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Male subfertility has been associated with bacterial infections and chronic inflammation. In this context, several studies investigated cytokine levels in seminal plasma, whereas interleukin-6 (IL-6) appears to be crucial. However, little is known about its receptor, the IL-6R expression on human spermatozoa. Thus, the aim of the present study was to screen spermatozoa for IL-6R expression and to identify its localisation. Semen samples of 137 patients (median age 37.69, SD ± 7.82) with subfertility were analysed. Sperm analysis including determination of IL-6 was performed following the World Health Organization criteria. Also, flow cytometry was performed for sperm IL-6R expression. IL-6R + cells were used for immunofluorescence staining to identify receptor localisation. The results showed positive staining for IL-6R in the midpiece of spermatozoa. Furthermore, a significant correlation between sperm IL-6R expression, seminal plasma IL-6 and total sperm count could be demonstrated, whereas a negative correlation was observed in sperm IL-6R expression and motility. However, no statistical significance could be observed between IL-6R expression, vitality and morphology. Moreover, incubation of spermatozoa with IL-6 led to a slight but significant decrease in motility after 24 hr. These data suggest that IL-6R expression may play a role in impaired sperm function during inflammation., (© 2020 The Authors. Andrologia published by Blackwell Verlag GmbH.)

Background: Reactive oxygen species (ROS) are an array of molecules including oxygen-centered radicals, which are endowed with one or more unpaired electrons and non-radical oxygen derivatives such as hydrogen peroxide, which behave, to a large extent, like a double-edged sword in human sperm biology. This study aimed to overview the current knowledge of ROS in sperm physiology and pathology, as well as related therapies in spermatozoal dysfunction., Methods: We performed this study by searching for keywords from PUBMED, including reactive oxygen species, oxidative stress, sperm function, and antioxidant therapy., Results and Conclusions: Low levels of ROS exert critical function in normal sperm physiology, such as fertilizing ability (acrosome reaction, hyperactivation, capacitation, and chemotaxis) and sperm motility; while increased ROS generation and/or decreased antioxidant capacity leads to the imbalance between oxidation and reduction in living systems, which is called sperm oxidative stress. This condition was widely considered to be a significant contributory factor to sperm DNA damage/apoptosis, lipid peroxidation, and reduced motility, which in turn, increased risk of male factor infertility/subfertility and birth defects. Under the current status quo, numerous subsequent studies have concentrated on antioxidant therapy. Although utility of such a therapeutic strategy significantly improved sperm function and motility in a myriad of experimental and clinical reports, the overall effectiveness still remains controversial mainly due to non-standardized assay to measure the level of ROS and sperm DNA damage, various antioxidant supplementation strategies, and inadequate fertilization and pregnancy data after clinical treatment. Therefore, standardized assessment and evaluation of ROS and total antioxidant capacity in semen should be established to keep ROS in a physiological level and prevent over-treatment of antioxidants toward reductive stress, which should be kept in mind, especially in assisted reproductive procedure. Moreover, the significance of large sample size populations, double-blind randomized, placebo-controlled clinical trials of antioxidant therapies is emphasized in this review to achieve optimal ingredients and dosage of antioxidants for patients with reactive oxygen-induced male fertility/subfertility.

The longest part of the sperm flagellum, the principal piece, contains the fibrous sheath, a cytoskeletal element unique to spermiogenesis. We performed mass spectrometry proteomics on isolated human fibrous sheaths identifying a unique ADP/ATP carrier protein, SFEC [AAC4], seven glycolytic enzymes previously unreported in the human sperm fibrous sheath, and sorbitol dehydrogenase. SFEC, pyruvate kinase and aldolase were co-localized by immunofluorescence to the principal piece. A homology model constructed for SFEC predicted unique residues at the entrance to the nucleotide binding pocket of SFEC that are absent in other human ADP/ATP carriers, suggesting opportunities for selective drug targeting. This study provides the first evidence of a role for an ADP/ATP carrier family member in glycolysis. The co-localization of SFEC and glycolytic enzymes in the fibrous sheath supports a growing literature that the principal piece of the flagellum is capable of generating and regulating ATP independently from mitochondrial oxidation in the mid-piece. A model is proposed that the fibrous sheath represents a highly ordered complex, analogous to the electron transport chain, in which adjacent enzymes in the glycolytic pathway are assembled to permit efficient flux of energy substrates and products with SFEC serving to mediate energy generating and energy consuming processes in the distal flagellum, possibly as a nucleotide shuttle between flagellar glycolysis, protein phosphorylation and mechanisms of motility.

Chronic inflammation of genital tract is thought to play a major role in male fertility disorder. Natural killer ( NK) T cells are a heterogeneous group of T cells that share properties of both T cells and NK cells which display immunoregulatory properties. However, little is known regarding the presence and function of NK T cells in ejaculates from patients with chronic inflammation of genital tract. Invariant NK T ( iNK T) cells were detected by invariant (Vα24-JαQ) TCR chain in ejaculates from patients suffering from chronic inflammation of genital tract ( CIGT) using flow cytometry and immunofluorescence of double staining (n =40). Inflammatory cytokines interleukin ( IL)-6, IL-17, and IFN-γ were detected in cell-free seminal plasma using an enzyme-linked immunosorbent assay ( ELISA). The correlation between the percentage of iNK T cells and spermatozoa count, motility, vitality, seminal IL-6, IL-17, and IFN-γ was investigated. Significant percentages of iNK T cells above 10% were detected in 50% ( CIGT- NKT+ group). A negative correlation was detected between the percentage of iNK T cells and spermatozoa count ( r=−.5957, P=.0056), motility ( r=−.6163, P=.0038), and vitality ( r=−.8032, P=.0019) in CIGT- NKT+ group (n=20). Interestingly, a significant correlation of iNK T cells to seminal IL-6 ( r=.7083, P=.0005), IFN-γ ( r=.9578, P<.0001) was detected whereas lack of correlation between iNK T cells and IL-17 ( r=−.1557, P=.5122) in CIGT- NKT+ group. The proliferative response of iNK T cells could accompany an inflammatory response to spermatozoa and consequently influence sperm quality through secretion of IFN-γ but not IL-17 under chronic inflammatory condition. [ABSTRACT FROM AUTHOR]