Department of Obstetrics & Gynecology, Medical University of Vienna, Vienna, Austria.
The British Columbia Children's Hospital Research Institute, Vancouver, BC, Canada.
Hum Reprod. 2023 Aug 1;38(8):1449-1463. doi: 10.1093/humrep/dead085.
Research focused on human reproductive biology has primarily relied upon clinical samples affording mainly descriptive studies with limited implementation of functional or mechanistic understanding. More importantly, restricted access to human embryonic material has necessitated the use of animals, primarily rats and mice, and short-term primary cell cultures derived from human patient material. While reproductive developmental processes are generally conserved across mammals, specific features unique to human reproduction have resulted in the development of human-based in vitro systems designed to retain or recapitulate key molecular and cellular processes important in humans. Of note, major advances in 3D epithelial stem cell-based systems modeling human reproductive organ development have been made. These cultures, broadly referred to as organoids, enable research aimed at understanding cellular hierarchies and processes controlling cellular differentiation and function. Moreover, organoids allow the pre-clinical testing of pharmacological substances, both from safety and efficacy standpoints, and hold large potential in driving aspects of personalized medicine that were previously not possible with traditional models. In this mini-review, we focus on summarizing the current state of regenerative organoid culture systems of the female and male reproductive tracts that model organ development, maintenance, and function. Specifically, we will introduce stem cell-based organoid models of the ovary/fallopian tube, endometrium, cervix, prostate gland, and testes. We will also describe organoid systems of the pre-implanting blastocyst and trophoblast, as the blastocyst and its extraembryonic trophectoderm are central to fetal, maternal, and overall pregnancy health. We describe the foundational studies leading to their development and outline the utility as well as specific limitations that are unique and common to many of these in vitro platforms.
研究重点集中在人类生殖生物学上，主要依赖于临床样本，提供的主要是描述性研究，对功能或机制的理解有限。更重要的是，由于胚胎材料获取受限，需要使用动物，主要是大鼠和小鼠，以及源自人类患者材料的短期原代细胞培养物。虽然生殖发育过程在哺乳动物中普遍存在，但人类生殖特有的特定特征导致了开发旨在保留或再现人类中重要的分子和细胞过程的基于人类的体外系统。值得注意的是，基于 3D 上皮干细胞的系统在模拟人类生殖器官发育方面取得了重大进展。这些培养物通常被称为类器官，使旨在理解控制细胞分化和功能的细胞层次结构和过程的研究成为可能。此外，类器官允许对药理学物质进行临床前测试，从安全性和疗效的角度来看，并且具有很大的潜力，可以推动以前使用传统模型无法实现的个性化医学方面的发展。在这篇小型综述中，我们重点总结了女性和男性生殖道的再生类器官培养系统的最新研究进展，这些系统可模拟器官发育、维持和功能。具体来说，我们将介绍基于干细胞的卵巢/输卵管、子宫内膜、子宫颈、前列腺和睾丸的类器官模型。我们还将描述植入前囊胚和滋养层的类器官系统，因为囊胚及其胚胎外滋养层是胎儿、母体和整体妊娠健康的核心。我们将描述导致这些系统发展的基础研究，并概述其独特和常见的用途以及许多这些体外平台所特有的具体局限性。
