Epigenetics and life-long consequences of an adverse nutritional and diabetic intrauterine environment

Abstract

The phenomenon that adverse environmental exposures in early life are associated with increased susceptibilities for many adult, particularly metabolic diseases, is now referred to as ‘developmental origins of health and disease (DOHAD)’ or ‘Barker’ hypothesis. Fetal overnutrition and undernutrition have similar long-lasting effects on the setting of the neuroendocrine control systems, energy homeostasis, and metabolism, leading to life-long increased morbidity. There are sensitive time windows during early development, where environmental cues can program persistent epigenetic modifications which are generally assumed to mediate these gene–environment interactions. Most of our current knowledge on fetal programing comes from animal models and epidemiological studies in humans, in particular the Dutch famine birth cohort. In industrialized countries, there is more concern about adverse long-term consequences of fetal overnutrition, i.e. by exposure to gestational diabetes mellitus and/or maternal obesity which affect 10–20% of pregnancies. Epigenetic changes due to maternal diabetes/obesity may predispose the offspring to develop metabolic disease later in life and, thus, transmit the adverse environmental exposure to the next generation. This vicious cycle could contribute significantly to the worldwide metabolic disease epidemics. In this review article, we focus on the epigenetics of an adverse intrauterine environment, in particular gestational diabetes, and its implications for the prevention of complex disease.

Anti-Müllerian Hormone (AMH) and fertility management in agricultural species

“…Maternal nutritional status is considered a major cause of fetal developmental programming in humans, cattle and sheep (Gluckman & Hanson 2004, McMillen et al 2008, El Hajj et al 2014. We tested the hypothesis in cattle that dietary nutritional restriction (to 60% of maternal requirements) has permanent effects on the establishment of the ovarian reserve (total number of morphologically healthy follicles and oocytes) in offspring.…”

The Role of Malnutrition during Pregnancy and Its Effects on Brain and Skeletal Muscle Postnatal Development

“…Alterations of these mechanisms may induce: permanent structural alterations of organs resulting from sub-optimal concentrations of an important factor during a critical period of development; persistent structural and/or metabolic alterations due to epigenetic changes leading to alterations in gene expression; permanent effects on cellular aging regulation. The phenomenon known as "foetal programming" implies that nutritional and/or hormonal changes in the embryo-foetal microenvironment may affect the foetal genomic expression and exert permanent effects on a wide range of physiological processes [8].…”

The importance of epigenetic factors for the diagnostics and treatment of type 2 diabetes mellitus

“…Nutrition of a woman during pregnancy influence the risk of the development of chronic diseases such as type 2 diabetes, obesity and cardiovascular diseases in the offspring [10]. Heijmanset et al [11] evaluated DNA methylation of peripheral blood cells of individuals whose mothers were exposed to famine around the time of conception, during the Dutch Hunger Winter in 1944-1945.…”

“…It should be emphasized that methylation of specific loci may also be caused by hyperglycemia during pregnancy, which occurs in the course of gestational diabetes [10].…”