Department of Obstetrics, Gynecology and Reproduction, Université Laval, Quebec, Canada.
Hum Reprod Update. 2021 Dec 21;28(1):51-66. doi: 10.1093/humupd/dmab029.
Spermatozoa acquire their motility and fertilizing abilities during their maturation through the epididymis. This process is controlled by epididymal epithelial cells that possess features adapted to sense and respond to their surrounding environment and to communicate with spermatozoa. During the past decade, new intercellular communication processes have been discovered, including the secretion and transport of molecules from the epithelium to spermatozoa via extracellular vesicles (EVs), as well as sensing of the intraluminal milieu by cellular extensions.
This review addresses recent findings regarding epididymal epithelial cell features and interactions between spermatozoa and the epididymal epithelium as well as epigenetic modifications undergone by spermatozoa during transit through the epididymal microenvironment.
A systematic search was conducted in Pubmed with the keyword 'epididymis'. Results were filtered on original research articles published from 2009 to 2021 and written in the English language. One hundred fifteen original articles presenting recent advancements on the epididymis contribution to sperm maturation were selected. Some additional papers cited in the primary reference were also included. A special focus was given to higher mammalian species, particularly rodents, bovines and humans, that are the most studied in this field.
This review provides novel insights into the contribution of epididymal epithelium and EVs to post-testicular sperm maturation. First, new immune cell populations have been described in the epididymis, where they are proposed to play a role in protecting the environment surrounding sperm against infections or autoimmune responses. Second, novel epididymal cell extensions, including dendrites, axopodia and primary cilia, have been identified as sensors of the environment surrounding sperm. Third, new functions have been outlined for epididymal EVs, which modify the sperm epigenetic profile and participate in transgenerational epigenetic inheritance of paternal traits.
Although the majority of these findings result from studies in rodents, this fundamental research will ultimately improve our knowledge of human reproductive physiopathologies. Recent discoveries linking sperm epigenetic modifications with paternal environmental exposure and progeny outcome further stress the importance of advancing fundamental research on the epididymis. From this, new therapeutic options for infertile couples and better counseling strategies may arise to increase positive health outcomes in children conceived either naturally or with ART.
精子在通过附睾的过程中获得运动能力和受精能力。这个过程受附睾上皮细胞控制，这些细胞具有适应感知和响应周围环境以及与精子相互作用的特征。在过去的十年中，已经发现了新的细胞间通讯过程，包括上皮细胞将分子分泌和运输到精子中的过程，以及细胞突起对管腔内环境的感应。
本综述讨论了最近关于附睾上皮细胞特征以及精子和附睾上皮之间相互作用的发现，以及精子在通过附睾微环境时经历的表观遗传修饰。
在 Pubmed 上使用关键字“epididymis”进行了系统搜索。结果根据 2009 年至 2021 年发表的原始研究文章进行了过滤，并且这些文章使用英语书写。选择了 115 篇介绍附睾对精子成熟贡献的最新进展的原始文章。也包括了一些在主要参考文献中引用的额外论文。特别关注了在该领域研究最多的高等哺乳动物物种，特别是啮齿动物、牛和人类。
本综述提供了关于附睾上皮和 EVs 对精子后熟的贡献的新见解。首先，在附睾中已经描述了新的免疫细胞群体，它们被提议在保护精子周围的环境免受感染或自身免疫反应方面发挥作用。其次，已经鉴定出附睾新的细胞突起，包括树突、轴突和初级纤毛，作为精子周围环境的传感器。第三，已经概述了附睾 EVs 的新功能，它们修饰精子的表观遗传特征，并参与父系性状的跨代表观遗传遗传。
尽管这些发现主要来自于对啮齿动物的研究，但这项基础研究最终将提高我们对人类生殖生理学病理学的认识。最近的发现将精子表观遗传修饰与父系环境暴露和后代结果联系起来，进一步强调了推进对附睾的基础研究的重要性。由此，可以为不孕夫妇提供新的治疗选择，并制定更好的咨询策略，以增加自然或通过 ART 受孕的儿童的积极健康结果。
