Year: 2025
Type: dissertation
Abstract: Over the past 40 years, childbearing age has risen in developed countries. Advanced maternal age (AMA), defined as 35 years or older, has been linked to negative outcomes concerning fertility, pregnancy, and childbirth. The underlying molecular mechanisms are not entirely understood. The developmental origins of the health and disease (DOHaD) hypothesis suggests that prenatal epigenetic changes, such as in DNA methylation, may predispose offspring to metabolic disorders later in life. DNA methylation is a process where a methyl group is covalently attached to cytosine and is typically associated with transcription inhibition. This literature review explores current knowledge of how AMA may alter oocyte DNA methylation and refines potential cause-and-effect relationships. Female gametes, oocytes, form during foetal development and enter meiotic arrest until puberty. During ovulation, the meiotic arrest ends as meiosis I completes. Oocytes also undergo two waves epigenetic reprogramming, global demethylation followed by remethylation. The first wave happens in the germline to remove somatic methylation while the second occurs post-fertilization to enable totipotency of the zygote. Remaining in meiotic arrest with low global methylation makes oocytes vulnerable to functional damages including mitochondrial dysfunction, oxidative stress, DNA damage, telomere shortening, and increased activity of transposable elements. Oocyte deterioration could lead to changes in the methylome. Studies show altered global methylation as well as methylation pattern changes in certain loci, such as ribosomal DNA, in aged oocytes. The concentrations of enzymes involved in methylation also correlated with these alterations. Interestingly, changes in DNA methylation patterns are linked to other effects of ageing in the oocyte including chromosomal misalignment as well as disturbances in imprinting and epigenetic reprogramming. These findings have shown that DNA methylation could be one of the mechanisms that mediates the effect of AMA on phenotype although further research on the topic is needed.
Author: Davidson, Annika
Institutions: Tampere University, University of Tampere
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W7133024656