact development of the baby and placenta, and lead to preeclampsia. This study aimed to show that reversal of maternal obesity through diet lowers inflammation in the fat and improves placental development, both of which have been shown to be necessary for pregnancy success. Utilizing obese female mice that demonstrate signs of preeclampsia (BPH/5), we showed that calorie restriction lowered inflammatory immune factors (complement) in the fat and restored essential growth factors in the developing placenta. In conclusion, these data suggest that targeting maternal obesity using calorie restriction and weight loss may improve pregnancy outcomes. Further studies are necessary to determine the influence of fat reduction in women and their likelihood of developing preeclampsia. ABSTRACT: Preeclampsia (PE) is a serious hypertensive disorder of pregnancy characterized by abnormal placental development with an unknown etiology. To better understand which women will develop PE, a number of maternal risk factors have been identified, including obesity. Visceral white adipose tissue (WAT) contains inflammatory mediators that may contribute to PE. To explore this, we utilized the blood pressure high (BPH)/5 mouse model of superimposed PE that spontaneously recapitulates the maternal PE syndrome. We hypothesized that BPH/5 visceral WAT adjacent to the female reproductive tract (reproductive WAT) is a source of complement factors that contribute to the inflammatory milieu and angiogenic imbalance at the maternal–fetal interface in this model and in preeclamptic women. To test our hypothesis, we calorie-restricted BPH/5 females for two weeks prior to pregnancy and the first seven days of pregnancy, which attenuated complement component 3 (C3) but not complement factor B, nor complement factor D, (adipsin) in the reproductive WAT or the implantation site in BPH/5. Furthermore, calorie restriction during pregnancy restored vascular endothelial and placental growth factor mRNA levels in the BPH/5 implantation site. These data show maternal reproductive WAT may be a source of increased C3 during pregnancy, which is increased at the maternal–fetal interface in preeclamptic BPH/5 mice. It also suggests that calorie restriction could regulate inflammatory mediators thought to contribute to placental dysfunction in PE. Future studies are necessary to examine the effect of calorie restriction on C3 throughout pregnancy and the role of maternal obesity in PE.