Epigenetic Modifications at the Center of the Barker Hypothesis and Their Transgenerational Implications

Abstract

Embryo/fetal nutrition and the environment in the reproductive tract influence the subsequent risk of developing adult diseases and disorders, as formulated in the Barker hypothesis. Metabolic syndrome, obesity, heart disease, and hypertension in adulthood have all been linked to unwanted epigenetic programing in embryos and fetuses. Multiple studies support the conclusion that environmental challenges, such as a maternal low-protein diet, can change one-carbon amino acid metabolism and, thus, alter histone and DNA epigenetic modifications. Since histones influence gene expression and the program of embryo development, these epigenetic changes likely contribute to the risk of adult disease onset not just in the directly affected offspring, but for multiple generations to come. In this paper, we hypothesize that the effects of parental nutritional status on fetal epigenetic programming are transgenerational and warrant further investigation. Numerous studies supporting this hypothesis are reviewed, and potential research techniques to study these transgenerational epigenetic effects are offered.

Polyploidy as a Fundamental Phenomenon in Evolution, Development, Adaptation and Diseases

“…It is well established that developmental programming operates via epigenetic changes in chromatin architecture, DNA methylation, microRNA expression, histone modifications, and others [ 138 , 139 , 140 , 141 , 142 , 143 ]. We hypothesized that somatic polyploidy can be one of the epigenetic mechanisms of developmental programming in slowly renewing and terminally differentiated organs.…”

“…We hypothesized that somatic polyploidy can be one of the epigenetic mechanisms of developmental programming in slowly renewing and terminally differentiated organs. This suggestion is based on the similarity between the properties of polyploidy and the mechanisms of developmental programming described in the literature [ 131 , 132 , 140 , 141 , 144 ].…”

“…The level of ploidy, particularly in cardiomyocytes, responds to the well-established stimuli of developmental programming (including adverse growth conditions, increased functional load, inflammation, and malnutrition) similarly in the various species and various cells [ 9 , 71 , 132 , 141 ]. For example, in mammal hepatocytes, cardiomyocytes, retinocytes, and drosophila somatic cells, polyploidy is associated with the increased response to stress, activated pathways of morphogenesis and glycolytic metabolism, and the weakened aerobic metabolism and apoptosis [ 3 , 11 , 112 , 146 ].…”

The inter- and multi- generational epigenetic alterations induced by maternal cadmium exposure

“…Mechanistically, epigenetic alterations highlight these adverse disease outcomes. Due to environmental or maternal lifestyle factors, these modifications have been shown to significantly induce offspring metabolic syndrome, obesity, heart disease, and hypertension ( Ryznar et al, 2021 ). An accumulation of data has demonstrated that prenatal cadmium exposure induces many epigenetic alterations, such as DNA methylation and post-translational histone modifications, as well as influences on differential micro-RNA expression within the developing offspring ( Vilahur et al, 2015 ).…”

Role of Prenatal Nutrition in the Development of Insulin Resistance in Children

“…Epigenetic changes determine modifications in the gene expression and, consequently, in the metabolic programming of the fetus, predisposing it to the onset of metabolic diseases later in life. It has been observed that the early stages of embryo development represent a time window in which cells are most susceptible to epigenetic changes [ 21 ]. However, despite the fact that the first trimester represents a crucial period in the metabolic programming of the fetus, it is also true that fetal exposure to unfavorable intra-uterine conditions continues to influence epigenetic modifications in the next stages of development.…”