Premature ovarian aging in mice deficient for Gpr3
Premature ovarian aging in mice deficient for Gpr3
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DOI：
10.1073/pnas.0503840102
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发表时间：
2005-06-21
影响因子：
11.1
通讯作者：
Vassart, G
中科院分区：
文献类型：
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作者：
Ledent, C;Demeestere, I;Vassart, G
在恢复减数分裂的能力之后，将完全发育的哺乳动物卵母细胞在先前I中被捕，直到蓝晶石激素激增触发排卵为止。减数分裂的暂停已被证明在卵母细胞中的cAMP水平维持依赖性，最近归因于GS蛋白质耦合受体GPR3的组成型GS（激活腺苷酰基环酶）信号传导活性的组成型GS（异构三聚体GTP结合蛋白）。在这里，我们表明缺乏GPR3的小鼠意外肥沃，但尽管减数分裂暂停不稳定，但仍显示出垃圾大小的逐渐减小。对表型的详细分析证实了体内减数分裂的过早恢复，在GPR3（ - / - ）雌性中，大约三分之一的肛门卵泡中，与年龄无关。相反，在衰老的小鼠中，缺乏GPR3会导致生育力严重降低，这表现出通过自发排卵和大量超大卵母细胞产生越来越多的非发展早期胚胎的产生。老年动物中表型的严重恶化表明，GPR3与卵母细胞免受衰老的保护（或救援）有关。 GPR3缺陷的小鼠可能构成由于早期卵母细胞衰老而导致的早产卵巢衰竭的相关模型。
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.