Department of Chemistry and Molecular Biology, University of Gothenburg, Gothenburg SE-405 30, Sweden.
Hum Mol Genet. 2014 Feb 15;23(4):920-8. doi: 10.1093/hmg/ddt486. Epub 2013 Oct 1.
In the mammalian ovary, progressive activation of primordial follicles serves as the source of fertilizable ova, and disorders in the development of primordial follicles lead to various ovarian diseases. However, very little is known about the developmental dynamics of primordial follicles under physiological conditions, and the fates of distinct populations of primordial follicles also remain unclear. In this study, by generating the Foxl2-CreER(T2) and Sohlh1-CreER(T2) inducible mouse models, we have specifically labeled and traced the in vivo development of two classes of primordial follicles, the first wave of simultaneously activated follicles after birth and the primordial follicles that are gradually activated in adulthood. Our results show that the first wave of follicles exists in the ovaries for ∼3 months and contributes to the onset of puberty and to early fertility. The primordial follicles at the ovarian cortex gradually replace the first wave of follicles and dominate the ovary after 3 months of age, providing fertility until the end of reproductive life. Moreover, by tracing the time periods needed for primordial follicles to reach various advanced stages in vivo, we were able to determine the exact developmental dynamics of the two classes of primordial follicles. We have now revealed the lifelong developmental dynamics of ovarian primordial follicles under physiological conditions and have clearly shown that two classes of primordial follicles follow distinct, age-dependent developmental paths and play different roles in the mammalian reproductive lifespan.
在哺乳动物的卵巢中，原始卵泡的逐步激活是可受精卵子的来源，而原始卵泡发育的障碍会导致各种卵巢疾病。然而，对于生理条件下原始卵泡的发育动态，我们知之甚少，不同群体的原始卵泡的命运也不清楚。在这项研究中，我们通过生成 Foxl2-CreER(T2) 和 Sohlh1-CreER(T2) 诱导型小鼠模型，特异性标记和追踪了两类原始卵泡的体内发育，即出生后同时激活的第一批卵泡和成年后逐渐激活的原始卵泡。我们的结果表明，第一批卵泡存在于卵巢中约 3 个月，为青春期和早期生育能力的启动做出贡献。在 3 个月大后，卵巢皮质中的原始卵泡逐渐取代第一批卵泡，并主导卵巢，提供生育能力直到生殖生命结束。此外，通过追踪原始卵泡在体内达到各种成熟阶段所需的时间，我们能够确定这两类原始卵泡的精确发育动态。我们现在揭示了生理条件下卵巢原始卵泡的终身发育动态，并清楚地表明，两类原始卵泡遵循不同的、依赖年龄的发育途径，在哺乳动物的生殖寿命中发挥不同的作用。
