Ornithine decarboxylase and oocyte maturation

在大多数脊椎动物物种中，包括两栖动物和哺乳动物，完全成熟的卵母细胞在排卵前立即成熟成为卵子。卵母细胞成熟的关键事件是减少染色体数量以产生单倍体雌性基因组，以便在受精后新胚胎将恢复二倍体状态。卵母细胞通过一种特殊形式的细胞分裂经历染色体减少，丢弃一半的染色体作为一个不可活的细胞（极体）。染色体的精确分离显然对产生功能卵子至关重要。然而，卵母细胞成熟被认为还包括卵母细胞健康所必需的许多蛋白质和代谢物的积累。在小鼠和人类中，健康状况不佳的卵母细胞在受精时胚胎碎裂的发生率很高，并且与着床前胚胎死亡密切相关。这些蛋白质和代谢物的特性在很大程度上是未知的。我们一直以两栖动物非洲爪蟾作为脊椎动物的模式生物来研究卵母细胞成熟，因为它比哺乳动物具有许多实验优势。我们发现两栖动物卵母细胞在成熟过程中产生了大量的鸟氨酸脱羧酶（ODC）。ODC将鸟氨酸（一种氨基酸）分解为腐胺，腐胺是一种必需的细胞代谢物，其确切功能尚不清楚。我们发现，当ODC的产生受到抑制时，卵母细胞完成极体挤压。然而，成熟卵子表现出凋亡（程序性细胞死亡）的迹象，由此产生的胚胎碎片化。我们建议使用小鼠模型来研究ODC在哺乳动物卵母细胞成熟中的作用。我们的具体目标是建立ODC在小鼠卵母细胞成熟中的生理作用，并了解ODC保持卵母细胞健康的生化机制。了解早期胚胎碎裂的生化基础是脊椎动物繁殖的基础。

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.