Abstract

It is almost five decades since the discovery of the hypothalamic-pituitary-testicular axis. This refers to the hormonal axis that connects the hypothalamus, pituitary gland and testes, which in turn, regulates the production of spermatozoa through spermatogenesis in the seminiferous tubules, and testosterone through steroidogenesis by Leydig cells in the interstitium, of the testes. Emerging evidence has demonstrated the presence of a regulatory network across the seminiferous epithelium utilizing bioactive molecules produced locally at specific domains of the epithelium. Studies have shown that biologically active fragments are produced from structural laminin and collagen chains in the basement membrane. Additionally, bioactive peptides are also produced locally in non-basement membrane laminin chains at the Sertoli-spermatid interface known as apical ectoplasmic specialization (apical ES, a testis-specific actin-based anchoring junction type). These bioactive peptides are derived from structural laminins and/or collagens at the corresponding sites through proteolytic cleavage by matrix metalloproteinases (MMPs). They in turn serve as autocrine and/or paracrine factors to modulate and coordinate cellular events across the epithelium by linking the apical and basal compartments, the apical and basal ES, the blood-testis barrier (BTB), and the basement membrane of the tunica propria. The cellular events supported by these bioactive peptides/fragments include the release of spermatozoa at spermiation, remodeling of the immunological barrier to facilitate the transport of preleptotene spermatocytes across the BTB, and the transport of haploid spermatids across the epithelium to support spermiogenesis. In this review, we critically evaluate these findings. Our goal is to identify research areas that deserve attentions in future years. The proposed research also provides the much needed understanding on the biology of spermatogenesis supported by a local network of regulatory biomolecules.

摘要

下丘脑-垂体-睾丸轴的发现已经过去了将近五年。这是指连接下丘脑、脑垂体和睾丸的激素轴，后者又通过生精小管中的精子发生调节精子的产生，并通过睾丸间质中的 Leydig 细胞通过类固醇生成调节睾酮的产生。新出现的证据表明，利用在上皮特定区域局部产生的生物活性分子，在生精上皮中存在调节网络。研究表明，生物活性片段是由基底膜中的结构层粘连蛋白和胶原链产生的。此外，生物活性肽也在支持 - 精子细胞界面的非基底膜层粘连蛋白链中局部产生，称为顶端外质特化（顶端 ES，一种基于肌动蛋白的睾丸特异性锚定连接类型）。这些生物活性肽来源于相应位点的结构层粘连蛋白和/或胶原蛋白，通过基质金属蛋白酶 (MMP) 的蛋白水解切割。它们反过来作为自分泌和/或旁分泌因子，通过连接顶端和基底隔室、顶端和基底 ES、血睾屏障 (BTB) 和膜的基底膜来调节和协调跨上皮的细胞事件固有的。这些生物活性肽/片段支持的细胞事件包括精子形成时精子的释放，重塑免疫屏障以促进前体精母细胞穿过 BTB 的运输，以及单倍体精子细胞穿过上皮的运输以支持精子发生。在这篇综述中，我们批判性地评估了这些发现。我们的目标是确定未来几年值得关注的研究领域。拟议的研究还提供了对受局部调节生物分子网络支持的精子发生生物学的急需了解。