Perhaps no two periods in a woman’s life hold greater significance and transformation power than the preconception period and pregnancy. Indeed, they demand significant physiological and behavioural adjustments. However, all these changes are only for the mother’s good and ensure that everything is right with the developing fetus. Increased awareness about the benefits of supplementation leads more women toward healthier lifestyle practices, diet changes, and focused nutrient uptake. In pregnancy, this would include essential nutrients such as vitamins, folic acid, and choline, which support metabolic functions and fetal development and contribute to epigenetic modifications in the fetal genome. Epigenetics is a very expanding field that focuses on how environmental and nutritional factors shape gene expression through mechanisms that do not alter the DNA sequence. PGx testing promises to unlock the investigation and management of epigenetic modifications in the fetal genome. Epigenetic changes in the fetal genome are discussed further in the post below.

Epigenetics

Epigenetics refers to modifications in gene expression without a change in the DNA sequence that underlies the gene. It is, more generally, an epigenetic change driven by influences of the environment, including diet, exercise, and stress, to significantly influence health outcomes. More commonly, these patterns are set early in development but are modified throughout life. Mechanisms include DNA methylation, histone modification, and chromatin remodelling. The epigenetic mechanism is shown in the diagram below.

• DNA Methylation is catalyzed by DNA methyltransferases (DNMTs) and involves adding a methyl group to the cytosine base within CpG dinucleotides. Generally, DNA methylation leads to downregulation of transcription and maintenance of gene silencing in a tissue-specific manner. The methylation status of the genome, therefore, plays a significant role in gene expression, disease susceptibility, and developmental processes. PGx Gene Test focuses on identifying genetic variations, such as single nucleotide polymorphisms (SNPs), that influence the metabolism and efficacy of medications.
• Histone modifications refer to the addition of acetyl groups through histone acetyltransferases, phosphorylation, and methylation of histones. A modified histone tail can add new acetyl, methyl, or phosphate groups on its tail to either activate or inhibit transcription. For instance, when HAT opens up chromatin, it activates genes. In contrast, histone deacetylation, with the help of HDAC, condenses the structure of chromatin while suppressing gene expression.
• Chromatin remodelling: The chromatin structure may be dynamically rearranged to change the accessibility of genes. Enzymes such as the ATP-dependent SWI/SNF complex may facilitate a loosening effect on chromatin, thus improving transcription. Polycomb group proteins help in chromatin condensation, leading to gene silencing. All these effects are highly relevant to fetal development and long-term health.

The diagram shows an overview of epigenetic mechanisms

Nutrients’ Role in Epigenetic modification

All of these epigenetic mechanisms are impacted by nutrients acquired through either diet or supplementation, which further affect fetal development and, eventually, future health outcomes. The two most important among them are choline and folic acid, which donate the methyl groups to support DNA methylation. PGx testing can provide insights into the mother’s metabolic pathways, including those involved in the one-carbon cycle.

Choline

Choline is one of the water-soluble essential nutrients involved in a multitude of physiological functions. Its role becomes far more pronounced with the progress of the pregnancy, even more so in the last trimester, of which the third falls since it is when the baby will quickly grow most of its mass in brain tissues. In many such cases, pregnant women end up with intakes at levels that are simply inadequate for choline. These women then face possible severe adverse effects on the developing fetus, including not enough brain development and rising risks of complicating the pregnancy.
Choline is a precursor of phospholipids, including an important one, which has a vital role in the structural setup of cell membranes. Also, it serves as a precursor for the synthesis of neurotransmitters like acetylcholine involved in impulse transmission by neurons and also for developing the brain. In addition to that, choline can act as a methyl group donor in the synthesis of S-adenosylmethionine, and this is an important provider of the methyl group incorporated into DNA and histone methylation. PGx Gene test information can further guide the use of the supplements, such as supplementation with folic acid choline or vitamin B12, which are quite crucial for supporting proper DNA methylation.

