Niikura Yuichi, Niikura Teruko, Tilly Jonathan L
Vincent Center for Reproductive Biology, Vincent Obstetrics and Gynecology Service, Massachusetts General Hospital/Harvard Medical School, Boston, MA 02114, USA.
Aging (Albany NY). 2009 Dec 12;1(12):971-8. doi: 10.18632/aging.100105.
Of all the major organ systems in the body, the ovaries of females are the first to exhibit impaired function with advancing age. Until recently, traditional thinking was that female mammals are provided with a non-renewable pool of oocyte-containing follicles at birth that are depleted during postnatal life to exhaustion, driving ovarian failure. However, a growing body of evidence, including the isolation of germline stem cells (GSC) from adult mouse ovaries that produce developmentally-competent oocytes, has challenged this belief. In addition, rare germline stem-like cells capable of generating oocytes in vitro that undergo parthenogenesis to form blastocyst-like structures have recently been identified in postmenopausal human ovaries. Here we show that the germline-specific meiosis-commitment genes,Stimulated by retinoic acid gene 8 (Stra8) and Deleted in azoospermia-like (Dazl), are highly expressed in aged mouse ovaries. However, histological and marker analyses fail to demonstrate the presence of oocytes, supporting that Stra8 and Dazl are expressed in premeiotic germ cells that do not undergo further differentiation. Through the use of aged germline-specific GFP-expressing transgenic mice, we further show that these germ cells can generate GFP-positive oocytes that co-express the primordial oocyte marker NOBOX and form follicles when grafted into young adult wild-type female hosts. Thus, aged mouse ovaries possess a rare population of premeiotic germ cells that retain the capacity to form oocytes if exposed to a young host environment.
在人体所有主要器官系统中，女性的卵巢是随着年龄增长最早出现功能受损的器官。直到最近，传统观点认为雌性哺乳动物在出生时就拥有一批不可再生的含卵母细胞卵泡池，这些卵泡在出生后的生命过程中逐渐耗尽直至枯竭，从而导致卵巢功能衰竭。然而，越来越多的证据，包括从成年小鼠卵巢中分离出能产生具有发育能力卵母细胞的生殖系干细胞（GSC），对这一观点提出了挑战。此外，最近在绝经后人类卵巢中发现了罕见的能够在体外产生卵母细胞并进行孤雌生殖形成囊胚样结构的生殖系干细胞样细胞。在此，我们表明生殖系特异性减数分裂承诺基因，即视黄酸刺激基因8（Stra8）和无精子症样缺失基因（Dazl），在老年小鼠卵巢中高度表达。然而，组织学和标志物分析未能证明卵母细胞的存在，这支持了Stra8和Dazl在未进一步分化的减数分裂前生殖细胞中表达。通过使用老年生殖系特异性绿色荧光蛋白表达转基因小鼠，我们进一步表明，当将这些生殖细胞移植到年轻成年野生型雌性宿主中时，它们可以产生共表达原始卵母细胞标志物NOBOX的绿色荧光蛋白阳性卵母细胞并形成卵泡。因此，老年小鼠卵巢中存在罕见的减数分裂前生殖细胞群体，如果暴露于年轻宿主环境中，这些细胞保留形成卵母细胞的能力。
