The developmental origins of health and diseases (DOHaD) is a concept stating that adverse intrauterine environments contribute to the health risks of offspring. Since the theory emerged more than 30 years ago, many epidemiological and animal studies have confirmed that in utero exposure to environmental insults, including hyperglycemia and chemicals, increased the risk of developing noncommunicable diseases (NCDs). These NCDs include metabolic syndrome, type 2 diabetes, and complications such as diabetic cardiomyopathy. Studying the effects of different environmental insults on early embryo development would aid in understanding the underlying mechanisms by which these insults promote NCD development. Embryonic stem cells (ESCs) have also been utilized by researchers to study the DOHaD. ESCs have pluripotent characteristics and can be differentiated into almost every cell lineage; therefore, they are excellent in vitro models for studying early developmental events. More importantly, human ESCs (hESCs) are the best alternative to human embryos for research because of ethical concerns. In this review, we will discuss different maternal conditions associated with DOHaD, focusing on the complications of maternal diabetes. Next, we will review the differentiation protocols developed to generate different cell lineages from hESCs. Additionally, we will review how hESCs are utilized as a model for research into the DOHaD. The effects of environmental insults on hESC differentiation and the possible involvement of epigenetic regulation will be discussed.

中文翻译：

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人类胚胎干细胞作为研究2型糖尿病发展起源的体外模型。

健康与疾病的发展起源（DOHaD）是一个概念，指出子宫内不利的环境会影响后代的健康风险。由于理论超过30年前出现的，许多流行病学和动物研究已经证实，在子宫内暴露于包括高血糖和化学物质在内的环境损害，会增加患非传染性疾病（NCDs）的风险。这些非传染性疾病包括代谢综合征，2型糖尿病和糖尿病性心肌病等并发症。研究不同的环境侮辱对早期胚胎发育的影响将有助于理解这些侮辱促进NCD发育的潜在机制。研究人员还利用胚胎干细胞（ESC）来研究DOHaD。ESC具有多能性特征，可以分化为几乎每个细胞谱系。因此，它们在体外非常好研究早期发展事件的模型。更重要的是，出于道德考虑，人类胚胎干细胞（hESC）是人类胚胎研究的最佳替代品。在这篇综述中，我们将讨论与DOHaD相关的不同孕产妇状况，重点是孕产妇糖尿病的并发症。接下来，我们将回顾为从hESC产生不同细胞谱系而开发的分化方案。此外，我们将回顾如何将hESCs用作DOHaD研究的模型。将讨论环境侮辱对hESC分化的影响以及表观遗传调控的可能参与。