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Oocyte attrition
1INRA-URA CNRS 1291, PRMD, 37380, Nouzilly, France.
Abstract:
During oogenesis, germ cell numbers sharply decrease when meiosis is initiated. There is solid evidence (DNA ladders, in situ detection) that this loss is through apoptosis. Oocyte apoptosis appears to hit mitotic primordial germ cells (PGC), pachytene oocytes and early primordial follicles. The control of oocyte apoptosis is not fully understood, although survival factors (LIF, kit ligand and FGF), as well as death inducing factors (fas ligand, TGFbeta), have been identified. Fas ligand binding on oocytic fas may result in caspase 8 activation. Two pathways inducing oocyte apoptosis may then be operating. In the first one, activated caspase 8 will induce activation of executioner caspases. In the second one, activated caspase 8 will trigger the cleavage of the bcl(2) family member Bid, which will act on mitochondria, resulting in cytochrome c release, caspase 9 activation and finally, activation of all executioner caspases. As a consequence of caspase activation, alterations in the cell nucleus (DNAse activation, PARP fragmentation), in the cell cytoskeleton (lamin) and cell metabolism will occur, producing cell death. During folliculogenesis, germ cell loss, owing to oocyte apoptosis, has been postulated within primordial and preantral follicles. Its regulatory mechanisms may be even more complex than those operating in foetal oocytes since additional control factors include EGF/TGFalpha and bcl(2) (survival) and activin (death inducer). In contrast, oocytes from antral follicles appear to be very unsensitive to death inducing stimuli.
Insights
Oocyte apoptosis, a programmed cell death process, significantly reduces germ cell numbers during oogenesis and folliculogenesis. Understanding its regulatory factors is crucial for reproductive health.
Area of Science:
- Reproductive Biology
- Cellular Biology
- Developmental Biology
Background:
- Germ cell numbers decrease sharply during oogenesis initiation, primarily through apoptosis.
- Oocyte apoptosis affects primordial germ cells (PGCs), pachytene oocytes, and early primordial follicles.
- While survival (LIF, kit ligand, FGF) and death factors (fas ligand, TGFbeta) are known, oocyte apoptosis control remains incompletely understood.
Purpose of the Study:
- To elucidate the mechanisms and regulatory pathways of oocyte apoptosis during oogenesis and folliculogenesis.
- To identify key factors influencing germ cell loss through programmed cell death.
- To understand the differential sensitivity of oocytes to apoptosis at various developmental stages.
Main Methods:
- Evidence for apoptosis includes DNA ladders and in situ detection.
- Analysis of signaling pathways involving caspases (caspase 8, caspase 9) and Bcl-2 family members (Bid).
- Investigation of regulatory factors like LIF, kit ligand, FGF, fas ligand, TGFbeta, EGF/TGFalpha, bcl(2), and activin.
Main Results:
- Oocyte apoptosis involves caspase activation, leading to nuclear, cytoskeletal, and metabolic alterations.
- Two main apoptotic pathways are proposed: direct executioner caspase activation or mitochondrial pathway via Bid cleavage.
- Germ cell loss via apoptosis is postulated in primordial and preantral follicles, with complex regulatory mechanisms.
Conclusions:
- Oocyte apoptosis is a significant factor in germ cell reduction during oogenesis and folliculogenesis.
- The process is regulated by a complex interplay of survival and death-inducing factors.
- Oocytes in antral follicles exhibit resistance to apoptosis-inducing stimuli.