Oocyte maturation and embryonic failure

Embryonic development is readily compromised by imperfections introduced during the process of oocyte maturation. We discuss the nature and causes of these imperfections, particularly in oocytes exposed to inappropriate hormonal regimes in vivo or to culture systems designed to induce the maturation of oocytes in vitro. The acquisition of developmental competence involves the synthesis and storage of a wide range of molecules during oocyte growth followed by the reprogramming and ordered utilization of these stored products during maturation, fertilization and early embryogenesis. The regulatory signals for these molecular changes are produced by the follicle cells in response to circulating levels of gonadotrophins; we report that some ovarian stimulation protocols distort these signals thereby disrupting molecular reprogramming of the oocyte and reducing subsequent developmental competence. The aspiration of immature oocytes from antral follicles followed by their maturation in vitro is a potential alternative to hormonal stimulation of patients in IVF treatment. Although relatively successful in a variety of animals, the production of fully viable human embryos by in-vitro maturation is still unsatisfactory despite the use of a wide variety of culture protocols. Our data suggests that the key to maturation and embryo viability in vitro resides in the follicle cell compartment rather than the oocyte. Because of rapid luteinization changes, follicle cells in culture probably fail to provide the maturing oocyte with the necessary ordered set of instructive signals and nutrients needed for the acquisition of developmental competence. Although much remains to be discovered about the nature, concentration and transmission of signals, nevertheless it is already clear that different steroids, matrix metalloproteinases and growth factors are involved in conferring viability on the maturing oocyte. Major improvements in the yield of viable embryos from in-vitro matured oocytes can be anticipated from a systematic analysis of somatic signals from the pre-ovulatory follicle.