Cytokines and Spermatogenesis

Testes are considered to be an immunoprivileged organ due to their tolerance of autoantigens secreted during sexual maturity by reproductive cells. This phenomenon supports spermatogenesis [6 ] . The mechanisms which protect testes against autoimmune diseases are immunological/anatomical blood-testis barrier (BTB) which protects against the antigenic leakage out of germ cells to immunological, intraparenchymal cells and against the transition of antibodies from endothelium to the lumen of seminiferous tubules; secretion of immunosuppressive factors by macrophages, the Sertoli, Leydig, and peritubular cells; and a limited presence of activated T lymphocytes (particularly that of CD8+) and the presence of regulatory T lymphocytes. Maintenance of the balance between inflammation and "immunoprivileged" gonad belongs, among other, to the function of cytokines which perform both the roles as proinflammatory mediators and immunosuppressive ones [7].

BTB consists of vascular endothelium, basal lamina of seminiferous tubules, and specialized tight junctions (TJs) between Sertoli cells. BTB creates microenvironment in which spermatogenesis takes place: meiosis, spermiogenesis, and sperm-iation. BTB ensures polarization of Sertoli cells and regulates intercellular transfer of water, ions, feeding substances, and biomolecules to germ cells from circulation. BTB regulation is ensured by activated TGFb and tumor necrosis factor (TNF)-a, mitogen-activated protein kinase (MAPK), and c-Jun N-terminal kinase signaling pathways [8-11].

Ectoplasmic specialization (ES) is a junction located in two testicular areas: among postmeiotic spermatids and Sertoli cells of seminiferous tubules—apical ES is involved in migration of preleptotenic spermatocytes in stage VIII of seminiferous epithelium through BTB itself and between BTB and Sertoli cells—basal ES [12] functions with tightjunctions, desmosomes, and gapjunctions that are components of BTB [12-14].

Cytokines do not only play a role at directing germ cells to apoptosis, but TNF-a, TGF-P2, and TGF-P3 together with testosterone regulate spermatogenesis [9, 15].

Receptors for cytokines, i.e., TGF-b and TNF, are located on Sertoli cells which regulate migration of germ cells through the barrier to adluminal compartment [15]. One of the physiological roles of cytokines is to restructure BTBjunctions and apical ES during migration of preleptotenic spermatocytes [16]. Restructuring of junctions in seminiferous epithelium depends on the changes in protein phos-phorylation [17],

Cytokines may influence apical ES as well as the whole BTB through altering protein levels present in biological membranes as N-cadherin in the case of apical ES and occludin in BTB. In consequence of their action is an increase in protein endocytosis and intracellular endosome-mediated degradation [18].

Ovulation Immune

Fig. 9.1 The apical ES-blood-testis barrier (BTB)-hemidesmosome axis. Matrix proteinase-2 uncouples integrin-laminin complex and releases biologically active laminin protein fragments, which induce disruption of the "old" BTB proteins and also hemidesmosomes. The disrupted junction proteins undergo endocytosis. The endocytosed proteins are subject of endosome-mediated degradation with transforming growth factor (TGF) participation. These proteins can also be tran-scytosed in order to assembly new BTB in the presence of testosterone and tumor necrosis factor (TNF)

Fig. 9.1 The apical ES-blood-testis barrier (BTB)-hemidesmosome axis. Matrix proteinase-2 uncouples integrin-laminin complex and releases biologically active laminin protein fragments, which induce disruption of the "old" BTB proteins and also hemidesmosomes. The disrupted junction proteins undergo endocytosis. The endocytosed proteins are subject of endosome-mediated degradation with transforming growth factor (TGF) participation. These proteins can also be tran-scytosed in order to assembly new BTB in the presence of testosterone and tumor necrosis factor (TNF)

In opposition to cytokine action testosterone increases BTB integrity and enhances protein production as elements of Sertoli cells tight junctions essential for functioning and barrier stability [19, 20] (Fig. 9.1).

Testosterone and cytokines demonstrate antagonistic action on integrity of BTB within seminiferous proteins of BTB system and stabilize BTB tight junctions (Fig. 9.1) . However, only testosterone directs proteins after endocytosis to renew their utilization on the membrane surface of Sertoli cells, induces "de novo" synthesis of integral proteins of BTB membrane, and promotes transcytosis through the protein relocation from the "old" to the "new" BTB side. Cytokines after endocy-tosis induce degradation of "old" TJ fibrils. TNF-a function is different from the remaining ones and acts on androgenic receptor, and promotes testosterone activity. In this way, transport of preleptotenic spermatocytes through BTB barrier takes place [9, 15, 21],

Coordination of restructuring of apical ES and BTB during spermatogenesis takes place at participation of apical ES-BTB-hemidesmosome functional axis. Reaction cascade begins before spermiation through action of metalloproteinase-2 which cleaves complex integrin-laminin releasing fragments of active laminin that may cause cytokine synthesis, influence endocytosis kinetics, recycling, transcyto-sis, or protein degeneration. It is suggested that metalloproteinase-2 influences the induction of BTB restructuring by TNF mediation. TNF also acts on production of metalloproteinase-9 in Sertoli cells which alters functioning of tight BTB junctions through cleavage of collagen [22-24].

Pregnancy Guide

Pregnancy Guide

A Beginner's Guide to Healthy Pregnancy. If you suspect, or know, that you are pregnant, we ho pe you have already visited your doctor. Presuming that you have confirmed your suspicions and that this is your first child, or that you wish to take better care of yourself d uring pregnancy than you did during your other pregnancies; you have come to the right place.

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