Epigenetic Aging of Human Oocytes
AWARD NOMINEE

Introduction: We all age, and with us our genome and epigenome. As we age, heterochromatin shifts and re-distributes around the genome. When women age, the number and quality of their oocyte decline, primarily because of an increase in meiotic non-disjunction events that increase the rate of oocyte and embryo aneuploidy. One of the possible early mechanisms of aging is related to the loss of cohesin subunits from the chromosomes, which are not re-loaded.

Aim: We hypothesize that the redistribution of heterochromatin in the nucleus with aging contributes to the process of cohesin loss. Our aim is to prove that heterochromatin shift is a key factor in oocyte aging.

Materials and methods: following our previous results in mouse oocytes, we stained human surplus GV oocytes, obtained after controlled ovarian hyper stimulation (COH) for IVF treatments, for different heterochromatin markers (Hoechst DNA stain, 5me-C and H3K9me2). We then compared the staining pattern and status between oocytes obtained from young versus old females.

Results: In all cases studied, both in mouse and human, heterochromatin stained significantly weaker in older females oocytes, and it also seemed to be more compacted. We see a significant decrease in H3K9 methylation and DNA methylation. Our progress with experiments showing that heterochromatin loss is involved in cohesin loss will be presented.

Conclusions: heterochromatin shift is not only involved in aging of highly cycling tissues, but also in oocyte aging.