Dataset Information

Caspase 9 is constitutively activated in mouse oocytes and plays a key role in oocyte elimination during meiotic prophase progression.

ABSTRACT: In many mammalian species, more than half of the initial oocyte population is eliminated by neonatal life, thus limiting the oocyte reserve for reproduction. The cause or mechanism of this major oocyte loss remains poorly understood. We examined the apoptotic pathway involved in oocyte elimination in wild-type mouse ovaries as well as in Msh5 -/- ovaries, in which all oocytes were eliminated due to a lack of double strand break repair. Immunoblot and immunofluorescence staining showed that an initiator caspase 9 and an effector caspase 7 were constitutively activated in almost all oocytes in fetal ovaries regardless of their genotypes. In caspase 9 -/- ovaries, the total number of oocytes remained high while that in wild-type ovaries steadily declined during ovarian development. Therefore, the activation of caspase 9 was required for but did not immediately lead to oocyte demise. We found that XIAP, an endogenous inhibitor of apoptosis, was also abundant in oocytes during meiotic prophase progression. On the other hand, a cleaved form of PARP1, a target of effector caspases, was localized to the nuclei of a limited number of oocytes, and the frequency of cleaved PARP1-positive oocyte nuclei increased significantly higher before all oocytes disappeared in Msh5 -/- ovaries. We conclude that the mitochondrial apoptotic pathway mediated by caspase 9 is constitutively activated in oocytes and renders the elimination of oocytes with meiotic errors, which can be captured by the cleavage of PARP1.

SUBMITTER: Ene AC

PROVIDER: S-EPMC3664362 | biostudies-literature | 2013 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Caspase 9 is constitutively activated in mouse oocytes and plays a key role in oocyte elimination during meiotic prophase progression.

Ene Adriana C AC Park Stephanie S Edelmann Winfried W Taketo Teruko T

Developmental biology 20130204 1

In many mammalian species, more than half of the initial oocyte population is eliminated by neonatal life, thus limiting the oocyte reserve for reproduction. The cause or mechanism of this major oocyte loss remains poorly understood. We examined the apoptotic pathway involved in oocyte elimination in wild-type mouse ovaries as well as in Msh5 -/- ovaries, in which all oocytes were eliminated due to a lack of double strand break repair. Immunoblot and immunofluorescence staining showed that an in ...[more]

PMID: 23384561

Similar Datasets

Project description:Chromosome segregation errors in human oocytes are the leading cause of birth defects, and the risk of aneuploid pregnancy increases dramatically as women age. Accurate segregation demands that sister chromatid cohesion remain intact for decades in human oocytes, and gradual loss of the original cohesive linkages established in fetal oocytes is proposed to be a major cause of age-dependent segregation errors. Here we demonstrate that maintenance of meiotic cohesion in Drosophila oocytes during prophase I requires an active rejuvenation program, and provide mechanistic insight into the molecular events that underlie rejuvenation. Gal4/UAS inducible knockdown of the cohesion establishment factor Eco after meiotic S phase, but before oocyte maturation, causes premature loss of meiotic cohesion, resulting in destabilization of chiasmata and subsequent missegregation of recombinant homologs. Reduction of individual cohesin subunits or the cohesin loader Nipped B during prophase I leads to similar defects. These data indicate that loading of newly synthesized replacement cohesin rings by Nipped B and establishment of new cohesive linkages by the acetyltransferase Eco must occur during prophase I to maintain cohesion in oocytes. Moreover, we show that rejuvenation of meiotic cohesion does not depend on the programmed induction of meiotic double strand breaks that occurs during early prophase I, and is therefore mechanistically distinct from the DNA damage cohesion re-establishment pathway identified in G2 vegetative yeast cells. Our work provides the first evidence that new cohesive linkages are established in Drosophila oocytes after meiotic S phase, and that these are required for accurate chromosome segregation. If such a pathway also operates in human oocytes, meiotic cohesion defects may become pronounced in a woman's thirties, not because the original cohesive linkages finally give out, but because the rejuvenation program can no longer supply new cohesive linkages at the same rate at which they are lost.

Dataset Information

Caspase 9 is constitutively activated in mouse oocytes and plays a key role in oocyte elimination during meiotic prophase progression.

Publications

Caspase 9 is constitutively activated in mouse oocytes and plays a key role in oocyte elimination during meiotic prophase progression.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets