One of the major breakthroughs in recent DNA research is the epigenome. During growth and development, the DNA that makes up our genes accumulates chemical marks (or epigenetic changes) that determine how much or little of the genes are expressed. Thus, environmental influences can essentially modify and determine how genes are turned on and off and even whether some are expressed at all. The old beliefs that genes are “carved in stone” or that they alone determine growth and development have been disproven. Heredity versus upbringing is no longer a debate, both play an integral role in our health and who we are!
Epigenetics are changes in the DNA and proteins that bind DNA to them. These are not changes in the DNA sequence as you find with DNA mutations, but in essence, they affect the way DNA is “folded” and genes are expressed. Epigenetics are essential to typical growth and development and play a fundamental role in both normal health and disease. Although the existing data on epigenetics and female reproductive aging sheds light on some important cellular mechanisms, many questions remain unanswered. (1)
Epigenetic modifications include:
- DNA methylation,
- Histone modifications,
- Chromatin remodeling and
- Non-coding RNA action.
These are rather technical terms, but to explain in simple terms:
- DNA methylation is a biological process by which methyl groups are added to the DNA molecule. Methylation can change the activity of a DNA segment without changing the sequence.
- Histone modifications provide an important layer of regulation for chromatin functions and are critical for processes. These range from DNA replication to transcription, cell-cycle regulation to differentiation, and tissue specification during the development of numerous diseases.
- Chromatin remodeling is the dynamic modification of chromatin architecture to allow access of condensed genomic DNA to the regulatory transcription machinery proteins, and thereby control gene expression.
- Non-coding RNA action essentially involves the way genes are expressed.
The effects of people’s experiences and environments on brain architecture and long-term physical and mental health outcomes are now being studied in the context of the epigenome. There are phases in a person’s life cycle when they are particularly vulnerable to epigenetic influences. These include the making of eggs and sperm, fertilization, and early embryo development. These are also windows of opportunity for interventions during the reproductive life cycle of women to improve maternal-child health. Therefore, epigenetic influences are involved in the regulation of foetal development and the pathophysiology of adult diseases such as cancer, diabetes, obesity, and neurodevelopmental disorders. It has also been found that various epigenetic mechanisms may be involved in the pathogenesis of preeclampsia and intrauterine growth restriction.
Why do epigenetic changes increase with age?
As we age, our cells are exposed to environmental factors and are subject to negative changes in their genome through epigenetic mechanisms. Such changes accumulate over time and have been correlated with the decline observed in aging cells. Therefore, a key aspect of human health and disease is to better understand the mechanisms of epigenetic changes that occur with age, and the factors that may ease or accelerate them.
Today, more and more women are having children later, which is mainly due to social and economic factors. Combined with this, the increasing maternal age has caused a decline in fertility, and problems with pregnancy. In view of all these factors, there is an increasing demand to understand the various consequences aging has on human reproduction and to identify the biological processes that result in these changes. As part of this, age-related epigenetic changes have been found in female reproductive organs, and the effect these changes may have on reproductive outcomes forms an essential part of women’s health.
Many studies on maternal nutrition during pregnancy, or just before the embryo is implanted, have shown that nutrition has a major impact on the epigenome, as well as on the baby’s phenotype (i.e. observable traits, metabolism, behavior, or susceptibility to disease). The altered epigenetic regulation of genes is associated with an increased tendency to disease later in life. To illustrate this; a low protein diet during gestation has shown how epigenetic changes, induced by certain dietary exposures, may be associated with the development of heart disease, insulin resistance, eating disorders, obesity, and other metabolic diseases in offspring. Mothers that eat a high-fat diet during gestation produces changes in the baby’s epigenome, which increase the risk of developing diseases such as non-alcoholic fatty liver disease, diabetes, obesity, heart disease, and other chronic diseases. On the other hand, an unbalanced folate diet can induce the development of neurological diseases, and even cancer, in offspring (3).
Based on the above there is increased proof that epigenetic processes play a central role in stem cell biology and are critical for deciding how genes are expressed during cell diversification and controlling growth and development. Epigenetics not only helps in stem cell proliferation and their maturation into specialized cells, but it also plays an important role in converting the already mature cell into another cell of a different lineage.
Thus, a better understanding of the role epigenetics plays in normal development, and how these are affected by aging, may provide valuable insight into reproduction, reproductive aging, and many other important aspects of our health. There are currently 28 clinical trials researching the impact of epigenetics changes involving stem cells in cardiovascular and lung disease, fertility, and haematological cancer, to name a few (4).
References
- Zuccarello, D, et al. Epigenetics of pregnancy: looking beyond the DNA code. J Assist Reprod Genet 39, 801–816 (2022). https://doi.org/10.1007/s10815-022-02451.
- Dompe C, et al. Epigenetic Research in Stem Cell Bioengineering-Anti-Cancer Therapy, Regenerative and Reconstructive Medicine in Human Clinical Trials. Cancers (Basel). 2020 Apr 21;12(4):1016. doi: 10.3390/cancers12041016. PMID: 32326172; PMCID: PMC7226111.
- Peral-Sanchez I, Hojeij B, Ojeda DA, Steegers-Theunissen RPM, Willaime-Morawek S. Epigenetics in the Uterine Environment: How Maternal Diet and ART May Influence the Epigenome in the Offspring with Long-Term Health Consequences. Genes. 2022; 13(1):31. https://doi.org/10.3390/genes13010031
- https://clinicaltrials.gov/search?cond=epigenetics%20&term=stem%20cells&limit=100&page=1
