Epigenetic Aging of Eggs

(* MK and AW- equal contribution)

Introduction: We all age, and with us- our genome and epigenome. As we age, heterochromatin shifts and re-distributes around the genome. When old oocytes age- this results in non-disjunction of chromosomes and non-viable eggs. One of the possible mechanisms for this early 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 participates in the process of cohesin loss. Our aim is to prove that heterochromatin shift is a key factor in oocyte aging.

Materials and methods: using a mouse oocyte model- we stain oocytes for different heterochromatin markers and compare young and old females for the staining pattern. We do this in a carefully designed experimental setting with attention to the antibody specificity. In addition, we take surplus human oocytes from IVF patients and correlate age of the oocyte with the heterochromatin staining status.

Results: in all cases studied- heterochromatin stained significantly weaker in older females. Our progress with experiments showing that heterochromatin loss is involved in cohesin loss will be presented. Preliminary results for human oocytes will be discussed.

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