Virant-Klun Irma
Department of Obstetrics and Gynaecology, University Medical Center Ljubljana, Ljubljana, Slovenia.
Stem Cells Cloning. 2015 Mar 20;8:49-60. doi: 10.2147/SCCAA.S32650. eCollection 2015.
In spite of generally accepted dogma that the total number of follicles and oocytes is established in human ovaries during the fetal period of life rather than forming de novo in adult ovaries, some new evidence in the field challenges this understanding. Several studies have shown that different populations of stem cells, such as germinal stem cells and small round stem cells with diameters of 2 to 4 μm, that resembled very small embryonic-like stem cells and expressed several genes related to primordial germ cells, pluripotency, and germinal lineage are present in adult human ovaries and originate in ovarian surface epithelium. These small stem cells were pushed into the germinal direction of development and formed primitive oocyte-like cells in vitro. Moreover, oocyte-like cells were also formed in vitro from embryonic stem cells and induced pluripotent stem cells. This indicates that postnatal oogenesis is not excluded. It is further supported by the occurrence of mesenchymal stem cells that can restore the function of sterilized ovaries and lead to the formation of new follicles and oocytes in animal models. Both oogenesis in vitro and transplantation of stem cell-derived "oocytes" into the ovarian niche to direct their natural maturation represent a big challenge for reproductive biomedicine in the treatment of female infertility in the future and needs to be explored and interpreted with caution, but it is still very important for clinical practice in the field of reproductive medicine.
尽管普遍接受的教条认为,人类卵巢中卵泡和卵母细胞的总数在胎儿期就已确定,而非在成年卵巢中重新形成,但该领域的一些新证据对这一认识提出了挑战。多项研究表明,成年人类卵巢中存在不同类型的干细胞,如生殖干细胞和直径为2至4微米的小圆形干细胞,它们类似于非常小的胚胎样干细胞,并表达了一些与原始生殖细胞、多能性和生殖谱系相关的基因,且起源于卵巢表面上皮。这些小干细胞被推向生殖发育方向,并在体外形成原始卵母细胞样细胞。此外,胚胎干细胞和诱导多能干细胞在体外也能形成卵母细胞样细胞。这表明出生后的卵子发生并非不可能。动物模型中能恢复绝育卵巢功能并导致新卵泡和卵母细胞形成的间充质干细胞的出现进一步支持了这一点。体外卵子发生以及将干细胞衍生的“卵母细胞”移植到卵巢微环境中以引导其自然成熟,对于未来生殖生物医学治疗女性不孕症而言都是巨大挑战,需要谨慎探索和解读,但对生殖医学领域的临床实践仍非常重要。