Epigenetic regulation of oocyte function and developmental potential

Abstract

Epigenetic regulation is complex, integrating transcriptional states of chromatin together with structural information influencing function and genome integrity. Some of these modifications are temporal lasting minutes or hours while others are heritable. The DNA content of all nucleated cells in an organism is nearly identical yet myriad cell types derive from the zygote, having followed the blueprint to generate all cell types of the adult. The orderly unfurling of this program of development with progressively restricted cellular plasticity, while maintaining cellular identity, requires mechanisms that uphold these heritable changes. Remarkably within these strict guidelines the germline and the early embryo reprogram their epigenetic information to restore pluripotency. While detailed information is not yet available for high-resolution analysis of chromatin profiles focussing on histone modifications, great advances have been made investigating DNA modifications during oogenesis and early development. These studies confirmed that differentially methylated regions, well beyond the cohort of imprinted genes, were affected with >1000 CpG islands acquiring their DNA methylation late in oogenesis. Moreover, in the mouse, as many as 15% of these methylated targets are maintained up to the blastocyct stage and are hence transgenerationally inherited. These reprogramming periods may be particularly sensitive to environmental disturbance and nutritional states making procedures such as those in the treatment of human infertility especially susceptible to epigenetic alterations that may be inherited and transmitted to future generations. This chapter describes some of the most important aspects and exciting new discoveries in epigenetic regulation in oocytes and embryos and highlights their implications in the treatment of human infertility by assisted reproductive technologies.