PDF(Pubmed)
Abstract：
In vitro maturation (IVM) is a promising fertility restoration strategy for patients with nonobstructive azoospermia or for prepubertal boys to obtain fertilizing-competent spermatozoa. However, in vitro spermatogenesis is still not achieved with human immature testicular tissue. Knowledge of various human testicular transcriptional profiles from different developmental periods helps us to better understand the testis development. This scoping review aims to describe the testis development and maturation from the fetal period towards adulthood and to find information to optimize IVM. Research papers related to native and in vitro cultured human testicular cells and single-cell RNA-sequencing (scRNA-seq) were identified and critically reviewed. Special focus was given to gene ontology terms to facilitate the interpretation of the biological function of related genes. The different consecutive maturation states of both the germ and somatic cell lineages were described. ScRNA-seq regularly showed major modifications around 11 years of age to eventually reach the adult state. Different spermatogonial stem cell (SSC) substates were described and scRNA-seq analyses are in favor of a paradigm shift, as the Adark and Apale spermatogonia populations could not distinctly be identified among the different SSC states. Data on the somatic cell lineage are limited, especially for Sertoli cells due technical issues related to cell size. During cell culture, scRNA-seq data showed that undifferentiated SSCs were favored in the presence of an AKT-signaling pathway inhibitor. The involvement of the oxidative phosphorylation pathway depended on the maturational state of the cells. Commonly identified cell signaling pathways during the testis development and maturation highlight factors that can be essential during specific maturation stages in IVM.
摘要：
体外成熟（IVM）是非阻塞性无精子症患者或青春期前男孩获得受精能力精子的有希望的生育能力恢复策略。然而,人未成熟睾丸组织仍未实现体外精子发生。了解不同发育时期的各种人类睾丸转录谱有助于我们更好地了解睾丸发育。本范围审查旨在描述从胎儿期到成年的睾丸发育和成熟，并找到优化IVM的信息。鉴定了与天然和体外培养的人睾丸细胞和单细胞RNA测序（scRNA-seq）相关的研究论文，并进行了严格的审查。特别关注基因本体论术语，以利于解释相关基因的生物学功能。描述了胚芽和体细胞谱系的不同连续成熟状态。ScRNA-seq通常在11岁左右显示出重大变化，最终达到成年状态。描述了不同的精原干细胞（SSC）亚细胞，scRNA-seq分析有利于范式转变，由于在不同的SSC状态中无法明确识别Adark和Apale精原细胞种群。体细胞谱系的数据有限，特别是对于支持细胞，由于与细胞大小有关的技术问题。在细胞培养过程中,scRNA-seq数据显示,在存在AKT信号传导途径抑制剂的情况下,未分化的SSC是有利的。氧化磷酸化途径的参与取决于细胞的成熟状态。睾丸发育和成熟过程中常见的细胞信号传导途径突出了在IVM的特定成熟期可能必不可少的因素。
