Ornithine decarboxylase and oocyte maturation

点击翻译按钮获取中文摘要

In most vertebrate species including amphibians and mammals, fully grown oocytes undergo maturation to become eggs immediately prior to ovulation. The key event of oocyte maturation is to reduce the number of chromosomes to produce a haploid female genome so that upon fertilization the new embryos will resume a diploid state. The oocyte undergoes chromosome reduction by a special form of cell division to discard half the chromosomes as a non-viable cell (polar body). Accurate segregation of chromosomes is clearly essential for producing functional eggs. However, oocyte maturation is thought to also include the accumulation of many proteins and metabolites essential for oocyte health. Oocytes of poor health exhibit high incidence of embryo fragmentation upon fertilization in both mouse and in human and is strongly associated with pre-implantation embryonic death. The identities of these proteins and metabolites are largely unknown. We have been studying oocyte maturation using the amphibian Xenopus laevis as a vertebrate model organism for the many experimental advantages over mammalian species. We have discovered that the amphibian oocytes produced massive amounts of an enzyme called ornithine decarboxylase (ODC) during maturation. ODC breaks down ornithine (an amino acid) to putrescine, an essential cell metabolite whose exact function remains unclear. We found that when ODC production was inhibited, the oocytes completed polar body extrusion. However, the mature eggs exhibited sign of apoptosis (programmed cell death) and the resultant embryos were fragmented. We propose to investigate the role of ODC in oocyte maturation in mammals, using the mouse model. Our specific goals are to establish a physiological role for ODC in mouse oocyte maturation and to understand the biochemical mechanism by which ODC preserves oocyte health. Understanding the biochemical basis of early embryo fragmentation is fundamental in vertebrate reproduction.