Dr. Saffet Öztürk, is an associate professor at Department of Histology and Embryology, Akdeniz University School of Medicine in Antalya, Turkiye.
Abstract
Recent evidence highlights a decline in fertility globally, particularly in developed countries, largely due to socioeconomic factors and couples' reproductive planning. A significant factor in this decline is ovarian aging, marked by a reduction in primordial and other follicle populations. Key mechanisms driving ovarian aging include genomic instability, telomere shortening, and epigenetic changes, particularly DNA methylation and histone modifications.
DNA methylation involves the addition of a methyl group to cytosine residues in CpG dinucleotides, influencing gene expression. Studies show that global DNA methylation levels in CpG islands are reduced in aged mice's GV oocytes, while non-CpG regions display increased methylation. Despite lower CpG methylation, gene transcription related to translational control and meiosis diminishes in aging oocytes, contributing to fertility declines.
Similarly, histone methylation, which occurs on histones H3 and H4 and is vital for numerous cellular processes, also declines with age. Research indicates a decrease in transcription-activating and repressive histone marks in both GV and MII oocytes from older organisms. Notable reductions have been observed in the activating mark H3K4me2 and in the expression of proteins critical for establishing this mark.
In conclusion, accumulating evidence indicates that both DNA and histone methylation patterns undergo age-associated alterations, which are closely linked to the progressive decline in fertility. Considering the interplay between these two epigenetic mechanisms, further investigations are warranted to clarify the molecular pathways underlying ovarian aging, particularly in the context of GV and MII oocytes.