Premature ovarian aging in mice deficient for Gpr3

被引:106
作者
Ledent, C
Demeestere, I
Blum, D
Petermans, J
Hämäläinen, T
Smits, G
Vassart, G
机构
[1] Univ Brussels, Inst Rech Biol Humaine & Mol, B-1070 Brussels, Belgium
[2] Univ Brussels, Res Lab Human Reprod, B-1070 Brussels, Belgium
[3] Univ Brussels, Lab Expt Neurosurg, B-1070 Brussels, Belgium
[4] Univ Brussels, Dept Med Genet, Hop Erasme, B-1070 Brussels, Belgium
[5] Univ Turku, Inst Biomed, FIN-20520 Turku, Finland
关键词
infertility; meiosis; cAMP; G protein-coupled receptor; fragmented oocytes;
D O I
10.1073/pnas.0503840102
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
After becoming competent for resuming meiosis, fully developed mammalian oocytes are maintained arrested in prophase I until ovulation is triggered by the luteotropin surge. Meiotic pause has been shown to depend critically on maintenance of cAMP level in the oocyte and was recently attributed to the constitutive Gs (the heterotrimeric GTP-binding protein that activates adenylyl cyclase) signaling activity of the G protein-coupled receptor GPR3. Here we show that mice deficient for Gpr3 are unexpectedly fertile but display progressive reduction in litter size despite stable age-independent alteration of meiotic pause. Detailed analysis of the phenotype confirms premature resumption of meiosis, in vivo, in about one-third of antral follicles from Gpr3(-/-) females, independently of their age. In contrast, in aging mice, absence of GPR3 leads to severe reduction of fertility, which manifests by production of an increasing number of nondeveloping early embryos upon spontaneous ovulation and massive amounts of fragmented oocytes after superovulation. Severe worsening of the phenotype in older animals points to an additional role of GPR3 related to protection (or rescue) of oocytes from aging. Gpr3-defective mice may constitute a relevant model of premature ovarian failure due to early oocyte aging.
引用
收藏
页码:8922 / 8926
页数:5
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