Risk assessment of chemicals potentially affecting male fertility

Male reproductive toxicity involves a broad range of targets and mechanisms such as direct effects on the seminiferous epithelium and/or on Leydig and Sertoli cells supporting spermatogenesis, epididymal sperm maturation as well as endocrine disruption. Direct effects on spermatogenesis may be adequately revealed through both reproduction and repeated-dose toxicity studies; however, more research is needed on early markers of effect and on long-term sequelae of short-term exposures. Endocrine-related mechanisms are particularly relevant to subtle, but persistent effects on reproductive development due to altered early programming; the two-generation study is the test of choice, whereas targeted studies on the prepubertal phase are also desirable. Studies using in vitro methods as well as toxicogenomics are increasing; although gaps exist and much validation work is needed, in perspective, such approaches may be important in order to select compound, understand mechanisms, as well identify biomarkers of potential use also in human studies.