Begum S, Papaioannou V E, Gosden R G
Department of Genetics and Development, College of Physicians and Surgeons of Columbia University, New York, NY 10032, USA.
Hum Reprod. 2008 Oct;23(10):2326-30. doi: 10.1093/humrep/den249. Epub 2008 Jul 1.
According to conventional theory, the oocyte population is not renewed in mammalian ovaries after birth. A new hypothesis proposes that oocytes are generated continuously from haematopoietic progenitor cells. There is, however, no evidence that they can ovulate, although they may partially restore fertility by organizing 'helper follicles'. The hypothesis that follicles can form de novo in adult ovaries has been tested in a transplant model.
Ovaries from adult mice were transplanted under the kidney capsule or into the ovarian bursa of histocompatible, transgenic CAG::H2B-EGFP host animals. Some donors were sterilized before transplantation by X-irradiation to ensure 'empty niches' were available for repopulation. The phenotype of follicular oocytes at 2, 4 and 8 weeks post-transplantation was scored by epifluorescence.
A total of 819 oocytes were examined in 30 ovarian grafts. None expressed green fluorescence, as would be predicted if they had formed de novo from germ cell progenitors in the systemic circulation of the host. Furthermore, small follicles eliminated by irradiation were not replaced in transplanted ovaries, and the few growing follicles present were apparently survivors of the original population.
No evidence was found to support the hypothesis that progenitor cells from extra-ovarian sources can repopulate the adult ovary. The findings are consistent with the conventional view that a limited number of oocytes are formed before birth and declines with age. The study did not, however, rule out the possibility that germline stem cells may reside in the adult ovary.
根据传统理论,哺乳动物出生后卵巢中的卵母细胞群体不会更新。一种新的假说提出,卵母细胞是由造血祖细胞持续产生的。然而,没有证据表明它们能够排卵,尽管它们可能通过组织“辅助卵泡”部分恢复生育能力。卵泡可在成年卵巢中重新形成的假说已在移植模型中得到验证。
将成年小鼠的卵巢移植到组织相容性转基因CAG::H2B-EGFP宿主动物的肾包膜下或卵巢囊中。一些供体在移植前通过X射线照射进行绝育,以确保有“空龛”可供重新填充。通过落射荧光对移植后2周、4周和8周时卵泡卵母细胞的表型进行评分。
在30个卵巢移植物中总共检查了819个卵母细胞。没有一个表达绿色荧光,而如果它们是由宿主全身循环中的生殖细胞祖细胞重新形成的话,就会出现这种情况。此外,移植卵巢中经照射消除的小卵泡没有被替代,少数生长中的卵泡显然是原始卵泡群体的幸存者。
没有发现证据支持卵巢外来源的祖细胞可以重新填充成年卵巢这一假说。这些发现与传统观点一致,即出生前形成数量有限的卵母细胞,并随年龄增长而减少。然而,该研究并未排除生殖系干细胞可能存在于成年卵巢中的可能性。