Sarr Ousseynou, Rajagopaul Akasham, Zhao Shuang, Wang Xiaohang, Grynspan David, Eastabrook Genevieve, Li Liang, Regnault Timothy R H, de Vrijer Barbra
Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, London, ON N6A 5C1, Canada.
The Metabolomics Innovation Centre (TMIC), University of Alberta, Edmonton, AB T6G 2G2, Canada.
Biomedicines. 2025 Sep 3;13(9):2149. doi: 10.3390/biomedicines13092149.
Individuals with metabolically healthy obesity (MHO) and metabolically unhealthy obesity (MUO) in pregnancy are two distinct cardiometabolic populations, each potentially necessitating alternative clinical management. However, our understanding of the unique physiological effects of uncomplicated MHO on fetoplacental growth and metabolism remains limited. In this study, we aimed to identify changes in placental morphology and metabolites associated with maternal obesity, independent of pregnancy-related cardiometabolic complications. Placentae from women with a prepregnancy body mass index (BMI) < 25 kg/m (control; = 15) and women with MHO (prepregnancy BMI > 30 kg/m with no cardiometabolic diseases; = 15) were analyzed for indices of placental growth and untargeted metabolomics. Complementary assessments were conducted on proinflammatory genes and antioxidant defense system genes, proteins, and enzymes, along with lipid peroxidation markers. Clear placentomegaly without histopathological changes was observed in uncomplicated MHO pregnancies. The metabolite 3-aminoisobutanoic acid emerged as the top-ranked feature distinguishing placentae from MHO individuals from control placentae, and changes in the cysteine, methionine, and vitamin B6 metabolism pathways were among the most distinct differences identified. These findings illustrate an altered placental morphology and metabolomic profile specific to uncomplicated MHO, offering new insights into how obesity, without cardiometabolic complications, may influence fetoplacental growth and metabolism. They may also represent a crucial first step towards marker identification for MHO pregnancy and underscore the importance of alternative care pathways when obesity is present but metabolic comorbidities are absent.
孕期患有代谢健康型肥胖（MHO）和代谢不健康型肥胖（MUO）的个体是两个不同的心脏代谢群体，每一类群体可能都需要不同的临床管理方式。然而，我们对单纯性MHO对胎儿胎盘生长和代谢的独特生理影响的了解仍然有限。在本研究中，我们旨在确定与母体肥胖相关的胎盘形态和代谢物变化，而不考虑与妊娠相关的心脏代谢并发症。分析了孕前体重指数（BMI）<25kg/m²的女性（对照组；n = 15）和患有MHO的女性（孕前BMI>30kg/m²且无心脏代谢疾病；n = 15）的胎盘，以评估胎盘生长指标和非靶向代谢组学。对促炎基因和抗氧化防御系统基因、蛋白质和酶以及脂质过氧化标志物进行了补充评估。在单纯性MHO妊娠中观察到明显的胎盘肿大，但无组织病理学变化。代谢物3-氨基异丁酸是区分MHO个体胎盘与对照胎盘的最显著特征，半胱氨酸、蛋氨酸和维生素B6代谢途径的变化是所确定的最明显差异之一。这些发现说明了单纯性MHO特有的胎盘形态和代谢组学特征发生了改变，为无心脏代谢并发症的肥胖如何影响胎儿胎盘生长和代谢提供了新的见解。它们也可能是识别MHO妊娠标志物的关键第一步，并强调了在存在肥胖但无代谢合并症时采用替代护理途径的重要性。
