Mondal Anupam, Tcherniak Evelina, Kolomeisky Anatoly B
Center for Theoretical Biological Physics, Rice University, Houston, Texas; Department of Chemistry, Rice University, Houston, Texas.
Department of Chemistry, Rice University, Houston, Texas.
Biophys J. 2025 Apr 1;124(7):1095-1104. doi: 10.1016/j.bpj.2025.02.004. Epub 2025 Feb 10.
Menopause marks a critically important biological event that ends a woman's fertility. It is a result of ovarian aging and depletion of ovarian reserve. Although many aspects of these processes are now well understood, the overall dynamic picture remains unclear. Here, we present a novel theoretical framework to analyze human ovarian aging dynamics and menopause timing. Our method is based on stochastic analysis of underlying processes stimulated by observing follicles sequentially transitioning between different stages during ovulation. This allows us to obtain a fully quantitative description of ovarian aging and menopause timing consistent with available experimental observations. Our model accurately predicts the average age of menopause across geographically diverse human populations. Theoretical analysis suggests a universal relation between the initial follicle reserve, the depletion rates, and the threshold that triggers menopause. In addition, it is found that the distributions of menopause times are quite narrow, and it is proposed that this might be a result of a precise regulation due to the synchronization of transitions between different stages of follicles. Our theoretical approach not only quantitatively explains the dynamics of human ovarian aging and menopause timing but also provides important insights into individual variability in ovarian aging. It can be used as a powerful tool for predicting menopause timing and investigating complex processes of reproductive aging.
更年期标志着一个极其重要的生物学事件,它结束了女性的生育能力。这是卵巢衰老和卵巢储备耗竭的结果。尽管现在对这些过程的许多方面已经有了很好的理解,但整体动态情况仍不明朗。在此,我们提出一个新的理论框架来分析人类卵巢衰老动态和更年期时间。我们的方法基于对排卵过程中卵泡在不同阶段顺序转变所激发的潜在过程的随机分析。这使我们能够获得与现有实验观察结果一致的卵巢衰老和更年期时间的完全定量描述。我们的模型准确预测了不同地理区域人类群体的平均更年期年龄。理论分析表明初始卵泡储备、耗竭率和触发更年期的阈值之间存在普遍关系。此外,发现更年期时间的分布相当狭窄,并提出这可能是由于卵泡不同阶段转变同步导致的精确调节的结果。我们的理论方法不仅定量解释了人类卵巢衰老和更年期时间的动态,还为卵巢衰老的个体差异提供了重要见解。它可以用作预测更年期时间和研究生殖衰老复杂过程的有力工具。