Epigenetic inheritance is a topic of importance in epigenetic research. Can we really pass on epigenetic marks to our offspring? Can this occur during pregnancy? Several epigenetic studies have shown that maternal behaviors and nutrition can have lifelong health effects on their children.
What is Epigenetics?
Epigenetics is the branch of genetics that studies the different mechanisms that influence gene expression without direct modification of the DNA sequence. Such regulatory processes may play a pivotal role both in the initiation of pregnancy and later in the embryonic and fetal development, thus determining long-term effects even in adult life according to the authors of Epigenetics of pregnancy: looking beyond the DNA code. In pregnancy however, epigenetic mechanisms are a phenomenon that responds both to maternal-fetal and environmental factors. These factors can influence and modify the embryo-fetal development during the various gestational phases. Therefore, we take a look at the effects of the most notable environmental factors that can affect pregnancy and prenatal development, such as maternal nutrition and teratogens.
Epigenetic Mechanisms
As reported by Epigenetics of pregnancy: looking beyond the DNA code, the epigenetic modulation of gene expression begins in the gametes through genomic imprinting and continues throughout the entire gestation with changes to the fetal and maternal methyloma and the specific action of the ncRNA system. The main processes involved in the epigenetic regulation of pregnancy are DNA methylation, histone post-translational modifications, the non-coding RNA, and genomic imprinting. DNA methylation is the most widespread epigenetic modification of the human genome. The addition of a methyl group to the fifth carbon of the pyrimidine cytosine ring determines long-term silencing in processes such as genomic imprinting, X- chromosome inactivation, tissue-specific regulation of gene expression, and silencing repetitive DNA elements. Correct patterns of DNA methylation prenatally and postnatally are both required for normal human development. Genomic imprinting is also an important part of fetal development. The disruption of genomic imprinting leads to established human diseases with recognizable clinical features such as Prader-Willi syndrome, Angelman syndrome, and Beckwith-Wiedemann syndrome to name a few. Disturbed genomic imprinting and its relevance for human reproduction: causes and clinical consequences states that more subtle and less dramatic changes in the imprinted patterns, especially concerning multi-locus imprinting disturbances, can instead modulate fetal growth, resource acquisition, and organogenesis.
Maternal Nutrition
According to Epigenetics of pregnancy: looking beyond the DNA code, altered maternal nutrition may induce epigenetic changes in the global expression pattern of the fetus, which triggers biological as well as psychological alterations in the offspring's lifelong outcomes. Examples of epigenetic effects based off of maternal nutrition would include not having folic acid in the mothers' diet. Not including folic acid into a pregnant woman's diet can cause neural tube defects in the fetus. The formation and closure of the neural tube is an extremely important event in the embryo's development, and incomplete development can lead to malformations and may cause conditions such as spina bifida. Best states in his article The Epigenetics of Normal Pregnancy, that "deficiencies in the intake of folic acid have been linked to neural tube defects for a long time and recent studies suggest that this may have an epigenetic component". Bests article goes on to state that folic acid is required for the production of S-adenosyl methionine (SAM). SAM is the molecules that donates the methyl group when DNA methyltransferases modify DNA.
Teratogens and Pregnancy
In addition to stress, nutrients, other environmental factors such as medications, alcohol or substances of abuse, produce changes in the global pattern of gene expression as well as hormonal imbalance, and ultimately adverse effects on embryonic development. According to Epigenetics of pregnancy: looking beyond the DNA code, one of the best known and most studied teratogens is ethanol, for it can cause a wide range of developmental abnormalities. Alcohol-related neonatal abnormalities are commonly referred to as fetal alcohol spectrum disorder (FASD). Grewal states in his article Maternal periconceptional smoking and alcohol consumption and risk for select congenital anomalies, that the most severe form of FASD is called fetal alcohol syndrome or FAS. FAS manifests as growth retardation, facial abnormalities, and central nervous system deficiencies. There is no specific time point during gestation when alcohol exposure is not accompanied by harmful consequences, the exposure during early embryonic stage is correlated with the most severe birth defects. Alcohol also induces alterations in the DNA methylome of the hypothalamus, including several differentially methylated regions (DMRs) that could underlie some of the deficits seen in FASD. According to the Cleveland Clinic Teratogens: Effects, Types, Risks & Prevention, 4-5% of congenital disorders are caused by teratogens. This may seem like a miniscule amount, but out of the world's population of 8.1 billion people, 5% is 405 million people who suffer the consequences of being exposed to teratogens in utero.
The knowledge regarding the fetal-maternal cross is rapidly expanding and an ever-increasing amount of evidence has been highlighting the importance of epigenetic regulation both in determining the effectiveness of early impregnation processes and in influencing fetal development. A better understanding of the role of epigenetic agents in embryonic development may ultimately improve counseling in pregnant people struggling with addiction, provide new pharmacological treatments to favor the early phases of the pregnancy, and allow a better recognition and management of potentially harmful factors with regards to fetal development.
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