Chronic Prostatitis/Chronic Pelvic Pain Syndrome Leads to Impaired Semen Parameters, Increased Sperm DNA Fragmentation and Unfavorable Changes of Sperm Protamine mRNA Ratio.

BACKGROUND: Chronic Prostatitis/Chronic Pelvic Pain Syndrome (CP/CPPS) is a frequent disease affecting men of every age and accounting for a great number of consultations at urology departments. Previous studies suggested a negative impact of CP/CPPS on fertility. As increasing attention has been attributed to additional aspects, such as sperm DNA integrity and sperm protein alterations, besides the WHO standard semen analysis when assessing male fertility, in this prospective study, we aimed to further characterize the fertility status in CP/CPPS patients with a focus on these parameters. METHODS: Sperm DNA fragmentation measured by sperm chromatin structure assay (SCSA) and protamine 1 to protamine 2 mRNA ratio assessed by RT-qPCR were analyzed along with conventional ejaculate parameters and inflammatory markers in 41 CP/CPPS patients and 22 healthy volunteers. RESULTS: We found significant differences between the groups concerning multiple conventional ejaculate parameters. A significant increase in sperm DNA fragmentation was shown in CP/CPPS patients with association to other sperm parameters. The majority of CP/CPPS patients exhibited protamine mRNA ratios out of the range of regular fertility. CONCLUSIONS: This is a pioneering study with a strong practical orientation revealing that CP/CPPS leads to increased sperm DNA damage and changes in sperm protamine levels, emphasizing an unfavorable impact of CP/CPPS on fertility.

Elevated CCL2 causes Leydig cell malfunction in metabolic syndrome.

Metabolic syndrome (MetS), which is associated with chronic inflammation, predisposes males to hypogonadism and subfertility. The underlying mechanism of these pathologies remains poorly understood. Homozygous leptin-resistant obese db/db mice are characterized by small testes, low testicular testosterone, and a reduced number of Leydig cells. Here we report that IL-1ß, CCL2 (also known as MCP-1), and corticosterone concentrations were increased in the testes of db/db mice relative to those in WT controls. Cultured murine and human Leydig cells responded to cytokine stress with increased CCL2 release and apoptotic signals. Chemical inhibition of CCL2 rescued Leydig cell function in vitro and in db/db mice. Consistently, we found that Ccl2-deficient mice fed with a high-energy diet were protected from testicular dysfunction compared with similarly fed WT mice. Finally, a cohort of infertile men with a history of MetS showed that reduction of CCL2 plasma levels could be achieved by weight loss and was clearly associated with recovery from hypogonadism. Taken together, we conclude that CCL2-mediated chronic inflammation is, to a large extent, responsible for the subfertility in MetS by causing damage to Leydig cells.

Assessment of Oligo-Chitosan Biocompatibility toward Human Spermatozoa.

The many interesting properties of chitosan polysaccharides have prompted their extensive use as biomaterial building blocks, for instance as antimicrobial coatings, tissue engineering scaffolds, and drug delivery vehicles. The translation of these chitosan-based systems to the clinic still requires a deeper understanding of their safety profiles. For instance, the widespread claim that chitosans are spermicidal is supported by little to no data. Herein, we thoroughly investigate whether chitosan oligomer (CO) molecules can impact the functional and structural features of human spermatozoa. By using a large number of primary sperm cell samples and by isolating the effect of chitosan from the effect of sperm dissolution buffer, we provide the first realistic and complete picture of the effect of chitosans on sperms. We found that CO binds to cell surfaces or/and is internalized by cells and affected the average path velocity of the spermatozoa, in a dose-dependent manner. However, CO did not affect the progressive motility, motility, or sperm morphology, nor did it cause loss of plasma membrane integrity, reactive oxygen species production, or DNA damage. A decrease in spermatozoa adenosine triphosphate levels, which was especially significant at higher CO concentrations, points to possible interference of CO with mitochondrial functions or the glycolysis processes. With this first complete and in-depth look at the spermicidal activities of chitosans, we complement the complex picture of the safety profile of chitosans and inform on further use of chitosans in biomedical applications.