State Key Laboratory of Medicinal Chemical Biology, The 2011 Collaborative Innovation Center of Tianjin for Medical Epigenetics and College of Life Sciences, Nankai University, Tianjin, China; Key Laboratory of Ministry of Health on Hormones and Development, Metabolic Diseases Hospital, Tianjin Medical University, Tianjin, China.
Stem Cells. 2013 Nov;31(11):2538-50. doi: 10.1002/stem.1480.
Female germline or oogonial stem cells transiently residing in fetal ovaries are analogous to the spermatogonial stem cells or germline stem cells (GSCs) in adult testes where GSCs and meiosis continuously renew. Oocytes can be generated in vitro from embryonic stem cells and induced pluripotent stem cells, but the existence of GSCs and neo-oogenesis in adult mammalian ovaries is less clear. Preliminary findings of GSCs and neo-oogenesis in mice and humans have not been consistently reproducible. Monkeys provide the most relevant model of human ovarian biology. We searched for GSCs and neo-meiosis in ovaries of adult monkeys at various ages, and compared them with GSCs from adult monkey testis, which are characterized by cytoplasmic staining for the germ cell marker DAZL and nuclear expression of the proliferative markers PCNA and KI67, and pluripotency-associated genes LIN28 and SOX2, and lack of nuclear LAMIN A, a marker for cell differentiation. Early meiocytes undergo homologous pairing at prophase I distinguished by synaptonemal complex lateral filaments with telomere perinuclear distribution. By exhaustive searching using comprehensive experimental approaches, we show that proliferative GSCs and neo-meiocytes by these specific criteria were undetectable in adult mouse and monkey ovaries. However, we found proliferative nongermline somatic stem cells that do not express LAMIN A and germ cell markers in the adult ovaries, notably in the cortex and granulosa cells of growing follicles. These data support the paradigm that adult ovaries do not undergo germ cell renewal, which may contribute significantly to ovarian senescence that occurs with age.
女性生殖系或卵原干细胞短暂存在于胎儿卵巢中，类似于成人睾丸中的精原干细胞或生殖干细胞（GSCs），其中 GSCs 和减数分裂持续更新。卵母细胞可以从胚胎干细胞和诱导多能干细胞体外产生，但成年哺乳动物卵巢中 GSCs 和新卵发生的存在尚不清楚。在小鼠和人类中 GSCs 和新卵发生的初步发现尚未得到一致的重现。猴子提供了最相关的人类卵巢生物学模型。我们在不同年龄的成年猴子的卵巢中寻找 GSCs 和新减数分裂，并将其与成年猴子睾丸中的 GSCs 进行比较，后者的特征是细胞质中存在生殖细胞标记物 DAZL 和增殖标记物 PCNA 和 KI67 的核表达，以及多能相关基因 LIN28 和 SOX2，并且缺乏核 LAMIN A，这是细胞分化的标志物。早期减数分裂在前期经历同源配对，特征是联会复合体侧丝与端粒核周分布。通过使用全面的实验方法进行详尽搜索，我们表明，增殖的 GSCs 和新减数分裂细胞不能用这些特定标准在成年小鼠和猴子的卵巢中检测到。然而，我们发现了增殖的非生殖系体细胞干细胞，它们在成年卵巢中不表达 LAMIN A 和生殖细胞标记物，特别是在生长卵泡的皮质和颗粒细胞中。这些数据支持成年卵巢不进行生殖细胞更新的范例，这可能对与年龄相关的卵巢衰老有重要贡献。
