When spermatogenesis meets human aging and elevated body mass.
When spermatogenesis meets human aging and elevated body mass.
复制标题
DOI：
10.1093/lifemedi/lnac022
复制
发表时间：
2022-12
期刊：
影响因子：
--
通讯作者：
Guo, Jingtao
中科院分区：
文献类型：
--
作者：
Wang, Xiaoyan;Cairns, Bradley R;Guo, Jingtao
衰老是所有生物体中自然发生的生物过程，影响几乎所有器官和组织类型（包括生殖道）的生理和功能。衰老对生殖的最终影响对于女性和男性来说是不同的：女性在 50 岁左右就会停止月经和排卵，而男性却可以在一生的大部分时间里保持产生精子的能力。生殖干细胞不同的发育轨迹可能导致这种性别差异。具体来说，睾丸中的精原干细胞（SSC）在一生中都保持相对恒定，而男性的生殖干细胞类似SSC不太可能存在于女性的成年卵巢中。有趣的是，尽管许多老年男性的生育能力下降，但根据精子数量衡量，某些人的生育能力相对正常。造成这种异质性的因素可能是由于个体遗传背景的差异和不同的环境暴露造成的。无论如何，了解衰老如何影响男性生育能力需要详细描述潜在的分子机制，并检查生活方式等潜在相关因素的影响，这可能为识别新的治疗靶点或开发有效的干预方案以改善男性的生殖健康提供新途径。睾丸生理学的完整性对于成功的精子发生至关重要，生殖细胞受到睾丸体细胞的支持和指导，包括支持细胞（培育和支持生殖细胞）、间质细胞（产生睾酮）、和睾丸管周细胞（TPC；构成基底膜）。衰老可导致睾丸出现多种生理变化，如纤维化、细胞外基质沉积和基底膜厚度增加[1]。了解这些变化背后的分子机制具有重要的临床和科学意义。最近的工作利用通过快速尸检获得人类睾丸样本的独特途径，利用单细胞转录组分析方法，检查了人类衰老过程中人类睾丸关键成分的变化[2]，揭示了多种改变的途径。其中包括睾丸体细胞中炎症加剧、支持细胞代谢信号失调、Leydig 细胞中刺猬信号和睾酮产生的改变以及 TPC 中的细胞生长不当。此外，虽然年轻的生育男性具有相对一致的分子特征，但在老年男性中观察到了不同程度的上述分子变化，这促使人们进一步研究这些变化的后果。
Aging is a biological process that takes place naturally in all living organisms, and affects the physiology and functionality of almost all organ and tissue types, including the reproductive tracts. The ultimate impact of aging in reproduction differs in women and men: while women stop menstruation and ovulation at the age of around 50, men can maintain the ability to produce sperm for the vast majority of their lifetime. Diverse developmental trajectories of germline stem cells may lead to this difference in genders. Specifically, spermatogonial stem cells (SSCs) in the testis remain relatively constant all life, while germline stem cells analog SSCs in men unlikely exist in the adult ovary of women. Intriguingly, although many older men display declined fertility, certain individuals have relatively normal fertility status, as measured by sperm count. The factors responsible for such heterogeneity may be due to differences in individual genetic background, and diverse environmental exposures. Regardless, understanding how aging affects men’s fertility requires delineation of the detailed underlying molecular mechanisms as well as examination of the influence of potential associated factors such as lifestyle, which may provide new avenue to identify novel therapeutic targets or develop effective intervention options to improve the reproductive health of men.The integrity of testis physiology is critical for successful spermatogenesis, and germline cells are supported and guided by testicular somatic cells, including Sertoli cells (which nurture and support germ cells), Leydig cells (which produce testosterone), and the testicular peritubular cells (TPCs; which contribute to the basement membrane). Aging can lead to several physiological alternations in the testis, such as fibrosis, deposition of extracellular matrix, and increased basement membrane thickness [1]. Understanding the molecular mechanism underlying those changes is of great clinical and scientific significance. Leveraging the unique access to human testis samples through rapid autopsy, recent work took advantage of single cell transcriptomic profiling approach and examined changes in the key components in the human testis during human aging [2], revealing multiple altered pathways. These included elevated inflammation as a globally shared pattern among testicular somatic cells, dysregulated metabolic signaling in Sertoli cells, altered hedgehog signaling and testosterone production in Leydig cells, and improper cell growth in the TPCs. Moreover, while young fertile men share relatively consistent molecular signatures, different degrees of the molecular changes listed above are observed in older men, prompting further investigation into the consequences of those changes.