Maternal control of early embryogenesis in mammals

Abstract

Oocyte quality is a critical factor limiting the efficiency of assisted reproductive technologies (ART) and pregnancy success in farm animals and humans. ART success is diminished with increased maternal age, suggesting a close link between poor oocyte quality and ovarian aging. However, the regulation of oocyte quality remains poorly understood. Oocyte quality is functionally linked to ART success because the maternal-to-embryonic transition (MET) is dependent on stored maternal factors, which are accumulated in oocytes during oocyte development and growth. The MET consists of critical developmental processes, including maternal RNA depletion and embryonic genome activation. In recent years, key maternal proteins encoded by maternal-effect genes have been determined, primarily using genetically modified mouse models. These proteins are implicated in various aspects of early embryonic development, including maternal mRNA degradation, epigenetic reprogramming, signal transduction, protein translation and initiation of embryonic genome activation. Species differences exist in the number of cell divisions encompassing the MET and maternal-effect genes controlling this developmental window. Perturbations of maternal control, some of which are associated with ovarian aging, result in decreased oocyte quality.

Fig. 1

Oocyte acquire developmental competence in ovarian follicles. Environmental cues, such as maternal age, diet, chemicals and health status (e.g. obesity), could impact the intra-follicular environment and thus affect the oocyte developmental competence. A variety of physiological signals (paracrine, endocrine and autocrine) play a critical role in maintaining a proper intra-folliclular environment that nurture a competent oocyte.

Fig. 2

Dynamics of key developmental events occurring during bovine preimplantation development. Shortly after fertilization and prior to 8-16 cell stage, when embryonic genome activation occurs, early embryonic development relies on maternal-stored factors due to transcriptional silencing during this period. The maternal factors are gradually degraded while the embryonic genome is gradually activated. Genome-wide DNA demethylation occurs in both male and female genomes immediately following fertilization. However, active DNA demethylation–that is independent of DNA replication, exclusively occurs in male genome while passive DNA demethylation, that is dependent on DNA replication, occurs in female genomes. At a certain point between morula and blastocyst stages, de novo DNA methylation is initiated for both male and female genomes. Throughout early embryogenesis, other epigenetic modifications, including histone variants and modifications, are also dynamically reprogrammed. The final goal of the regulation is to reprogram the highly differentiated germ cells (sperm and oocyte) to a totipotent embryo.