关键词: Preeclampsia fatty acid esterification fatty acid oxidation fatty acid transport fetal sex gene expression mitochondria peroxisome placental lipid metabolism sexual dimorphism

来  源:   DOI:10.26502/ogr0159   PDF(Pubmed)

Abstract:
UNASSIGNED: Preeclampsia (PE) is a hypertensive disorder of pregnancy associated with adverse maternal and fetal outcomes. While placental dysfunction is implicated in PE pathogenesis, the impact of PE on placental lipid metabolism and its potential sexual dimorphism remains poorly understood.
UNASSIGNED: We conducted a comprehensive analysis of term placentas from PE and normotensive pregnancies with male and female fetuses. Lipid profiles were quantified using mass spectrometry, and mRNA expression of genes involved in fatty acid oxidation, esterification, and transport was assessed using qPCR.
UNASSIGNED: Placentas from PE pregnancies exhibited elevated lipid levels, with male placentas showing a more pronounced increase in triacylglycerols, cholesteryl esters, and free cholesterol compared to female placentas. Gene expression analysis revealed sexually dimorphic alterations, with male PE placentas exhibiting upregulation of genes involved in fatty acid uptake, oxidation, and esterification, while female PE placentas showed a more complex response with both upregulation and downregulation of certain genes. Notably, peroxisomal fatty acid oxidation was upregulated in male PE placentas but suppressed in female PE placentas.
UNASSIGNED: Our findings reveal sexually dimorphic alterations in placental lipid metabolism in PE, suggesting that male placentas may be more vulnerable to lipotoxicity. These insights may have implications for understanding the pathogenesis of PE and developing sex-specific interventions to improve maternal and fetal outcomes.
摘要:
先兆子痫(PE)是一种妊娠高血压疾病,与不良的母体和胎儿结局有关。虽然胎盘功能障碍与PE发病机制有关,PE对胎盘脂质代谢及其潜在的性二态性的影响仍然知之甚少。
我们对男性和女性胎儿的PE和正常血压妊娠的足月胎盘进行了综合分析。使用质谱对脂质进行定量,和参与脂肪酸氧化的基因的mRNA表达,酯化,并使用qPCR评估转运。
PE妊娠胎盘显示脂质水平升高,男性胎盘显示出三酰甘油更明显的增加,胆固醇酯,和游离胆固醇与女性胎盘相比。基因表达分析显示性二态改变,男性PE胎盘表现出与脂肪酸摄取有关的基因上调,氧化,和酯化,而女性PE胎盘显示出更复杂的反应,某些基因的上调和下调。值得注意的是,过氧化物酶体脂肪酸氧化在男性PE胎盘中上调,但在女性PE胎盘中被抑制。
我们的发现揭示了PE胎盘脂质代谢的性二态改变,这表明男性胎盘可能更容易受到脂毒性的影响。这些见解可能对理解PE的发病机制和开发性别特异性干预措施以改善母体和胎儿结局具有意义。
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