BACKGROUND 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. OBJECTIVE AND RATIONALE 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. SEARCH METHODS 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. OUTCOMES 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. WIDER IMPLICATIONS 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.

中文翻译：

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附睾上皮细胞功能对精子表观遗传变化和后代健康的贡献

背景技术精子在成熟过程中通过附睾获得运动和受精能力。这个过程由附睾上皮细胞控制，这些上皮细胞具有适应感知和响应周围环境并与精子交流的特征。在过去十年中，人们发现了新的细胞间通讯过程，包括分子通过细胞外囊泡 (EV) 从上皮分泌和转运到精子，以及通过细胞延伸感知管腔内环境。目的和基本原理 本综述阐述了关于附睾上皮细胞特征和精子与附睾上皮之间相互作用以及精子在通过附睾微环境的过程中所经历的表观遗传修饰的最新发现。搜索方法 在 Pubmed 中使用关键字“epididymis”进行了系统搜索。结果根据 2009 年至 2021 年发表的以英语撰写的原创研究文章进行筛选。选择了 115 篇原创文章，介绍了附睾对精子成熟的贡献的最新进展。主要参考文献中引用的一些其他论文也包括在内。特别关注高等哺乳动物物种，特别是啮齿动物、牛和人类，这是该领域研究最多的。结果 本综述为附睾上皮和 EV 对睾丸后精子成熟的贡献提供了新的见解。首先，已经在附睾中描述了新的免疫细胞群，它们被提议在保护精子周围环境免受感染或自身免疫反应方面发挥作用。其次，新的附睾细胞延伸，包括树突、轴足和初级纤毛，已被确定为精子周围环境的传感器。第三，附睾 EVs 的新功能已被概述，其修改精子表观遗传谱并参与父系性状的跨代表观遗传。更广泛的影响 虽然这些发现大部分来自啮齿动物研究，但 这项基础研究最终将提高我们对人类生殖生理病理学的认识。最近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的发现进一步强调了推进附睾基础研究的重要性。由此，可能会出现针对不孕夫妇的新治疗选择和更好的咨询策略，以增加自然受孕或接受 ART 受孕的儿童的积极健康结果。