Laboratoire d'Andrologie, Pôle de Recherche en Physiologie de la Reproduction, Institut de Recherche Expérimentale et Clinique (IREC), Université Catholique de Louvain, 1200 Brussels, Belgium.
Department of Gynecology-Andrology, Cliniques Universitaires Saint-Luc, 1200 Brussels, Belgium.
Int J Mol Sci. 2024 Jun 25;25(13):6925. doi: 10.3390/ijms25136925.
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 A and A 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.
体外成熟 (IVM) 是一种有前途的生育力恢复策略，适用于非梗阻性无精子症患者或青春期前男孩获取具有受精能力的精子。然而，人类未成熟睾丸组织的体外精子发生仍未实现。了解不同发育阶段的各种人类睾丸转录谱有助于我们更好地理解睾丸发育。本范围综述旨在描述从胎儿期到成年期的睾丸发育和成熟，并寻找信息来优化 IVM。确定并批判性地回顾了与天然和体外培养的人类睾丸细胞以及单细胞 RNA 测序 (scRNA-seq) 相关的研究论文。特别关注基因本体术语，以方便解释相关基因的生物学功能。描述了生殖细胞和体细胞谱系的不同连续成熟状态。scRNA-seq 通常在 11 岁左右显示出主要的变化，最终达到成年状态。描述了不同的精原干细胞 (SSC) 亚状态，scRNA-seq 分析有利于范式转变，因为 A 和 A 精原细胞群体在不同的 SSC 状态中不能明显区分。体细胞谱系的数据有限，尤其是支持细胞，因为与细胞大小相关的技术问题。在细胞培养过程中，scRNA-seq 数据表明，在 AKT 信号通路抑制剂存在的情况下，未分化的 SSCs 更受青睐。氧化磷酸化途径的参与取决于细胞的成熟状态。在睾丸发育和成熟过程中共同鉴定的细胞信号通路突出了在 IVM 特定成熟阶段可能至关重要的因素。
