Article (Scientific journals)
Loss of oocytes due to conditional ablation of Murine double minute 2 (Mdm2) gene is p53-dependent and results in female sterility.
Livera, Gabriel; Uzbekov, Rustem; Jarrier, Peggy et al.
2016In FEBS Letters, 590 (16), p. 2566-74
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Keywords :
Mdm2; female fertility; oocyte; ovary; p53
Abstract :
[en] Murine double minute 2 and 4 (Mdm2, Mdm4) are major p53-negative regulators, preventing thus uncontrolled apoptosis induction in numerous cell types, although their function in the female germ line has received little attention. In the present work, we have generated mice with specific invalidation of Mdm2 and Mdm4 genes in the mouse oocyte (Mdm2(Ocko) and Mdm4(Ocko) mice), to test their implication in survival of these germ cells. Most of the Mdm2(Ocko) but not Mdm4(Ocko) mice were sterile, with a dramatic reduction of the weight of ovaries and genital tract, a strong increase in follicle-stimulating hormone and luteinizing hormone serum levels, and a reduction of anti-mullerian hormone serum levels. Histological analyses revealed an obvious decrease of the number of growing follicles beyond the primary stage in Mdm2(Ocko) ovaries in comparison to controls, with a pronounced increase in the apparition of primary atretic follicles, most being devoid of oocyte. Similar phenotypes were observed with Mdm2(Ocko) Mdm4(Ocko) ovaries, with no worsening of the phenotype. However, we failed to detect any increase in p53 level in mutant oocytes, nor any other apoptotic marker, introgression of this targeted invalidation in p53-/- mice restored the fertility of females. This study is the first to show that Mdm2, but not Mdm4, has a critical role in oocyte survival and would be involved in premature ovarian insufficiency phenotype.
Disciplines :
Anatomy (cytology, histology, embryology...) & physiology
Endocrinology, metabolism & nutrition
Pediatrics
Author, co-author :
Livera, Gabriel
Uzbekov, Rustem
Jarrier, Peggy
Fouchecourt, Sophie
Duquenne, Clotilde
Parent, Anne-Simone ;  Université de Liège > Département des sciences cliniques > Pédiatrie
Marine, Jean-Christophe
Monget, Philippe
Language :
English
Title :
Loss of oocytes due to conditional ablation of Murine double minute 2 (Mdm2) gene is p53-dependent and results in female sterility.
Publication date :
August 2016
Journal title :
FEBS Letters
ISSN :
0014-5793
eISSN :
1873-3468
Publisher :
Wiley-Blackwell, United States
Volume :
590
Issue :
16
Pages :
2566-74
Peer reviewed :
Peer Reviewed verified by ORBi
Commentary :
(c) 2016 Federation of European Biochemical Societies.
Available on ORBi :
since 20 January 2017

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