A new model of reproductive aging: the decline in ovarian non-growing follicle number from birth to menopause
A new model of reproductive aging: the decline in ovarian non-growing follicle number from birth to menopause
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DOI：
10.1093/humrep/dem408
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发表时间：
2008-03-01
影响因子：
6.1
通讯作者：
Klein, Nancy A.
中科院分区：
文献类型：
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作者：
Hansen, Karl R.;Knowlton, Nicholas S.;Klein, Nancy A.
背景技术背景：女性生育年龄的主要决定因素是卵巢非生长（原始，中间和初级）卵泡（NGF）的数量。为了更好地描述与衰老相关的神经生长因子数量的下降，我们采用现代体视学技术来确定从出生到绝经的妇女的神经生长因子数量。方法：收集122名妇女（年龄0-51岁）接受选择性卵巢切除术，器官捐献或尸检的正常人卵巢。在大体病理学检查后，利用系统随机取样获得组织，通过分馏器/光学分离器方法进行分析。构建并评估了描述所产生的衰减曲线的模型。研究结果：通过简单的幂函数最好地描述了NGF衰减：log（y）= ax（B）+ c，其中a、B和c是常数，y =年龄x时的NGF计数（R-2 = 0.84，119个自由度上的误差平方和= 28.18）。这个模型意味着卵泡随着年龄的增长而衰减得更快。结论：与以前的卵泡耗竭模型不同，我们的模型预测衰变率没有突然变化，而是不断增加。该模型不仅与观察到的女性绝经年龄一致，而且比以前的模型更具生物学合理性。虽然该模型与早期的尝试相比有了显着的改善，但女性之间相当大比例的NGF数量变化不能仅用年龄来解释。
BACKGROUND: The primary determinant of reproductive age in women is the number of ovarian non-growing (primordial, intermediate and primary) follicles (NGFs). To better characterize the decline in NGF number associated with aging, we have employed modern stereology techniques to determine NGF number in women from birth to menopause. METHODS: Normal human ovaries were collected from 122 women (aged 0-51 years) undergoing elective oophorectomy, organ donation or autopsy. After gross pathologic examination, systematic random sampling was utilized to obtain tissue for analysis by the fractionator/optical disector method. Models to describe the resulting decay curve were constructed and evaluated. RESULTS: NGF decay was best described by a simple power function: log (y) = ax(b) + c, where a, b and c are constants and y = NGF count at age x (R-2 = 0.84, Sums of Squares Error = 28.18 on 119 degrees of freedom). This model implies that follicles decay faster with increasing age. CONCLUSIONS: Unlike previous models of ovarian follicle depletion, our model predicts no sudden change in decay rate, but rather a constantly increasing rate. The model not only agrees well with observed ages of menopause in women, but also is more biologically plausible than previous models. Although the model represents a significant improvement compared with earlier attempts, a considerable percentage of the variation in NGF number between women cannot be explained by age alone.