RIKEN BioResouce Center, Tsukuba, Ibaraki, Japan.
Biol Reprod. 2011 Apr;84(4):631-8. doi: 10.1095/biolreprod.110.087122. Epub 2010 Nov 10.
Primordial germ cells (PGCs) are undifferentiated germ cells in developing fetuses. As these cells give rise to definitive oocytes and spermatozoa that contribute to new life in the next generation, their development must be under strict control, regarding genetic and epigenetic aspects. However, we do not know to what extent their development depends on the specific milieu. In this study, we transplanted mouse PGCs collected from male and female gonads at 12.5 days postcoitum, together with gonadal somatic cells, under kidney capsules of adult mice. The transplanted PGC and gonadal somatic cells constructed testis-like and ovary-like tissues, respectively, under the kidney capsules within 4 wk. Normal-appearing round spermatids and fully grown germinal vesicle (GV) oocytes developed within these tissues. Ectopic spermatogenesis continued thereafter, while oogenesis consisted of only a single wave. The injection of these round spermatids directly into mature in vivo-derived oocytes led to the birth at term of normal pups. PGC-derived GV oocytes were isolated, induced to mature in vitro, and injected with normal spermatozoa. The injected oocytes were successfully fertilized and developed into normal pups. Our findings demonstrate the remarkable flexibility of PGC development, which can proceed up to the functional gamete stage under spatially and temporally noninnate conditions. This transplantation system may provide a unique technical basis for induction of the development of early germ cells of exogenous origins, such as those from embryonic stem cells.
原始生殖细胞(PGC)是发育中胎儿中未分化的生殖细胞。由于这些细胞产生了新生命中至关重要的卵母细胞和精子,因此它们的发育必须受到严格控制,包括遗传和表观遗传方面。然而,我们不知道它们的发育在多大程度上依赖于特定的环境。在这项研究中,我们将从受精后 12.5 天的雄性和雌性性腺中收集的小鼠 PGC 与性腺体细胞一起移植到成年小鼠的肾脏包膜下。移植的 PGC 和性腺体细胞在 4 周内分别构建了睾丸样和卵巢样组织。这些组织中发育出了外观正常的圆形精子和完全成熟的生发泡(GV)卵母细胞。此后,异位精子发生继续进行,而卵子发生仅发生一次。将这些圆形精子直接注射到成熟的体内来源的卵母细胞中,导致正常幼仔足月出生。从 PGC 衍生的 GV 卵母细胞被分离出来,在体外诱导成熟,并注入正常精子。注射的卵母细胞成功受精并发育成正常幼仔。我们的发现表明 PGC 发育具有显著的灵活性,可以在非固有空间和时间条件下达到功能配子阶段。这种移植系统可能为诱导外源来源的早期生殖细胞的发育提供独特的技术基础,例如胚胎干细胞。