Mishra Jay S, Zhao Hanjie, Zheng Jing, Kumar Sathish
Department of Comparative Biosciences, School of Veterinary Medicine, University of Wisconsin, Madison, Wisconsin, United States of America.
Department of Obstetrics and Gynecology, School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin, United States of America.
Obstet Gynecol Res. 2024;7(3):49-58. doi: 10.26502/ogr0159. Epub 2024 Jul 23.
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.
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.
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.
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.
子痫前期（PE）是一种与孕产妇和胎儿不良结局相关的妊娠高血压疾病。虽然胎盘功能障碍与PE的发病机制有关，但PE对胎盘脂质代谢的影响及其潜在的性别差异仍知之甚少。
我们对患有PE的妊娠和血压正常的妊娠（胎儿为男性和女性）的足月胎盘进行了全面分析。使用质谱法定量脂质谱，并使用qPCR评估参与脂肪酸氧化、酯化和转运的基因的mRNA表达。
PE妊娠的胎盘脂质水平升高，与雌性胎盘相比，雄性胎盘的三酰甘油、胆固醇酯和游离胆固醇增加更为明显。基因表达分析揭示了性别差异改变，雄性PE胎盘表现出参与脂肪酸摄取、氧化和酯化的基因上调，而雌性PE胎盘对某些基因的上调和下调表现出更复杂的反应。值得注意的是，过氧化物酶体脂肪酸氧化在雄性PE胎盘中上调，但在雌性PE胎盘中受到抑制。
我们的研究结果揭示了PE中胎盘脂质代谢的性别差异改变，表明雄性胎盘可能更容易受到脂毒性的影响。这些见解可能有助于理解PE的发病机制，并制定针对性别的干预措施以改善孕产妇和胎儿结局。
