Genital tract infection and reduced sperm motility are considered two pivotal etiological factors for male infertility associated with leukocytospermia and asthenozoospermia, respectively. We demonstrate that the amount of human β-defensin 1 (DEFB1) in sperm from infertile men exhibiting either leukocytospermia or asthenozoospermia, both of which are associated with reduced motility and reduced bactericidal activity in sperm, is much lower compared to that in normal fertile sperm. Interference with DEFB1 function also decreases both motility and bactericidal activity in normal sperm, whereas treatment with recombinant DEFB1 markedly restores DEFB1 expression, bactericidal activity, sperm quality, and egg-penetrating ability in sperm from both asthenozoospermia and leukocytospermia patients. DEFB1 interacts with chemokine receptor type 6 (CCR6) in sperm and triggers Ca(2+) mobilization, which is important for sperm motility. Interference with CCR6 function also reduces motility and bactericidal activity of normal sperm. The present finding explains a common defect in male infertility associated with both asthenozoospermia and leukocytospermia, indicating a dual role of DEFB1 in defending male fertility. These results also suggest that the expression of DEFB1 and CCR6 may have diagnostic potential and that treatment of defective sperm with recombinant DEFB1 protein may be a feasible therapeutic approach for male infertility associated with poor sperm motility and genital tract infection.
In view of these data, a picture emerges that IL-17-producing cells in CP could be in part directed by CD68(+) Mo-like cells, which produce IL-23p19 upon TLR4 activation by Pg.
Infection and inflammation of the male reproductive tract are thought to be a primary aetiological factor of male infertility. Furthermore, several studies suggest that T lymphocytes are critically involved as regulator in the pathogenesis of male infertility under these conditions and are thought to induce autoimmune orchitis. In this context of autoimmunity the recently described T helper (Th) 17 subset has been suggested to play an essential role so that the aim of this study was to investigate the expression and characteristics of Th17 cells as well as the presence of Th17 inducing antigen presenting cells (APCs) in azoospermic testis with chronic inflammation (ATCI) compared with normal spermatogenesis. By stereological analysis, we detected base line expression of Th17 cells in Con. However, increased expression intensity and number of Th17 cells and their cytokines [interleukin (IL)-17A, IL-21, IL-22] and a decreased level of Foxp3(+) and interferon-γ(+) cells could be demonstrated in ATCI. Moreover, along with these data, increased numbers of Th17-inducing IL-23 producing CD11c(+) and CD68(+) APCs could be detected in ATCI. From these data, a picture emerges that Th17 cells orchestrated by IL-23 producing APCs are critically involved in chronic inflammation in ATCI.
Highlights d Four methods, PCA, MDS, t-SNE, and UMAP, are evaluated on 71 bulk transcriptomic datasets d UMAP is overall superior to PCA and MDS and shows some advantages over t-SNE d UMAP can efficiently and effectively reveal clusters in twodimensional space d Clusters revealed by UMAP are associated with biological features and clinical traits
Increased numbers of mast cells (MCs) were described in the testes of males exhibiting infertility many years ago. Since beneficial effects of treatment with MC blockers on impaired male fertility were reported, more attention has been drawn on the role of MCs in the male reproductive tract. The main interest is focused on testicular MCs, however MCs also occur in the epididymis and seminal fluid, which may be relevant for fertility as well. The increase in testicular MCs in close contact to the seminiferous tubules indicates a relationship between MC proliferation and a dysfunction of the blood-testis barrier. Activated MCs not only coincide with fibrotic events, but also with elevated numbers of several types of immune cells in the testes of infertile men and may, therefore, be involved in the pathogenesis of testicular inflammatory processes as well. Outside the testis, MCs have really been assigned a key role in chronic protatitis/chronic pelvic pain syndrome. The occurrence of MCs in the seminal plasma of fertile/infertile men and negative effects on sperm functions has not been clarified so far and require further investigation. Optimistic reports on the beneficial effects of the treatment with MC blockers on disturbed male fertility also warrant further confirmation.
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