Reproduction Abstracts

Mammalian reproduction is dependent on a myriad of genes, all of which must be carefully regulated spatially and temporally to ensure successful fertilization and embryonic development. Chromatin remodellers are able to affect nuclear processes such as gene transcription, DNA replication, recombination and repair through modulation of chromatin structure. Mice with hypomorphic mutations in the chromatin remodelling gene Cecr2 have normal reproductive histology and their gametes have no obvious abnormalities, yet both sexes produce significantly decreased litter sizes (by~50%) when mated to normal mice. When combined with a more deleterious Cecr2 mutation, the subfertility phenotype increases in severity. The defect in mutant males occurs around the time of fertilization: after in vivo matings, fewer oocytes/zygotes show visible pronuclei or progress to blastocyst in culture. To address whether fertilization itself is impaired or early post-fertilization remodelling events are affected, zygotes are being examined within hours of mating using phalloidin, tubulin and DAPI staining to visualize the fertilization cap and polar body formation as well as early chromatin remodelling events. In contrast, oocytes from mutant females do not show reduced pronuclei formation, indicating that the female subfertility is not due to a defect at the time of fertilization but rather to embryonic loss during development. However, an increase in embryonic resorptions is not observed, suggesting that embryos are being lost before or during implantation. Investigating the cause of subfertility in both sexes will advance our understanding of the various roles that chromatin remodelling plays in gametogenesis, fertilization, and early development.