Abstract
Despite advances in assisted reproductive technologies, infertility remains a consistent health problem worldwide. Spermiation is the process through which mature spermatids detach from the supporting Sertoli cells and are released into the tubule lumen. Spermiation failure leads to lack of mature spermatozoa and, if not occasional, could result into azoospermia, major cause of male infertility in human population. Spermatids are led through their differentiation into spermatozoa by the apical ectoplasmic specialization (aES), a testis-specific, actin-based anchoring junction restricted to the Sertoli-spermatid interface. The aES helps spermatid movement across the seminiferous epithelium, promotes spermatid positioning, and prevents the release of immature spermatozoa. To accomplish its functions, aES needs to undergo tightly and timely regulated restructuring. Even if components of aES are partly known, the mechanism/s through which aES is regulated remains still elusive. In this review, we propose a model by which the small GTPase Rap1 could regulate aES assembly/remodelling. The characterization of key players in the dynamic of aES, such as Rap1, could open new possibility to develop prognostic, diagnostic, and therapeutic approaches for male patients under treatment for infertility as well as it could lead to the identification of new target for male contraception.
Highlights
IntroductionSpermatogenesis is a very complex and regulated process during which the diploid spermatogonia divide and differentiate into haploid spermatozoa [1,2,3,4]
Spermatogenesis is a very complex and regulated process during which the diploid spermatogonia divide and differentiate into haploid spermatozoa [1,2,3,4].The correct development of fertile spermatozoa relies on the peculiar organization of the seminiferous epithelium
It is clear that germ cells have to remain anchored to Sertoli cells till the final steps in order to avoid a premature release as immature spermatids, with consequence on the male fertility potential (Figure 1)
Summary
Spermatogenesis is a very complex and regulated process during which the diploid spermatogonia divide and differentiate into haploid spermatozoa [1,2,3,4]. The germ cells at different stages of differentiation display a unique pattern of association with Sertoli cells which can be classified into twelve stages (from I to XII) [1, 2, 4]. The BTB physically divides the seminiferous epithelium in two compartments, that is, a basal compartment where spermatogonia and spermatocytes reside, and an adluminal compartment where spermatids differentiate to develop into spermatozoa (Figure 1) [16, 17]. The molecular components and the functions of the BTB have been extensively reviewed (for excellent reviews, see [12, 17, 21]); it will be no longer discussed here This brief review will focus around the apical ES (aES), restricted to Sertoli-postmeiotic germ cells at the adluminal compartment. From bES, aES does not coexist with other junctions: the aES is the only junctional device that sustains the association between Sertoli and elongating/elongated spermatids (from step 8 of differentiation) until the early phase of spermiation when it disassembles (Figure 1) [13, 22,23,24]
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