Unraveling the Molecular Impact of Sperm DNA Damage on Human Reproduction

Semen analysis is the cornerstone in the investigation of fertility status of male partner. However, more advanced tests have emerged including the analysis of sperm chromatin integrity and DNA damage as markers of semen quality. This is of particular interest, as preserving the genetic information is essential to achieve a successful reproductive event. Moreover, the presence of unrepaired DNA lesions can affect cellular functions, resulting in the onset of pathological conditions associated with male infertility, and the transmission of diseases to the offspring. Hence, in this chapter, we aim to review the main factors leading to sperm DNA damage, along with the different types of damage which can occur. Furthermore, molecular mechanisms involved in DNA repair during spermatogenesis or after fertilization of the oocyte are described, and the laboratory techniques currently used in diagnostics and research, for the analysis of sperm DNA damage are also presented. Finally, the impact of sperm DNA damage on reproductive outcomes such as fertilization and pregnancy rates will be discussed with a focus on animal and human studies, along with the identification of new markers of sperm chromatin integrity.