PRE-CLINICAL EVIDENCES THAT ANTIOXIDANT SUPPLEMENTATION CORRECTS SPERM DNA OXIDATIVE DAMAGE AND IMPROVES REPRODUCTIVE SUCCESS

Abstract

Gamete nuclear integrity is the most critical parameter to ensure complete and harmonious embryonic development. It is also a major contributor to the health and wellbeing of the progeny. The most frequent sperm DNA alteration in natural as well as in assisted reproduction involves an oxidative attack, leading to the formation of oxidized base adducts such as 8-hydroxy-2'-deoxyguanosine. Oxidative alterations of the paternal genome that are not efficiently repaired by the oocyte or not compensated by the maternal genome emphasize the risk of trans-generational effects that may be increased when fertilization involves such spermatozoa showing high oxidative DNA damage. It may partly explain the low efficacy of assisted reproductive technologies. We will show here that oral antioxidant supplementation using a well-designed formulation significantly reduces sperm DNA damage (SDD) in GPX-5 knockout mice and restores pregnancy rates almost back to normal levels in mice subjected to Scrotal Heat Stress (SHS). These results, if confirmed in humans, might impact clinical fertility practice since current clinical studies confirm moderate to severe SDD in about 60% of all men visiting IVF centers and in about 80% of men diagnosed with idiopathic male infertility, figures which are gravely concerning. Antioxidant supplementation could be an adjuvant therapy prior to undertaking ART procedures to improve fertilization rates, maintain a healthy pregnancy, and reduce de novo sporadic mutations being passed onto children.