Sorbonne-Paris-Cité, Laboratoire B2PE (Biologie et Pathologie du Pancréas Endocrine), Unité BFA (Biologie Fonctionnelle et Adaptative), Université Paris-Diderot, CNRS UMR 8251, F-75205 Paris CEDEX 13, France.
Inserm U1065 C3M, Team Control of Gene Expression (10), Université Côte d'Azur, 151 Route de Ginestière, 06204 Nice CEDEX 3, France.
Nutrients. 2019 Jan 22;11(2):233. doi: 10.3390/nu11020233.
Extensive epidemiological and experimental evidence have shown that exposure to an adverse intrauterine environment as observed in offspring of pregnancies complicated by obesity or diabetes, can program susceptibility to metabolic, endocrine and cardiovascular disorders later in life. Although most studies have concentrated on the maternal environment, it is also becoming evident that paternal exposure to obesity or diabetes can result in the later development of metabolic disorders in the offspring. Such programmed effects might not be limited to the first directly exposed generation, but could be transmitted to subsequent generations. This suggests the existence of mechanisms by which metabolic changes in parental phenotype are transmissible to offspring. The mechanisms which underpin the transmission of the programmed effects across generations are still unclear. However, epigenetic regulation of transcription has emerged as a strong candidate for mediating the heritability of metabolic diseases. Here, we review the most relevant evidence from human and animal studies showing transmission of programming effects of obesity or diabetes across generations, and the current mechanisms underlying either maternal or paternal influences on the metabolic status of offspring.
大量的流行病学和实验证据表明,在肥胖或糖尿病孕妇所生育的后代中观察到的不良宫内环境暴露,可导致后代在以后的生活中易患代谢、内分泌和心血管疾病。尽管大多数研究都集中在母体环境上,但越来越明显的是,父体暴露于肥胖或糖尿病也会导致后代代谢紊乱的发生。这种编程效应可能不仅局限于第一代直接暴露的个体,还可能传递给后代。这表明存在代谢变化的父母表型可传递给后代的机制。然而,尚不清楚跨代传递编程效应的机制。然而,转录的表观遗传调控已成为介导代谢疾病遗传性的有力候选者。在这里,我们综述了来自人类和动物研究的最相关证据,这些证据表明肥胖或糖尿病的编程效应可在代际间传递,以及母系或父系对后代代谢状态影响的当前机制。