P Mohammadi - Department of Reproductive Biotechnology, Reproductive Biomedicine Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran- Anatomical Sciences Research Center, Kashan University of Medical Sciences, Kashan, Iran
H Hassani Bafrani - Anatomical Sciences Research Center, Kashan University of Medical Sciences, Kashan, Iran- Gametogenesis Research Center, Kashan University of Medical Sciences, Kashan, Iran
M Tavalaee - Department of Reproductive Biotechnology, Reproductive Biomedicine Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran
MH Nasr-Esfahani - Department of Reproductive Biotechnology, Reproductive Biomedicine Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran

Background: Varicocele is one of the most prevalent causes of infertility. It causes induction of oxidative stress, increases lipid peroxidation and DNA fragmentation in the testis and disrupts spermatogenesis cycle. Balanced diet is the natural source of micronutrients, such as folate and vitamins, vital for proper functioning of the body.Objective: To demonstrate that micronutrients in support of the one-carbon cycle and glutathione synthesis are effective in improving sperm damage following surgical varicocele in rats and that this effect is achieved without suffering a rebound reductive stress as seen with oral antioxidants. Materials and Methods: Surgical varicocele was induced in adult male Wistar rats and resulted in significant damage to testis and sperm cells measured 2 and 4 months post-surgery. Two months after surgery, rats received a 2-month oral supplementation in support of the one-carbon cycle containing B vitamins (B2, B3, B6, folic acid and B12), N-acetyl-cysteine, zinc, small amounts of Vitamin E and a natural source of betalains and quercetine (Condensyl).Results: One-carbon cycle supplementation, compared to untreated controls, significantly improved the morphometric characteristics of testis (p<0.05), sperm concentration, motility and abnormal morphology (p<0.001), sperm chromatin condensation (aniline blue staining, p<0.05), sperm DNA damage (acridine orange staining, p<0.05) and sperm lipid peroxidation (BODIPY C11, p<0.001). The improvement of both nuclear condensation and DNA damage and the lack of excessive inhibition of lipid peroxidation confirmed that no reductive stress had occurred.Conclusion: Micronutrients in support of the one-carbon cycle are effective in the treatment of the rat experimental varicocele, likely by activating the natural antioxidant defenses and epigenetics. These results support the idea that essential micronutrients Accepted Article This article is protected by copyright. All rights reserved. Including B vitamins may have a positive influence also in clinical varicocele, which should be tested in prospective clinical trials.

Condensyl, DNA damage, Lipid peroxidation, Nuclear condensation, Varicocele