RUDN University, 117198 Moscow, Russia.
Research Institute of Experimental Biology and Medicine, Burdenko Voronezh State Medical University, 394036 Voronezh, Russia.
Cells. 2024 May 14;13(10):833. doi: 10.3390/cells13100833.
Infertility is an important personal and society disease, of which the male factor represents half of all causes. One of the aspects less studied in male infertility is the immunological testicular microenvironment. Mast cells (MCs), having high potential for regulating spermatogenesis due to fine-tuning the state of the integrative buffer metabolic environment, are one of the most crucial cellular subpopulations of the testicular interstitium. One important component of the MC secretome is proteases that can act as proinflammatory agents and in extracellular matrix (ECM) remodeling. In the testis, MCs are an important cell component of the testicular interstitial tissue (TIT). However, there are still no studies addressing the analysis of a specific MC protease-carboxypeptidase A3 (CPA3)-in cases with altered spermatogenesis. The cytological and histotopographic features of testicular CPA3+ MCs were examined in a study involving 34 men with azoospermia. As revealed, in cases with non-obstructive azoospermia, a higher content of CPA3+ MCs in the TIT and migration to the microvasculature and peritubular tissue of seminiferous tubules were observed when compared with cases with obstructive azoospermia. Additionally, a high frequency of CPA3+ MCs colocalization with fibroblasts, Leydig cells, and elastic fibers was detected in cases with NOA. Thus, CPA3 seems to be of crucial pathogenetic significance in the formation of a profibrogenic background of the tissue microenvironment, which may have direct and indirect effects on spermatogenesis.
不育症是一种重要的个人和社会疾病,其中男性因素占所有病因的一半。男性不育症中研究较少的一个方面是免疫性睾丸微环境。肥大细胞(MCs)由于精细调节整合缓冲代谢环境的状态,具有调节精子发生的巨大潜力,是睾丸间质中最重要的细胞亚群之一。MC 分泌组的一个重要组成部分是蛋白酶,它可以作为促炎剂和细胞外基质(ECM)重塑剂。在睾丸中,MC 是睾丸间质组织(TIT)的重要细胞成分。然而,目前仍没有研究分析在精子发生改变的情况下特定的 MC 蛋白酶-羧肽酶 A3(CPA3)。在一项涉及 34 名无精子症男性的研究中,研究了睾丸 CPA3+MC 的细胞学和组织拓扑特征。结果显示,在非阻塞性无精子症病例中,与阻塞性无精子症病例相比,TIT 中 CPA3+MC 的含量更高,并且向微脉管系统和生精小管周围组织迁移。此外,在非阻塞性无精子症病例中,CPA3+MC 与成纤维细胞、Leydig 细胞和弹性纤维的共定位频率较高。因此,CPA3 似乎在组织微环境的纤维生成背景形成中具有关键的发病意义,这可能对精子发生有直接和间接的影响。