Grant: Operating Grant - PA: Reproductive and Child Heath (start-up grants)

Infertility is an important human health problem. About 15% of couples worldwide are affected by infertility and half of these cases can be traced to men. Although the infertile population is growing over the years, there is not yet treatment for 40-50% of couples, because the etiology is not known. Several factors are associated with infertility, such as exposure to environmental pollutants, chemicals, drugs, smoking, toxins, radiation, and even diseases such as cancer and diabetes. Of particular interest are young cancer patients who suffer from impaired fertility because chemotherapy causes damage of germ cells even several years after the treatment. Male infertility is often associated with elevated levels of reactive oxygen species (ROS) produced in semen. ROS are normally formed during cellular metabolism and cells are equipped with an enzymatic and non-enzymatic antioxidant system, keeping the ROS concentration low. When ROS are produced in high amounts, the antioxidant system is overwhelmed and the resulting oxidative stress becomes injurious, affecting the normal cell function. Increased amounts of ROS are produced by diseases such as diabetes and also because of anticancer chemotherapy. Most types of cells under specific conditions also generate low and controlled amounts of ROS that are involved in the regulation of physiological processes. Similarly, low levels of ROS are required for spermatozoa to achieve fertilizing competence. Peroxiredoxins (PRDX) are newly discovered antioxidant enzymes with the capacity to regulate ROS signaling and are potential candidates as modulator of ROS effects during spermatogenesis and epididymal maturation(processes that generate healthy spermatozoa)and in sperm function. Our aim is to decipher the role PRDX in the mechanisms linked to the acquisition of fertility and those involved in the pathology of infertility. These studies will bring more knowledge to setup new diagnostic tools and treatment for men infertility.