Reversal of maternal obesity attenuates hypoxia and improves placental development in the preeclamptic-like BPH/5 mouse model.

IF 0.8 4区 生物学 Q4 BIOLOGY
Daniella M Adams, Kalie F Beckers, Juliet P Flanagan, Viviane C L Gomes, Chin-Chi Liu, Jenny L Sones
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Abstract

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 Hif1α and 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.

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在先兆子痫样BPH/5小鼠模型中,逆转母体肥胖可减轻缺氧并改善胎盘发育。
背景:肥胖女性有更高的不良妊娠结局风险,包括先兆子痫(PE)。妊娠晚期高血压、异常胎儿胎盘发育和胎儿生长受限(FGR)是PE的标志,在BPH/5小鼠中自发观察到。与肥胖的先兆子痫女性相似,BPH/5小鼠的内脏白色脂肪组织(WAT)和循环瘦素含量较高。我们假设,在妊娠期BPH/5小鼠中,母体肥胖和血清瘦素的减少将通过降低缺氧标志物和母体-胎儿界面瘦素的表达来改善胎儿胎盘的发育。方法:为了验证这一假设,从胚胎第(e)0.5天开始,将BPH/5小鼠随意喂食(lib)和成对喂食(PF)给C57随意喂食对照。在e7.5植入位点评估缺氧相关基因、缺氧诱导因子(Hif)1α、干细胞因子(Scf)、血红素加氧酶-1(Ho-1)、瘦素(Lep)和瘦素受体(LepR)。结果:与PF减弱的C57相比,BPH/5 ad-lib的Hif1α、Scf和Ho-1mRNA增加了1.5至2倍,瘦素mRNA增加了3倍以上。外源性瘦素促进了体外e7.5蜕膜中Hif1α和Ho-1mrna的表达。缺氧条件下蜕膜瘦素mRNA表达无明显变化。此外,BPH/5 PF小鼠在妊娠后期表现出改善的胎儿和胎盘结果,e18.5增加了胎盘血管面积,FGR减弱。结论:总之,在该模型中,从受孕开始成对喂养BPH/5小鼠可以通过降低瘦素和缺氧相关标志物来改善胎盘血管系统的形成。未来的研究需要更好地确定缺氧和瘦素对肥胖孕妇妊娠结局的影响。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Biocell
Biocell 生物-生物学
CiteScore
1.50
自引率
16.70%
发文量
259
审稿时长
>12 weeks
期刊介绍: BIOCELL welcomes Research articles and Review papers on structure, function and macromolecular organization of cells and cell components, focusing on cellular dynamics, motility and differentiation, particularly if related to cellular biochemistry, molecular biology, immunology, neurobiology, and on the suborganismal and organismal aspects of Vertebrate Reproduction and Development, Invertebrate Biology and Plant Biology.
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