Lifestyle and Environment · Nutrition and Metabolic Health
Abstract
Following Barker's observations of an association between birth size and later adult diseases, considerable efforts have been made to define the characteristics of low birth weight groups in childhood. In this review, the phenotypic and biochemical characteristics during childhood of three low birth weight groups are summarized: children born following inviter fertilization (IVF), small for gestational age (SGA), or very premature. Each of these groups is likely to have been exposed to an adverse environment at different developmental stages. The triggers and mechanisms leading to programmed changes in growth, development, and metabolism of these groups of children have yet to be identified. Epigenetics has been proposed as a potential mechanism for these programmed changes through environmentally induced changes in gene expression. Data from animal models in which environmental, particularly nutritional, manipulation leads to changes in DNA methylation are presented. The relevance of these animal studies to IVF, SGA, and very premature children are discussed as are potential candidate genes that may have undergone epigenetic modification to alter growth and metabolism.
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By this author
Iodine and fertility: do we know enough?
Mathews DM et al., 2021 · Human reproduction (Oxford, England)
Iodine is a vital micronutrient and its importance in thyroid function is well established. However, abnormalities in iodine intake may also have other effects. In particular, iodine is taken up avidly by the ovary and endometrium. Iodine deficiency is associated with reduced fertility. The use of high iodine concentration contrast media has recently been shown to improve conception rates in couples with unexplained infertility (UI). We hypothesize that this improvement could be related to the iodine excess and mechanisms independent of its action on thyroid. In this article, the metabolism of iodine and its potential role in fertility will be discussed, including the impact of both iodine deficiency and excess states and the importance of iodine in normal fetal development. This will include insights from animal studies on the effect of iodine in the uterine and ovarian structural environment, hormonal milieu and immunological factors affecting implantation. We speculate that iodine may well have a role as a potential therapy for UI.
Related research
Epigenetics of pregnancy: looking beyond the DNA code
Zuccarello D et al., 2022 · Journal of assisted reproduction and genetics · Free full text on PubMed Central
Epigenetics is the branch of genetics that studies the different mechanisms that influence gene expression without direct modification of the DNA sequence. An ever-increasing amount of evidence suggests that such regulatory processes may play a pivotal role both in the initiation of pregnancy and in the later processes of embryonic and fetal development, thus determining long-term effects even in adult life. In this narrative review, we summarize the current knowledge on the role of epigenetics in pregnancy, from its most studied and well-known mechanisms to the new frontiers of epigenetic regulation, such as the role of ncRNAs and the effects of the gestational environment on fetal brain development. Epigenetic mechanisms in pregnancy are a dynamic phenomenon that responds both to maternal-fetal and environmental factors, which can influence and modify the embryo-fetal development during the various gestational phases. Therefore, we also recapitulate the effects of the most notable environmental factors that can affect pregnancy and prenatal development, such as maternal nutrition, stress hormones, microbiome, and teratogens, focusing on their ability to cause epigenetic modifications in the gestational environment and ultimately in the fetus. Despite the promising advancements in the knowledge of epigenetics in pregnancy, more experience and data on this topic are still needed. A better understanding of epigenetic regulation in pregnancy could in fact prove valuable towards a better management of both physiological pregnancies and assisted reproduction treatments, other than allowing to better comprehend the origin of multifactorial pathological conditions such as neurodevelopmental disorders.
Epigenetic Influences During the Periconception Period and Assisted Reproduction
Amoako AA et al., 2017 · Advances in experimental medicine and biology
The periconception period starts 6 months before conception and lasts until the tenth week of gestation. In this chapter, we will focus on epigenetic modifications to DNA and gene expression within this period and during assisted reproduction. There are two critical times during the periconception window when significant epigenetic 'reprogramming' occur: one during gametogenesis and another during the pre-implantation embryonic stage. Furthermore, assisted conception treatments, laboratory protocols and culture media can affect the embryo development and birth weights in laboratory animals. There is, however, an ongoing debate as to whether epigenetic changes in humans, causing embryo mal-development, placenta dysfunction and birth defects, result from assisted reproductive technologies or are consequences of pre-existing medical and/or genetic conditions in the parents. The periconception period starts from ovarian folliculogenesis, through resumption of oogenesis, fertilisation, peri-implantation embryo development, embryogenesis until the end of organogenesis. In men, it is the period from spermatogenesis to epididymal sperm storage and fertilisation. Gametes and developing embryos are sensitive to environmental factors during this period, and epigenetic modifications can occur in response to adverse lifestyles and environmental factors. We now know that lifestyle factors such as advanced parentage age, obesity or undernutrition, smoking, excessive alcohol and caffeine intake and recreational drugs used during gamete production and embryogenesis could induce epigenetic alterations, which could impact adversely on pregnancy outcomes and health of the offspring. Furthermore, these can also result in a permanent and irreversible effect in a dose-dependent manner, which can be passed on to the future generations.
Epigenetic imprinting during assisted reproductive technologies: The effect of temporal and cumulative fluctuations in methionine cycling on the DNA methylation state
Hoeijmakers L et al., 2016 · Molecular Reproduction and Development
SUMMARYAssisted reproductive technology (ART) exposes gametes and embryos to an artificial environment that does not resemble the conditions of natural conception, and therefore might change epigenetic regulation of genes that are imprinted during development. In the present review, we discuss the relationship between susceptibility of specific genes to receive an altered epigenetic composition during ART processes, possibly via alterations in the biochemical folate and methionine cycle. We provide a comprehensive view of the current state of epigenetic patterning in ART‐conceived healthy children and in Angelman syndrome (AS) and Beckwith–Wiedemann syndrome (BWS) patients. We illustrate that similar genes—that is, MEST, KCNQ1OT1, and IGF2—possess an altered DNA methylation profile in animal models, ART‐conceived healthy children, and AS and BWS patients. The developmental stage at which these genes receive their epigenetic imprint appears to coincide with the specific moment that ART takes place. We highlight that ART procedures affect physiological levels of enzymes and substrates involved in the folate and methionine cycle thereby altering the DNA methylation state. Moreover, although the DNA methylation rate appears to be robust: (i) temporal imbalances coinciding with defined moments of epigenetic imprinting of specific genes affect the eventual DNA methylation state of those genes and (ii) cumulative ART effects on methionine and folate cycling can alter DNA methylation rates. These observations underscore the necessity to further investigate consequences of ART treatments on the epigenetic profile. Mol. Reprod. Dev. 83: 94–107, 2016. © 2015 Wiley Periodicals, Inc.
DNA methylation in newborns conceived by assisted reproductive technology
Håberg SE et al., 2022 · Nature communications · Free full text on PubMed Central
Assisted reproductive technology (ART) may affect fetal development through epigenetic mechanisms as the timing of ART procedures coincides with the extensive epigenetic remodeling occurring between fertilization and embryo implantation. However, it is unknown to what extent ART procedures alter the fetal epigenome. Underlying parental characteristics and subfertility may also play a role. Here we identify differences in cord blood DNA methylation, measured using the Illumina EPIC platform, between 962 ART conceived and 983 naturally conceived singleton newborns. We show that ART conceived newborns display widespread differences in DNA methylation, and overall less methylation across the genome. There were 607 genome-wide differentially methylated CpGs. We find differences in 176 known genes, including genes related to growth, neurodevelopment, and other health outcomes that have been associated with ART. Both fresh and frozen embryo transfer show DNA methylation differences. Associations persist after controlling for parents' DNA methylation, and are not explained by parental subfertility.