Gladstone Institute of Cardiovascular Disease, San Francisco, California 94158, USA.
Fertil Steril. 2012 Jun;97(6):1250-9. doi: 10.1016/j.fertnstert.2012.04.037.
Infertility caused by the disruption or absence of germ cells (i.e., sperm or egg) is a major and largely incurable medical problem. In vitro disease modeling using normal human germline cells is required to better understand the precise molecular mechanisms of infertility and to develop drugs to treat this condition. Recent advances in the differentiation methods of embryonic stem cells (ESCs) provide new avenues to generate germ cells in vitro. Furthermore, the discovery that induced pluripotent stem cells (iPSCs) can be created from a patient's adult somatic cells by introducing the combinations of several transcription factors (e.g., OCT3/4, SOX2, KLF4, and MYC) enables us to generate new and powerful in vitro human disease models. In this review, we summarize recent advances in the development of human germ cells from in vivo and in vitro cultured ESCs/iPSCs. Based on these studies, we propose strategies to develop in vitro disease models of infertility using human ESCs/iPSCs. Then, we also discuss the challenges that need to be addressed to harness the full potential of these models. These models will enable us to understand the precise molecular pathologies of infertility and will aid in the development of new treatments.
由生殖细胞（即精子或卵子）的破坏或缺失引起的不育是一个主要的、在很大程度上无法治愈的医学问题。使用正常的人类生殖细胞进行体外疾病建模对于更好地理解不育的确切分子机制以及开发治疗这种疾病的药物是必要的。胚胎干细胞（ESCs）分化方法的最新进展为体外生成生殖细胞提供了新的途径。此外，通过引入几种转录因子（如 OCT3/4、SOX2、KLF4 和 MYC），可以从患者的成体细胞中诱导产生多能干细胞（iPSCs），这一发现使我们能够生成新的、强大的体外人类疾病模型。在这篇综述中，我们总结了从体内和体外培养的 ESCs/iPSCs 中开发人类生殖细胞的最新进展。基于这些研究，我们提出了使用人类 ESCs/iPSCs 开发不育症体外疾病模型的策略。然后，我们还讨论了利用这些模型需要解决的挑战。这些模型将使我们能够了解不育的确切分子病理学，并有助于开发新的治疗方法。
