Inflammatory Reproductive White Adipose Tissue Characterizes The Obese Preeclamptic‐like BPH/5 Mouse prior to Pregnancy
Authors: Olson Kelsey , Reijnders‐Most Dorien , Douglas Nataki , Redman Leanne M. , Sones Jenny Liford 
Published: June 2021

BackgroundPreeclampsia (PE) is a serious hypertensive disorder of pregnancy characterized by abnormal placental development. Preeclamptic pregnancies are characterized by a heightened state of inflammation however, the etiology is unknown. A number of pre‐conception risk factors have been identified, including maternal obesity. Our laboratory studies the BPH/5 mouse that spontaneously develops PE features, including late‐gestational hypertension, placental defects, and inflammation at the maternal‐fetal interface. We recently showed that BPH/5 female mice are obese prior to pregnancy with increased WAT. Pre‐pregnancy visceral WAT (adjacent to the female reproductive tract), has upregulated expression of pro‐inflammatory cytokines when fed ad libitum. Interestingly, calorie restriction (CR) reduced body weight, reproductive WAT, and expression of pro‐inflammatory cytokines in BPH/5. We hypothesized that pre‐pregnancy reproductive WAT is a source of complement factors that contribute to the inflammatory milieu at the maternal‐fetal interface in BPH/5.MethodsTo test our hypothesis, we used qRT‐PCR to measure mRNA expression of complement factor 3 (C3), complement factor B (CfB), and complement factor D (adipsin) in the non‐pregnant reproductive WAT from female ad libitum fed C57BL/6 and BPH/5, and 14 day calorie restricted BPH/5 mice. Complement factor mRNA expression was also measured e7.5 implantation sites from ad libitum fed C57BL/6 and BPH/5, and 7 day calorie restricted BPH/5 mice.ResultsC3 was significantly upregulated in ad libitum fed BPH/5 non‐pregnant reproductive WAT compared to C57BL/6 (n=6, p<0.05). C3 was normalized after 14 days of CR in non‐pregnant BPH/5 compared to ad libitum fed BPH/5 mice (n=5, p<0.05). Cfb and adipsin mRNA levels were similar in ad libitum fed BPH/5 and C57BL/6 non‐pregnant reproductive WAT (n=6, p>0.05). C3 was significantly upregulated in ad libitum BPH/5 e7.5 implantation sites compared to C57BL/6 (n=6, p<0.05). C3 overexpression was blunted at the maternal‐fetal interface after 7 days of CR in pregnant BPH/5 compared to ad libitum fed BPH/5 mice (n=5, p<0.05).ConclusionComplement factor 3 levels are increased at the maternal‐fetal interface in pregnant BPH/5 mice. Our data suggest that pre‐pregnancy maternal reproductive WAT may be the source of C3 and that calorie restriction prior to obese pregnancy could have a considerable effect on the regulation of inflammatory factors thought to contribute to placental dysfunction in PE. Future studies examining the effect of calorie restriction on C3 deposition throughout pregnancy would be advantageous to understanding the role of obesity in the pathogenesis of PE.Support or Funding InformationThis work is supported by an LSU School of Veterinary Medicine (SVM) CORP grant.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.