Poster Presentation The Annual Scientific Meeting of the Endocrine Society of Australia and the Society for Reproductive Biology 2014

Novel epigenetic mechanisms regulating male reproduction and paternal inheritance (#306)

Jessica Stringer 1 , Sam Forstor 2 , Moira K O’BRYAN 3 , Patrick S Western 1
  1. Centre for Genetic Diseases, MIMR-PHI Institute of Medical Research, Clayton, Vic, Australia
  2. Centre for Innate Immunity and Infectious Diseases, MIMR-PHI Institute of Medical Research, Clayton, Vic, Australia
  3. Department of Anatomy and Developmental Biology, Monash University, Clayton, Victoria, Australia

The developing germline plays a key role in programming epigenetic information, and transmitting this information to the offspring. Errors in epigenetic programming may result in epimutations that disrupt germline development, affecting reproductive health and fertility. More significantly, germline epimutations may be inherited and alter gene expression 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 identified that while male germ cell markers were detected in the developing testis, cords were not well defined in some Eed mutant embryos. In addition, fertility tests showed that some homozygous mutant adult males were subfertile, exhibited germ cell loss and had abnormal testis weights. Interestingly, fetal germ cells displayed variagation of transgene silencing, indicating that transcriptional control in Eed mutant germ cells is compromised. These phenotypes indicate that testis and male germ cell development is altered in Eed mutant animals. To determine whether loss of EED function in the father affects development, we used whole genome transcriptional analyses to determine transcriptional state in the offspring. We identified over 2000 genes that were 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 male reproduction and the transmission of epigenetic information from father to 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 disease.