Complement in reproductive white adipose tissue characterizes the obese preeclamptic-like BPH/5 mouse prior to and during pregnancy

© 2020 by the authors. Licensee MDPI, Basel, Switzerland. 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 visceralWAT adjacent to the female reproductive tract (reproductiveWAT) 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 reproductiveWAT 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 e_ect of calorie restriction on C3 throughout pregnancy and the role of maternal obesity in PE

An Overview of Obesity, Cholesterol, and Systemic Inflammation in Preeclampsia

Preeclampsia (PE), an inflammatory state during pregnancy, is a significant cause of maternal and fetal morbidity and mortality. Adverse outcomes associated with PE include hypertension, proteinuria, uterine/placental abnormalities, fetal growth restriction, and pre-term birth. Women with obesity have an increased risk of developing PE likely due to impaired placental development from altered metabolic homeostasis. Inflammatory cytokines from maternal adipose tissue and circulating cholesterol have been linked to systemic inflammation, hypertension, and other adverse outcomes associated with PE. This review will summarize the current knowledge on the role of nutrients, obesity, and cholesterol signaling in PE with an emphasis on findings from preclinical models

The BPH/5 Mouse Model of Superimposed Preeclampsia Is Not a Model of HELLP Syndrome

Preeclampsia (PE) is a multisystemic disease of pregnancy affecting 2–8% of women worldwide. PE-induced liver disease is a rare but important complication of pregnancy. The pathogenesis of liver dysfunction in PE is poorly understood, but is correlated with dysregulated angiogenic, inflammatory, and hypoxic events in the early phase of placental development. Because BPH/5 mice develop the maternal and fetal hallmarks of PE during pregnancy, we hypothesized that they may also share the clinicopathologic findings of the human PE-associated hemolysis elevated liver transaminases low platelets (HELLP) syndrome. Using this model, we determined that microangiopathic hemolysis, thrombocytopenia, and elevated liver enzymes do not occur in mid to late gestation. Pregnant BPH/5 mice do not develop histologic evidence of hepatic inflammation, but they do have increased microsteatosis scores at preconception and in mid to late gestation that progress to macrosteatosis in a subset of mice in late gestation. The transcriptional upregulation of TNF-α, CXCL-10, and TLR-2 occurs in mid gestation prior to the onset of macrosteatosis. The BPH/5 female mouse is not a model of HELLP syndrome, but may be a model of fatty liver disease associated with pregnancy