Institute for Fetology, The First Affiliated Hospital of Soochow University, Suzhou 215006, China.
Department of Obstetrics and Gynecology, Suzhou Dushu Lake Hospital, Clinical College of Soochow University, Suzhou 215006, China.
Cells. 2022 Nov 2;11(21):3474. doi: 10.3390/cells11213474.
The fetal origins of adult disease (FOAD) hypothesis holds that events during early development have a profound impact on one's risk for the development of future adult disease. Studies from humans and animals have demonstrated that many diseases can begin in childhood and are caused by a variety of early life traumas, including maternal malnutrition, maternal disease conditions, lifestyle changes, exposure to toxins/chemicals, improper medication during pregnancy, and so on. Recently, the roles of Peroxisome proliferator-activated receptors (PPARs) in FOAD have been increasingly appreciated due to their wide variety of biological actions. PPARs are members of the nuclear hormone receptor subfamily, consisting of three distinct subtypes: PPARα, β/δ, and γ, highly expressed in the reproductive tissues. By controlling the maturation of the oocyte, ovulation, implantation of the embryo, development of the placenta, and male fertility, the PPARs play a crucial role in the transition from embryo to fetus in developing mammals. Exposure to adverse events in early life exerts a profound influence on the methylation pattern of PPARs in offspring organs, which can affect development and health throughout the life course, and even across generations. In this review, we summarize the latest research on PPARs in the area of FOAD, highlight the important role of PPARs in FOAD, and provide a potential strategy for early prevention of FOAD.
成人疾病的胎儿起源（FOAD）假说认为，早期发育过程中的事件对一个人未来患成人疾病的风险有深远影响。来自人类和动物的研究表明，许多疾病可以在儿童时期开始，并由各种早期生活创伤引起，包括母体营养不良、母体疾病状况、生活方式改变、暴露于毒素/化学物质、怀孕期间不当用药等。最近，由于其广泛的生物学作用，过氧化物酶体增殖物激活受体（PPARs）在 FOAD 中的作用越来越受到重视。PPARs 是核激素受体亚家族的成员，由三个不同的亚型组成：PPARα、β/δ 和 γ，在生殖组织中高度表达。通过控制卵母细胞的成熟、排卵、胚胎着床、胎盘发育和男性生育能力，PPARs 在发育中的哺乳动物从胚胎向胎儿的过渡中起着至关重要的作用。在生命早期接触到不良事件会对后代器官中 PPARs 的甲基化模式产生深远影响，这可能会影响整个生命过程中的发育和健康，甚至会跨代影响。在这篇综述中，我们总结了 PPARs 在 FOAD 领域的最新研究，强调了 PPARs 在 FOAD 中的重要作用，并为 FOAD 的早期预防提供了一种潜在策略。
