Background:Women with obesity have higher risk of adverse pregnancy outcomes,including preeclampsia(PE).Late-gestational hypertension,aberrant fetoplacental development,and fetal growth restriction(FGR),hallmarks of P...Background:Women with obesity have higher risk of adverse pregnancy outcomes,including preeclampsia(PE).Late-gestational hypertension,aberrant fetoplacental development,and fetal growth restriction(FGR),hallmarks of PE,are observed spontaneously in BPH/5 mice.Similar to obese preeclamptic women,BPH/5 mice have higher visceral white adipose tissue(WAT)and circulating leptin.We hypothesized that attenuation of maternal obesity and serum leptin in pregnant BPH/5 mice will improve fetoplacental development by decreasing hypoxia markers and leptin expression at the maternal-fetal interface.Methods:To test this hypothesis,BPH/5 mice were fed ad libitum(lib)and pair-fed(PF)to C57 ad lib controls beginning at embryonic day(e)0.5.Hypoxia-related genes,hypoxia inducible factor(Hif)1α,stem cell factor(Scf),heme oxygenase-1(Ho-1),leptin(Lep),and leptin receptor(LepR)were assessed in e7.5 implantation sites.Results:BPH/5 ad lib had 1.5 to 2-fold increase in Hif1α,Scf,and Ho-1 mRNA and a greater than 3-fold increase in leptin mRNA vs.C57 that was attenuated with PF.Exogenous leptin promoted Hif1αand Ho-1 mRNA expression in e7.5 decidua in vitro.While hypoxic conditions in vitro did not change decidual leptin mRNA.Furthermore,BPH/5 PF mice demonstrated improved fetal and placental outcomes later in gestation,with greater placental vascular area by e18.5 and attenuation of FGR.Conclusion:In conclusion,pair-feeding BPH/5 mice beginning at conception may improve placental vasculature formation via decreased leptin and hypoxia-associated markers in this model.Future investigations are needed to better determine the effect of hypoxia and leptin on pregnancy outcomes in obese pregnant women.展开更多
文摘Background:Women with obesity have higher risk of adverse pregnancy outcomes,including preeclampsia(PE).Late-gestational hypertension,aberrant fetoplacental development,and fetal growth restriction(FGR),hallmarks of PE,are observed spontaneously in BPH/5 mice.Similar to obese preeclamptic women,BPH/5 mice have higher visceral white adipose tissue(WAT)and circulating leptin.We hypothesized that attenuation of maternal obesity and serum leptin in pregnant BPH/5 mice will improve fetoplacental development by decreasing hypoxia markers and leptin expression at the maternal-fetal interface.Methods:To test this hypothesis,BPH/5 mice were fed ad libitum(lib)and pair-fed(PF)to C57 ad lib controls beginning at embryonic day(e)0.5.Hypoxia-related genes,hypoxia inducible factor(Hif)1α,stem cell factor(Scf),heme oxygenase-1(Ho-1),leptin(Lep),and leptin receptor(LepR)were assessed in e7.5 implantation sites.Results:BPH/5 ad lib had 1.5 to 2-fold increase in Hif1α,Scf,and Ho-1 mRNA and a greater than 3-fold increase in leptin mRNA vs.C57 that was attenuated with PF.Exogenous leptin promoted Hif1αand Ho-1 mRNA expression in e7.5 decidua in vitro.While hypoxic conditions in vitro did not change decidual leptin mRNA.Furthermore,BPH/5 PF mice demonstrated improved fetal and placental outcomes later in gestation,with greater placental vascular area by e18.5 and attenuation of FGR.Conclusion:In conclusion,pair-feeding BPH/5 mice beginning at conception may improve placental vasculature formation via decreased leptin and hypoxia-associated markers in this model.Future investigations are needed to better determine the effect of hypoxia and leptin on pregnancy outcomes in obese pregnant women.
