Unfortunately, real life is not a fairy tale. Unlike Sleeping Beauty, sleeping oocytes are not frozen in time. As oocytes get older, they acquire epigenetic changes that make it harder for them to get on with their baby making business. Important new single-cell multiomics work from Gavin Kelsey’s and Myriam Hemberger’s teams at the Babraham Institute shows that aging oocytes have an epigenetic timestamp.
Using single-cell M&T-seq, a cutting-edge technology previously developed at the institute that allows you to study the methylome and transcriptome side-by-side within the same cell, Juan Castillo-Fernandez and Erika Herrera-Puerta are able to distinguish an old mouse oocyte from a young mouse oocyte based on which genes are active and how chromatin is structured around these genes. They identified key epigenetic characteristics that give young oocytes a significant advantage in competency over older oocytes, as well as some that reassuringly remain impartial to age.
- Younger oocytes have a more complex and consistent transcriptome, while older oocytes’ transcriptomes show less complexity and more variability
- 560 maternal-effect genes are differentially expressed between young and old oocytes, of which 23 are linked to changes in DNA methylation
- Post-transcriptional events are presumably the cause of the age-related differential expression of most genes
- Overall, DNA methylation landscapes are globally similar between younger and older oocytes, even imprinted methylation patterns
- Old oocyte transcriptomes show low expression of maternal-effect genes and decreased developmental competency
- However, a portion of the older oocytes display young-like transcriptomes and conserved competency
The good news is that not all older oocytes are the same epigenetically, despite them being the same age timewise. This important finding could not have been discovered without their single-cell approach, had they instead pooled all the older oocytes together for their study and averaged out the results. Oocytes that sleep in a more comfortable, healthier environment, with fewer bad exposures to things like hormonal imbalances, poor nutrition, alcohol, tobacco, or drugs, will most likely age at a slower rate epigenetically and wake up refreshed when their prince comes along.
But listen up ladies, if you have trouble getting pregnant or had an unsuccessful pregnancy, it doesn’t necessarily mean that your eggs are old and gray. Many other elements need to be factored in, for instance, maybe the prince had some issues of his own. What’s so great about scM&T-seq is that it could also be applied to identify epigenetic timestamps in sperm.
Check out this eggciting work in Aging Cell, December 2020