Reproduction Abstracts

Disruptions during epigenetic reprogramming in developing germ cells may result in the introduction of germline epimutations. These epimutations may cause aberrant gene expression in the developing germline and in the parent’s offspring. This project investigates the impacts of functionally depleting the essential epigenetic modifier polycomb repressive complex 2 (PRC2) on germline formation and development in the next generation. To achieve this we are examining a mouse model with a point mutation in the Eed gene, an indispensible component of PRC2. Preliminary experiments have revealed stochastic variation in somatic and germ cell phenotypes. Fertility tests show that some surviving homozygous mutant males are subfertile and exhibit germ cell loss in the adult testis, which may be due to compromised testis and/or germ cell development. Fetal germ cells display variagation of transgene silencing, indicating that transcriptional control in Eed mutant germ cells is compromised. Moreover, we observed paternal affects on transcriptional control in offspring from Eed mutant fathers. Using whole genome transcriptional analyses we identified over 2000 genes that are differentially expressed in E8.5 day embryos fathered by Eed homozygous males compared to heterozygous males. These expression differences are likely to be due to aberrant epigenetic patterning in the sperm of the father. These data provide the first evidence that PRC2 regulates transmission of epigenetic effects from the father to his offspring. Greater understanding of epigenetic mechanisms in the developing germ cells is critical for determining how epigenetic defects in the germline influence the inheritance of complex diseases in a parent’s children.