The Second Affiliated Hospital and Yuying Children's Hospital, Wenzhou Medical University, Wenzhou, China.
The Mary M. Wohlford Laboratory for Male Contraceptive Research, Center for Biomedical Research, Population Council, New York, NY, USA.
Crit Rev Biochem Mol Biol. 2021 Jun;56(3):236-254. doi: 10.1080/10409238.2021.1901255. Epub 2021 Mar 25.
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.
自发现下丘脑-垂体-睾丸轴以来，已经过去了近五十年。这条轴是指连接下丘脑、垂体和睾丸的激素轴，它通过生精小管中的精子发生来调节精子的产生，以及间质中的莱迪希细胞通过类固醇生成来调节睾丸中的睾酮产生。新出现的证据表明，在生精上皮内存在一个调节网络，利用上皮内特定区域产生的生物活性分子。研究表明，生物活性片段是由基膜中的结构层粘连蛋白和胶原链产生的。此外，生物活性肽也在生精上皮中 Sertoli-精子细胞界面的非基底层粘连蛋白链上局部产生，称为顶外质特化（顶 ES，一种睾丸特异性基于肌动蛋白的锚定连接类型）。这些生物活性肽是通过基质金属蛋白酶（MMPs）的蛋白水解切割从相应部位的结构层粘连蛋白和/或胶原中产生的。反过来，它们通过连接顶区和基底区、顶 ES、血睾屏障（BTB）和固有膜的基底层，作为自分泌和/或旁分泌因子来调节和协调上皮内的细胞事件。这些生物活性肽/片段支持的细胞事件包括精子发生时精子的释放、重塑免疫屏障以促进前细线期精母细胞穿过 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支持精子发生的局部调节生物分子网络的生物学的急需理解。
