Department of Woman, Mother and Neonate, 'V. Buzzi' Children Hospital, ASST Fatebenefratelli Sacco, 20141 Milan, Italy.
Department of Biomedical and Clinical Sciences, "Luigi Sacco", University of Milan, 20157 Milan, Italy.
Int J Mol Sci. 2021 Feb 9;22(4):1732. doi: 10.3390/ijms22041732.
Overweight and obesity during pregnancy have been associated with increased birth weight, childhood obesity, and noncommunicable diseases in the offspring, leading to a vicious transgenerational perpetuating of metabolic derangements. Key components in intrauterine developmental programming still remain to be identified. Obesity involves chronic low-grade systemic inflammation that, in addition to physiological adaptations to pregnancy, may potentially expand to the placental interface and lead to intrauterine derangements with a threshold effect. Animal models, where maternal inflammation is mimicked by single injections with lipopolysaccharide (LPS) resembling the obesity-induced immune profile, showed increased adiposity and impaired metabolic homeostasis in the offspring, similar to the phenotype observed after exposure to maternal obesity. Cytokine levels might be specifically important for the metabolic imprinting, as cytokines are transferable from maternal to fetal circulation and have the capability to modulate placental nutrient transfer. Maternal inflammation may induce metabolic reprogramming at several levels, starting from the periconceptional period with effects on the oocyte going through early stages of embryonic and placental development. Given the potential to reduce inflammation through inexpensive, widely available therapies, examinations of the impact of chronic inflammation on reproductive and pregnancy outcomes, as well as preventive interventions, are now needed.
怀孕期间超重和肥胖与出生体重增加、儿童肥胖和后代的非传染性疾病有关,导致代谢紊乱在代际间持续存在。宫内发育编程的关键组成部分仍有待确定。肥胖涉及慢性低度全身炎症,除了对妊娠的生理适应外,炎症可能扩展到胎盘界面,并导致宫内紊乱,达到阈值效应。动物模型中,通过单次注射类似于肥胖诱导的免疫特征的脂多糖 (LPS) 模拟母体炎症,显示后代的脂肪量增加和代谢稳态受损,类似于暴露于母体肥胖后观察到的表型。细胞因子水平对于代谢印迹可能特别重要,因为细胞因子可从母体转移到胎儿循环,并具有调节胎盘营养转移的能力。母体炎症可能在几个层面上诱导代谢重编程,从受孕前时期开始,对卵子通过胚胎和胎盘发育的早期阶段产生影响。鉴于通过廉价、广泛可用的治疗方法减少炎症的潜力,现在需要检查慢性炎症对生殖和妊娠结局的影响以及预防干预措施。