Epigenetic Impact:

The availability of choline during pregnancy affects DNA methylation patterns within the fetal genome. Scientists have proven that supplementation with choline affects the methylation of specific genes related to the development and function of the brain. Such changes would improve the cognitive outcome of the baby. For example, several animal experiments have shown that maternal choline supplementation enhances memory and learning abilities in offspring. It can protect against neural tube defects (NTDs) and is linked with an attenuation of the risk of developing developmental disorders like autism spectrum disorder (ASD) and schizophrenia.
Choline also impacts environmental insults, such as alcohol exposure during pregnancy. The compound enhances cognitive outcomes and lessens behavioural symptoms in offspring exposed in utero to alcohol. Additionally, it has been noted that choline supplementation decreases the fetus’s cortisol levels. This could play a role in altering the HPA axis to decrease stress-related consequences. PGx Gene test of RPh Labs can identify genetic risk factors that predispose mothers to conditions like preeclampsia, gestational diabetes, or preterm labour.

Folic Acid

Folic acid is a synthetic form of the B-vitamin folate. It is perhaps best known for preventing neural tube defects, but its importance extends far beyond that. Folate is required for DNA synthesis, repair, and methylation, and its metabolism is intimately linked with the one-carbon cycle, a series of biochemical reactions that generate methyl groups for epigenetic modifications in the fetal genome.

Epigenetic Mechanisms:

Folic acid acts as a precursor for 5-methyltetrahydrofolate, a methyl donor necessary for homocysteine-to-methionine conversion. Methionine serves as a precursor for SAM and the donor of methyl groups needed for the methylation of DNA and histones. A lack of folic acid could, therefore, inhibit these mechanisms, leading to DNA hypomethylation and altering the expressions of genes.
The epigenetic modifications in the fetal genome effects manifest themselves through involvement in the closing process of the neural tube in embryogenesis. Folic acid deficiency is also found to be related to NTDs. Furthermore, polymorphisms in folate metabolizing enzymes such as MTHFR lead to alteration of how it is used and enhance vulnerability to developmental defects.

Neurodevelopmental Benefits:

There is considerable scientific evidence that confirms that the appropriate supplementation of folic acid during pregnancy results in superior cognitive functions and a decreased possibility of neurodevelopmental disorders. The levels of folate in the mother correlate with the global DNA methylation in the offspring and further impact brain development and function. Additionally, it has been observed that the supplementation of folic acid resulted in lower prevalence rates of ASD and ADHD.
Folic acid is critical in the process of placentation. This is how the placenta forms and then attaches to the uterine wall. The invasion process by trophoblast cells and the remodelling process of maternal blood vessels are two steps involved in placentation. Folic acid enhances trophoblast invasion and promotes angiogenesis, ensuring adequate blood supply to the developing fetus. It has been implicated with complications like preeclampsia, Fetal Growth Restriction, and Placental Abruption, among many others.

Discussion

In particular, the interplay of nutrients such as choline and folic acid, in addition to epigenetic mechanisms, underlines the crucial roles of maternal nutrition in gestation. These nutrients help in the direct promotion of fetal development, whereas gene expression is affected via epigenetic modifications in the fetal genome, which may result in consequences for the health and wellness of the offspring at birth, lowering its probability of developmental disorders and pregnancy complications.
The available evidence indicates that an adequate supply of these nutrients would be beneficial for brain development, placental function, and pregnancy outcomes in general. However, more studies are needed to clarify the long-term consequences of maternal nutrition on the epigenome and how such changes would influence health during an individual’s lifetime.

Conclusion

Epigenetic modifications in the fetal genome development are essential and maternal nutrition has been recognized as a crucial factor affecting such changes. In organisms, choline and folic acid donate methyl groups critically for DNA and histone methylation, influencing gene expression and development processes. Adequate nutrient intake during pregnancy not only supports fetal development and mitigates adverse outcomes but also aids in improving overall health. The ongoing study reveals the role of nutrition in the mother and then in the future generations it creates. PGx testing represents a promising tool for optimizing medication use during pregnancy, with the potential to minimize drug-induced epigenetic modifications in the fetal genome that could affect fetal development.