Abstract P224: Obesity Is Associated With Hypoxia At The Maternal-fetal Interface In A Mouse Model Of Superimposed Preeclampsia, BPH/5

Obesity impacts 1/3 of US adults. Maternal obesity significantly increases risk of adverse pregnancy outcomes, including preeclampsia (PE). Late-gestational hypertension and fetal growth restriction (FGR), hallmarks of PE, are observed spontaneously in BPH/5 mice. Similar to obese preeclamptic women, BPH/5 have increased visceral white adipose tissue (WAT) and are leptin resistant. We hypothesize that attenuation of maternal obesity and reduction of reproductive WAT in pregnant BPH/5 female mice will improve decidualization, placental development, and attenuate FGR. To test this hypothesis, pregnant C57 and BPH/5 female mice fed ad libitum (lib) and pair-fed (PF) BPH/5 female mice, beginning at day of copulatory plug detection, e0.5 (n=5/group), were utilized. Pair-feeding BPH/5 females the equivalent daily food intake of lean control ad lib fed C57 females reduced maternal WAT and circulating leptin in this model by e7.5 as well as reduced pro-inflammatory cytokines, Ptgs2 and IL-6, mRNA in the decidua. Therefore, we tested whether hypoxia-related genes, hypoxia inducible factor (Hif) 1α, heme oxygenase-1 (Ho-1), and stem cell factor (Scf), would be altered in the decidua of PF BPH/5 at e7.5. Using real time PCR, we found that e7.5 implantation sites from ad lib fed BPH/5 had a 1.5 to 2-fold increase in Hif1α, Ho-1, Scf, and VEGF mRNA (p<0.05) compared to C57 that was significantly reduced by PF. Furthermore, real time PCR for leptin (lep) mRNA showed a 6-fold increase in e7.5 implantation sites from ad lib fed BPH/5 versus C57 and lep along with lep receptor mRNA was reduced in PF BPH/5 (p<0.05). Therefore, PF BPH/5 pregnant mice have attenuated obesity and leptin in WAT, circulation, and e7.5 implantation sites that is associated with a reduction in markers of hypoxia at the maternal-fetal interface. Finally, BPH/5 PF litter sizes are significantly higher than ad lib fed, 6 vs 3.5, respectively (n=5-8; p<0.05) and symmetrical FGR is attenuated. In conclusion, maternal weight loss in BPH/5 beginning at conception may improve placental development by mitigating hypoxia at the maternal-fetal interface in this model. Future investigations are needed to determine this effect on the maternal hypertensive syndrome and offspring outcomes long-term.