Crosstalk between Sertoli and Germ Cells in Male Fertility

The testis produces three endogenous regulatory bioactive peptides known as F5-, NC1-, and LG3/4/5-peptide to modulate blood–testis barrier (BTB) and spermatogenic functions. F5- and NC1-peptide promote BTB remodeling by making the barrier ‘leaky’ and facilitate the degeneration of adhesion sites at the Sertoli–spermatid interface known as the apical ectoplasmic specialization (ES), to support the transport of preleptotene spermatocytes across the immunological barrier and the release of sperm at spermiation. LG3/4/5-peptide, however, promotes BTB function by making the barrier ‘tighter’, and promotes spermatid adhesion in the testis. These three bioactive peptides thus serve as molecular switches that can turn various cellular events ‘on’ or ‘off’ during the epithelial cycle of spermatogenesis. Spermatogenesis is supported by intricate crosstalk between Sertoli cells and germ cells including spermatogonia, spermatocytes, haploid spermatids, and spermatozoa, which takes place in the epithelium of seminiferous tubules. Sertoli cells, also known as ‘mother’ or ‘nurse’ cells, provide nutrients, paracrine factors, cytokines, and other biomolecules to support germ cell development. Sertoli cells facilitate the generation of several biologically active peptides, which include F5-, noncollagenous 1 (NC1)-, and laminin globular (LG)3/4/5-peptide, to modulate cellular events across the epithelium. Here, we critically evaluate the involvement of these peptides in facilitating crosstalk between Sertoli and germ cells to support spermatogenesis and thus fertility. Modulating or mimicking the activity of F5-, NC1-, and LG3/4/5-peptide could be used to enhance the transport across the blood–testis barrier (BTB) of contraceptive drugs or to treat male infertility. Spermatogenesis is supported by intricate crosstalk between Sertoli cells and germ cells including spermatogonia, spermatocytes, haploid spermatids, and spermatozoa, which takes place in the epithelium of seminiferous tubules. Sertoli cells, also known as ‘mother’ or ‘nurse’ cells, provide nutrients, paracrine factors, cytokines, and other biomolecules to support germ cell development. Sertoli cells facilitate the generation of several biologically active peptides, which include F5-, noncollagenous 1 (NC1)-, and laminin globular (LG)3/4/5-peptide, to modulate cellular events across the epithelium. Here, we critically evaluate the involvement of these peptides in facilitating crosstalk between Sertoli and germ cells to support spermatogenesis and thus fertility. Modulating or mimicking the activity of F5-, NC1-, and LG3/4/5-peptide could be used to enhance the transport across the blood–testis barrier (BTB) of contraceptive drugs or to treat male infertility. actin-based cell–cell anchoring junction in epithelia or endothelia, usually located behind an actin-based TJ. An AJ is usually created by adhesion protein complexes such as cadherin/catenin and nectin/afadin linked to the actin cytoskeleton. one of the tightest blood–tissue barriers that provides a transcellular and paracellular barrier by restricting the diffusion of water, electrolytes, macromolecules, and biomolecules across the Sertoli cell epithelium to enter the seminiferous epithelium. It comprises TJs, the basal ES, gap junctions, and desmosomes between Sertoli cells near the base of the seminiferous epithelium. the anchoring junction found between mammalian cells and the ECM, which is absent in the testis. In the testis, the basement membrane is a modified form of ECM comprising type IV collagen, laminins (e.g., laminin-α1, -α2, -β1, -β2, and -γ1 chains), heparan sulfate proteoglycans, and entactin. While there is no FAC in the testis, proteins pertinent to FACs (e.g., FAK, integrin-linked kinase) are found at the apical ES. a nonreceptor protein tyrosine kinase (PTK), that serves as signaling protein downstream of integrin-based receptors in the mammalian body. It is also the downstream signaling protein of F5-peptide in the testis. FAK works in concert with c-Src [a member of the Src family kinases (SFKs) and nonreceptor PTKs] to modulate cell adhesion, cell cycle progression, cell survival, proliferation, and differentiation. 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