Oocyte Apoptosis: Like Sand through an Hourglass

Abstract

Although the study of germ cell death is arguably still in its infancy as a field, several recent breakthroughs have provided the fodder for a story, replete with episodes of apparent mass cellular suicide if not murder, that will undoubtedly serve as a research base for many laboratories over the next several years. Death is known to strike the male and female germlines with roughly equal intensity, but the innate feature of male germ cells being self-renewing while those of the female are not places the death of oocytes in a completely different light. Indeed, the functional life span of the female gonads is defined in most species, including humans, by the size and rate of depletion of the precious endowment of oocytes enclosed within follicles in the ovaries at birth. This continuous loss of oocytes throughout life, referred to by many as the female biological clock, appears to be driven by a genetic program of cell death that is composed of players and pathways conserved from worms to humans. It is on this genetic pathway, and the role of its constituent molecules in regulating female germ cell fate, that this review will focus. Emphasis will be placed on those studies using genetic-null or transgenic models to explore the functional requirement of proteins, such as Bcl-2 family members, Apaf-1, and caspases in vertebrates to CED-9, CED-4, and CED-3 in Caenorhabditis elegans, in oocyte survival and death. Furthermore, hypotheses regarding the potential impact of translating what is now known of the oocyte death pathway into new approaches for the clinical diagnosis and management of female infertility and the menopause will be offered as a means to stimulate further research in this new and exciting field.

Does first polar body morphology predict oocyte performance during ICSI treatment?

“…Our results also show that women in group I with normal 1 PB morphology transferred embryos may have a better ovarian reserve as related to the other groups. Women with low ovarian reserve have a higher proportion of post-mature or dysmature oocytes [18]. Therefore, it could be speculated that the apoptotic process in women with low ovarian reserve is already taking place at least in some of the oocytes at the time of retrieval or denudation.…”

ATP-induced apoptosis of human granulosa luteal cells cultured in vitro

“…From these studies, a common underlying mechanism begins to emerge. A recent molecular model (40,41) indicates the central role of mitochondria in the regulation of apoptosis. When a cell is exposed to potentially lethal stimuli, such as death ligands and toxicants or stressors, the stimuli are converted to intracellular signals, which are then integrated at the level of mitochondria.…”

Germ Cell Apoptosis and DNA Damage Responses

“…Apoptosis is remarkably prevalent in germ cells. It is estimated that out of ~7,000,000 germ cells occurring in the ovaries of 5 months old human embryos only ~300,000 remain at an age of 7 years, and less than a thousand oocytes are left in the years before ovarian senescence; for review, see Tilly ( 2001 ) and Morita and Tilly ( 1999 ) . It thus appears that apoptosis is especially important during germ cell development.…”