Transplantation directs oocyte maturation from embryonic stem cells and provides a therapeutic strategy for female infertility.
Transplantation directs oocyte maturation from embryonic stem cells and provides a therapeutic strategy for female infertility.
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DOI：
10.1093/hmg/ddp393
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发表时间：
2009-11-15
影响因子：
3.5
通讯作者：
Reijo Pera RA
中科院分区：
文献类型：
--
作者：
Nicholas CR;Haston KM;Grewall AK;Longacre TA;Reijo Pera RA
10% - 15%的夫妇不育，最常见的原因与产生很少或不产生卵母细胞或精子有关。然而，我们对人类生殖细胞发育的了解甚少，这至少部分是由于早期阶段难以进行基因和发育研究。胚胎干细胞（ESCs）提供了一个体外系统来研究卵母细胞发育，并有可能治疗女性不育症。然而，大多数关于胚胎干细胞向卵母细胞分化的研究没有记录内源性发育的基本特性，这使得很难确定分化的生殖细胞的生理相关性。在此，我们试图确定胚胎干细胞分化过程中卵母细胞发育的基本参数，以便在将其应用于人类系统之前，以小鼠为模型探索其在基础发育遗传学应用中的适用性。我们通过单细胞表达谱分析以及对包括对特定成熟培养基的反应性、Dazl的共同基因需求以及进入减数分裂等功能节点的分析，展示了胚胎干细胞在体外确定性生殖细胞分化的时间线，该时间线最初与体内内源性卵母细胞发育相似。然而，胚胎干细胞衍生的卵母细胞在体外最终无法成熟。为了克服这一障碍，我们将胚胎干细胞衍生的卵母细胞移植到卵巢微环境中以引导其功能成熟，从而为卵母细胞的生理相关性提供了有力证据，并为不育症提供了一种潜在的治疗策略。
Ten to 15% of couples are infertile, with the most common causes being linked to the production of few or no oocytes or sperm. Yet, our understanding of human germ cell development is poor, at least in part due to the inaccessibility of early stages to genetic and developmental studies. Embryonic stem cells (ESCs) provide an in vitro system to study oocyte development and potentially treat female infertility. However, most studies of ESC differentiation to oocytes have not documented fundamental properties of endogenous development, making it difficult to determine the physiologic relevance of differentiated germ cells. Here, we sought to establish fundamental parameters of oocyte development during ESC differentiation to explore suitability for basic developmental genetic applications using the mouse as a model prior to translating to the human system. We demonstrate a timeline of definitive germ cell differentiation from ESCs in vitro that initially parallels endogenous oocyte development in vivo by single-cell expression profiling and analysis of functional milestones including responsiveness to defined maturation media, shared genetic requirement of Dazl, and entry into meiosis. However, ESC-derived oocyte maturation ultimately fails in vitro. To overcome this obstacle, we transplant ESC-derived oocytes into an ovarian niche to direct their functional maturation and, thereby, present rigorous evidence of oocyte physiologic relevance and a potential therapeutic strategy for infertility.
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影响因子：
2.7
作者：
Farini, D;Scaldaferri, ML;De Felici, M
通讯作者：
De Felici, M
影响因子：
5.2
作者：
Bucay, Nathan;Yebra, Mayra;Montgomery, Anthony M. P.
通讯作者：
Montgomery, Anthony M. P.
影响因子：
3.5
作者：
Chassot, Anne-Amandine;Ranc, Fariba;Chaboissier, Marie-Christine
通讯作者：
Chaboissier, Marie-Christine
影响因子：
56.9
作者：
Bowles, J;Knight, D;Koopman, P
通讯作者：
Koopman, P
DOI：
10.1089/clo.2007.0031
发表时间：
2007-12-01
期刊：
CLONING AND STEM CELLS
影响因子：
--
作者：
Kerkis, Alexandre;Fonseca, Simone A. S.;Kerkis, Irina
通讯作者：
Kerkis, Irina