Manfrevola Francesco, Mosca Nicola, Mele Vincenza Grazia, Chioccarelli Teresa, Migliaccio Antonella, Mattia Monica, Pezzullo Mariaceleste, Cobellis Gilda, Potenza Nicoletta, Chianese Rosanna
Department of Experimental Medicine, University of Campania "Luigi Vanvitelli", 80138 Naples, Italy.
Department of Environmental, Biological and Pharmaceutical Science and Technologies, University of Campania "Luigi Vanvitelli", 81100 Caserta, Italy.
Int J Mol Sci. 2025 Mar 14;26(6):2614. doi: 10.3390/ijms26062614.
The epididymis represents a pivotal organ for sperm maturation and male fertility maintenance. During the epididymal journey, sperm cells undergo morphological and molecular changes that need to acquire the morpho-functional skills necessary for successful oocyte fertilization. Not last, a great enrichment of the spermatozoa RNA payload occurs via an epithelium-derived epididymosome transfer. Currently, circular RNAs (circRNAs), a class of non-coding RNAs (ncRNAs), are acquiring a prominent role in the setting of sperm quality parameters. In this regard, they are considered potential targets in several male infertility conditions. Despite their consolidated role, few notions are known regarding the alleged epididymal backsplicing activity. In the current review, we discuss the main aspects of spermatozoa maturation along the epididymis and the circRNA role in the field of male reproduction. We also report the most recent findings on the circRNA biogenesis that occurs in the epididymal duct, providing new fascinating evidence on epididymal-derived circRNAs. Finally, we show preliminary compelling data on epididymal backsplicing by exploiting the experimental mouse model of aging. Collectively, these data evidence a remarkable role of the epididymis in remodeling the circRNA payload and in shaping its profile in maturating spermatozoa.
附睾是精子成熟和维持男性生育能力的关键器官。在附睾行程中，精子细胞会经历形态和分子变化，以获得成功使卵母细胞受精所需的形态功能技能。最后，通过上皮来源的附睾外泌体转移，精子RNA有效载荷会大量富集。目前，环状RNA（circRNAs）作为一类非编码RNA（ncRNAs），在精子质量参数的设定中正发挥着重要作用。在这方面，它们被认为是几种男性不育症的潜在靶点。尽管它们的作用已得到确认，但关于所谓的附睾反向剪接活性，人们所知甚少。在本综述中，我们讨论了精子在附睾中成熟的主要方面以及circRNA在男性生殖领域的作用。我们还报告了附睾管中发生的circRNA生物合成的最新发现，为附睾来源的circRNAs提供了新的有趣证据。最后，我们通过利用衰老实验小鼠模型展示了关于附睾反向剪接的初步有力数据。总体而言，这些数据证明了附睾在重塑circRNA有效载荷以及在成熟精子中塑造其特征方面的显著作用。
