The potential of sertoli cells (SCs) derived exosomes and its therapeutic efficacy in male reproductive disorders

Abstract

In the male reproductive system, seminiferous tubules in testis are lined by a complex stratified epithelium containing two distinct populations of cells, spermatogenic cells that develop into spermatozoa, and sertoli cells (SCs) that mainly support and nourish spermatogenic cell lineage as well as exerting powerful effect on men reproductive capacity. Different varieties of proteins, hormones, exosomes and growth factors are secreted by SCs. There are different kinds of junctions found between SCs called BTB. It was elucidated that complete absence of BTB or its dysfunction leads to infertility. To promote spermatogenesis, crosstalk of SCs with spermatogenic cells plays an important role. The ability of SCs to support germ cell productivity and development is related to its various products carrying out several functions. Exosomes (EXOs) are one of the main EVs with 30-100 nm size generating from endocytic pathway. They are produced in different parts of male reproductive system including epididymis, prostate and SCs. The most prominent characteristics of SC-based exosomes is considered mutual interaction of sertoli cells with spermatogonial stem cells and Leydig cells mainly through establishment of intercellular communication. Exosomes have gotten a lot of interest because of their role in pathobiological processes and as a cell free therapy which led to developing multiple exosome isolation methods based on different principles. Transmission of nucleic acids, proteins, and growth factors via SC-based exosomes and exosomal miRNAs are proved to have potential to be valuable biomarkers in male reproductive disease. Among testicular abnormalities, non-obstructive azoospermia and testicular cancer have been more contributed with SCs performance. The identification of key proteins and miRNAs involved in the signaling pathways related with spermatogenesis, can serve as diagnostic and regenerative targets in male infertility.

Keywords: Azoospermia; Blood testis barrier; Exosome therapy; Male reproductive disease; Sertoli cells; miRNA.