Deficits in female reproductive function in GH-R-KO mice; role of IGF-I
Deficits in female reproductive function in GH-R-KO mice; role of IGF-I
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DOI：
10.1210/en.140.6.2637
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发表时间：
1999-06-01
期刊：
影响因子：
4.8
通讯作者：
Bartke, A
中科院分区：
文献类型：
--
作者：
Danilovich, N;Wernsing, D;Bartke, A
GH受体/GH结合蛋白基因定向干扰的纯合子小鼠(GH-R-KO小鼠；-/-)表现出血浆IGF-I水平降低，血浆GH水平升高，以及矮小表型。尽管大多数GH-R-KO小鼠都能生育，但在-/-x-/-配对中，第一次受孕的年龄会大大推迟。在这里，我们报告了GH-R-KO小鼠阴道开放的年龄比正常小鼠显著延迟，但重组人(Rh)IGF-I治疗可以使其提前。在怀孕的GH-R-KO女性中，胎儿尺寸减小，妊娠时间延长，而胎盘重量意外增加。胎儿和胎盘重量的变化与母亲的基因有关，而与胎儿的基因无关。此外，与正常雌性相比，GH-R-KO组新生幼崽的产仔数和体重显著降低。产仔数的减少既反映了母羊的影响，也反映了母羊的影响。我们得出结论，生长激素抵抗和随之而来的外周IGF-I水平的降低与雌性青春期延迟、胎儿和胎盘生长改变、分娩延迟和产仔减少有关。
Mice homozygous for targeted disruption of the GH receptor/GH binding protein gene (GH-R-KO mice; -/-) exhibit reduced plasma IGF-I levels, elevated plasma GH levels, and dwarf phenotype. Although most GH-R-KO mice are fertile, age at first conception is greatly delayed in -/- x -/- matings. Here we report that the age of vaginal opening is significantly delayed in GH-R-KO vs. normal mice, but it can Se advanced by treatment with recombinant human (rh)IGF-I. In pregnant GH-R-KO females, fetal size is reduced and pregnancy is prolonged while placental weight is, unexpectedly, increased. Alterations in fetal and placental weight are related to maternal rather than fetal genotype. Moreover, litter size and body weight of newborn pups are significantly reduced in GH-R-KO vs. normal females. Reduction in litter size reflects both dam and sire effects. We conclude that GH resistance and consequent reduction in peripheral IGF-I levels is associated with delay of female puberty, alterations in fetal and placental growth, delay of parturition, and reduced litter size.