Infection and inflammation of the male reproductive tract are accepted as important aetiological factors of infertility. With regard to their impact on male reproductive function, orchitis and epididymo-orchitis due to local or systemic infection as well as noninfectious aetiological factors are of particular concern. There is clinical and pathological evidence that chronic inflammatory conditions of the testes can disrupt spermatogenesis and irreversibly alter both sperm number and quality. In the majority of patients, however, diagnosis is hampered by an asymptomatic course of the disease and unspecific clinical signs. Hence, respective epidemiological data are scarce. On the other hand, systematic histopathological work-up of testicular biopsies from infertile men indicates a high prevalence of inflammatory reactions. A characteristic pattern of inflammatory lesions with focal or multifocal, predominantly peritubular lymphocyte infiltration and concomitant damage of seminiferous tubules is seen in chronic orchitis of various origins. This supports the concept that induction of testicular inflammation is associated with a T-cell-mediated autoimmune response, i.e. disruption of the immune privilege. Moreover, despite the patchy distribution of the lesions, testicular volume and score counts for spermatogenesis may be significantly reduced. In conclusion, asymptomatic inflammatory reactions in the testis should not be neglected as an underlying cause or co-factor of male infertility. However, definitive diagnosis of chronic asymptomatic orchitis still requires testicular biopsy and guidelines for the therapeutic management are not yet available.

Available data provide sufficient evidence that in men with alterations of the ejaculate, urogenital infections and inflammation have to be considered.

The concept that an elevation of testicular temperature results in impairment of spermatogenesis is widely accepted. Here, current knowledge concerning genital heat stress and its consequences in men is reviewed. Duration of sitting during work positively correlates with daytime scrotal temperatures and daytime scrotal temperature negatively correlates with semen quality. However, the assumed negative correlation between duration of sitting and semen quality could not be shown in the available studies. Fertility parameters of professional drivers with long periods of sitting in vehicles were impaired; however, for predominantly affected drivers of vans, trucks or industrial heavy machinery potential confounders have to be considered. Wearing tight fitting compared with loose-fitting underwear is associated with significantly higher scrotal temperatures. However, available observations suggesting a link between tight-fitting underwear or trousers and impaired semen quality are not convincing. Studies addressing professional exposure to high temperatures delivered conflicting results concerning fertility parameters. The postulated negative impact of sauna visits on semen quality is not sufficiently underlined by the available studies. Oligozoospermic men with a varicocele have significantly higher scrotal temperatures than normozoospermic men, and according to several studies varicocelectomy normalises scrotal temperatures. A further link has been reported between fever and deteriorated semen quality. Contraception via genital heat stress has been demonstrated using hot sitting baths or insulating suspensors. However, down-regulation of spermatogenesis is inconsistent and unsafe. On the other hand, scrotal and consecutively testicular cooling is able to improve semen quality.

No abstract

SUMMARYExisting literature suggests evidence that protamine deficiency is related to DNA damage and male fertility. In this meta-analysis, we analyzed the relationship between the ratio of protamine-1 and protamine-2 with male fertility and the association of protamine deficiency with sperm DNA damage. Quality of available cohort studies was evaluated using the Newcastle-Ottawa Scale checklist. Summary effect estimates with 95% confidence intervals (CI) were derived using a random effects model. The effect of the protamine ratio on male fertility was analyzed in nine studies demonstrating a significantly higher value of the protamine ratio in subfertile men (n = 633) when compared with controls (n = 453, SMD = 0.46, 95% CI 0.25-0.66, Z = 4.42, p < 0.00001). Both protamine mRNA (SMD = 0.45, 95% CI 0.11-0.79, Z = 2.63, p = 0.009) and protein ratio (SMD = 0.46, 95% CI 0.25-0.68, Z = 4.22, p < 0.0001) showed significantly increased values in subfertile patients. The association between protamine deficiency and DNA damage was analyzed in 12 studies (n = 845) exhibiting a combined overall correlation coefficient (COR) of 0.53 (95% CI 0.28-0.71, Z = 3.87, p < 0.001). Protamine deficiency measured by CMA3 staining was significantly associated with sperm DNA damage (COR = 0.71, 95% CI 0.48-0.85, Z = 4.87, p < 0.001), whereas the P1/P2 ratio was not (COR = 0.17, 95% CI À0.16 to 0.46, Z = 0.99, p = 0.33). It is concluded that the protamine ratio represents a suitable biomarker for the assessment of sperm quality and protamine deficiency is closely related with sperm DNA damage.

Summary.  In the past years, there has been increased interest in assessing the relationship between impaired male fertility and environmental factors. Human male fertility is a complex process and therefore a great variety of sites may be affected by exogenous noxae. Lifestyle factors as well as various environmental and occupational agents may impair male fertility. Many studies have been published reporting on reproductive dysfunctions in male animals and humans. Especially environmental pollutants with endocrine activity are discussed as a possible cause of this detrimental development. Evidence from animal experiments show that substances with oestrogenic and antiandrogenic properties may cause hypospadia, cryptorchidism, reduction of sperm density and an increase of testicular tumours. Many adverse effects on animal male fertility have been documented for phthalates and some chlorinated hydrocarbons such as polychlorinated biphenyls and polychlorinated dibenzo‐p‐dioxins. For other chemicals such as bisphenol A and nonylphenols animal data are conflicting. Environmental pollutants may mediate their effects by receptor binding, modulation of hormone‐regulated mechanisms or direct toxic effects. Data on environmental chemicals and human male fertility are scarce, and risk assessment is mostly based on the results of animal studies. However, there are indications that exposure to endocrine active chemicals during early development may alter hormone responsiveness in adulthood. Furthermore, some of the chemicals are found in fluids that are associated with human reproduction, such as follicular fluid, seminal fluid and cervical mucus. Recent studies suggest a correlation between pesticide exposure and standard semen parameters as well as in vitro fertilization rates.

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.

Signs of infections and inflammation in the ejaculate of infertile men are common, and the relevance is often doubtful in spite of microbiological, spermatological and immunological facilities.