Dyslipidemia and the role of adipose tissue in early pregnancy in the BPH/5 mouse model for preeclampsia
Dyslipidemia and the role of adipose tissue in early pregnancy in the BPH/5 mouse model for preeclampsia
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DOI：
10.1152/ajpregu.00334.2018
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发表时间：
2019-07-01
影响因子：
2.8
通讯作者：
Sones, Jenny L.
中科院分区：
文献类型：
--
作者：
Reijnders, Dorien;Olson, Kelsey N.;Sones, Jenny L.
妊娠期高血压疾病先兆子痫（PE）是胎儿和母亲发病/死亡的主要原因。肥胖会增加患PE的风险。推测是通过从脂肪组织释放炎性介质，但确切的病因仍然很大程度上未知。使用肥胖PE样血压高崇高5（BPH/5）和瘦胎龄匹配的C57 B16小鼠，我们的目的是获得洞察差异生殖白色脂肪组织（rWAT）基因表达。循环脂质和炎症的母胎界面在怀孕早期。此外，我们研究了妊娠早期7天25%热量限制（CR）对rWAT和着床部位基因表达的影响。与C57 B16相比，雌性BPH/5在妊娠前是血脂异常的，并且在整个妊娠期间显示rWAT质量、循环胆固醇、游离脂肪酸和三酰甘油水平的放大。RNA测序显示，怀孕的BPII/5小鼠在胚胎第7.5天在与炎症和胆固醇生物合成相关的途径中具有升高的基因富集。胆固醇相关的HMGCS 1，MVD，Cyp 51 a1和DHCR的表达通过定量逆转录聚合酶链反应进行验证。在妊娠的前7天，CR将这些基因的相对mRNA表达恢复到与C57 B16妊娠雌性相当的水平，并在e7.5时降低BPH/5小鼠中rWAT和着床部位的循环瘦素和促炎性前列腺素合酶2的表达。我们的数据表明，rWAT在血脂异常状态和炎症性子宫环境中可能发挥作用，这可能是PE发病机制的基础。未来的研究应进一步探讨脂肪组织的生理功能与PE相关妊娠结局的关系。
The hypertensive pregnancy disorder preeclampsia (PE) is a leading cause of fetal and maternal morbidity/mortality. Obesity increases the risk to develop PE. presumably via the release of inflammatory mediators from the adipose tissue, but the exact etiology remains largely unknown. Using obese PE-like blood pressure high sublime 5 (BPH/5) and lean gestational age-matched C57B16 mice, we aimed to obtain insight into differential reproductive white adipose tissue (rWAT) gene expression. circulating lipids and inflammation at the maternalfetal interface during early pregnancy. In addition, we investigated the effect of 7 days 25% calorie restriction (CR) in early pregnancy on gene expression in rWAT and implantation sites. Compared with C57B16, female BPH/5 are dyslipidemic before pregnancy and show an amplification of rWAT mass, circulating cholesterol, free fatty acids, and triacylglycerol levels throughout pregnancy. RNA sequencing showed that pregnant BPII/5 mice have elevated gene enrichment in pathways related to inflammation and cholesterol biosynthesis at embryonic day (e) 7.5. Expression of cholesterol-related HMGCS1, MVD, Cyp51a1, and DHCR was validated by quantitative reverse-transcription-polymerase chain reaction. CR during the first 7 days of pregnancy restored the relative mRNA expression of these genes to a level comparable to C57B16 pregnant females and reduced the expression of circulating leptin and proinflammatory prostaglandin synthase 2 in both rWAT and implantation sites in BPH/5 mice at e7.5. Our data suggest a possible role for rWAT in the dyslipidemic state and inflammatory uterine milieu that might underlie the pathogenesis of PE. Future studies should further address the physiological functioning of the adipose tissue in relation to PE-related pregnancy outcomes.