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Abstract
Epidemiological evidence has shown an association between prenatal malnutrition and a higher risk of developing metabolic disease in adult life. An inadequate intrauterine milieu affects both growth and development, leading to a permanent programming of endocrine and metabolic functions. Programming may be due to the epigenetic modification of genes implicated in the regulation of key metabolic mechanisms, including DNA methylation, histone modifications, and microRNAs (miRNAs). The expression of miRNAs in organs that play a key role in metabolism is influenced by in utero programming, as demonstrated by both experimental and human studies. miRNAs modulate multiple pathways such as insulin signaling, immune responses, adipokine function, lipid metabolism, and food intake. Liver is one of the main target organs of programming, undergoing structural, functional, and epigenetic changes following the exposure to a suboptimal intrauterine environment. The focus of this review is to provide an overview of the effects of exposure to an adverse in utero milieu on epigenome with a focus on the molecular mechanisms involved in liver programming.
Highlights
Life events are associated with susceptibility to chronic diseases in adult life (Gluckman et al, 2005)
Several studies have shown a clear link between the exposure to a suboptimal in utero environment leading to intrauterine growth retardation (IUGR) and the development of cardiometabolic disease in adulthood (Barker and Osmond, 1986; Barker et al, 1989)
We investigated the effects induced by an adverse intrauterine environment, using an animal model (Sprague-Dawley rats) of intrauterine growth restriction obtained through maternal uterine artery ligation on day 19 of gestation (Puglianiello et al, 2007; Germani et al, 2008; Puglianiello et al, 2009; Deodati et al, 2018)
Summary
An inadequate intrauterine milieu affects both growth and development, leading to a permanent programming of endocrine and metabolic functions. Programming may be due to the epigenetic modification of genes implicated in the regulation of key metabolic mechanisms, including DNA methylation, histone modifications, and microRNAs (miRNAs). The expression of miRNAs in organs that play a key role in metabolism is influenced by in utero programming, as demonstrated by both experimental and human studies. Liver is one of the main target organs of programming, undergoing structural, functional, and epigenetic changes following the exposure to a suboptimal intrauterine environment. The focus of this review is to provide an overview of the effects of exposure to an adverse in utero milieu on epigenome with a focus on the molecular mechanisms involved in liver programming
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