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NLRP5 mediates mitochondrial function in mouse oocytes and embryos.
- Source :
-
Biology of reproduction [Biol Reprod] 2012 May 03; Vol. 86 (5), pp. 138, 1-10. Date of Electronic Publication: 2012 May 03 (Print Publication: 2012). - Publication Year :
- 2012
-
Abstract
- Unraveling molecular pathways responsible for regulation of early embryonic development is crucial for our understanding of female infertility. Maternal determinants that control the transition from oocyte to embryo are crucial molecules that govern developmental competence of the newly conceived zygote. We describe a series of defects that are triggered by a disruption of maternal lethal effect gene, Nlrp5. Previous studies have shown that Nlrp5 hypomorph embryos fail to develop beyond the two-cell stage. Despite its importance in preimplantation development, the mechanism by which the embryo arrest occurs remains unclear. We confirmed that Nlrp5 mutant and wild-type females possess comparable ovarian germ pool and follicular recruitment rates. However, ovulated oocytes lacking Nlrp5 have abnormal mitochondrial localization and increased activity in order to sustain physiological ATP content. This results in an accumulation of reactive oxygen species and increased cellular stress causing mitochondrial depletion. Compromised cellular state is also accompanied by increased expression of cell death inducer Bax and depletion of cytochrome c. However, neither genetic deletion (Bax/Nlrp5 double knockout) nor mimetic interference (BH4 domain or Bax inhibitory peptide) were sufficient to alleviate embryo demise caused by depletion of Nlrp5. We therefore conclude that lack of Nlrp5 in oocytes triggers premature activation of the mitochondrial pool, causing mitochondrial damage that cannot be rescued by inactivation of Bax.
- Subjects :
- Adenosine Triphosphate metabolism
Animals
Antigens genetics
Cytochromes c metabolism
Egg Proteins genetics
Embryonic Development genetics
Embryonic Development physiology
Female
Gene Expression Regulation, Developmental physiology
Mice
Mice, Knockout
Mitochondria genetics
Ovary embryology
Ovary metabolism
Reactive Oxygen Species metabolism
bcl-2-Associated X Protein biosynthesis
bcl-2-Associated X Protein genetics
Antigens metabolism
Egg Proteins metabolism
Mitochondria metabolism
Oocytes metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1529-7268
- Volume :
- 86
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Biology of reproduction
- Publication Type :
- Academic Journal
- Accession number :
- 22357545
- Full Text :
- https://doi.org/10.1095/biolreprod.111.093583