Mazdak Razi1, Marziyeh Tavalaee2, Farshid Sarrafzadeh-Rezaei3, Aron Moazamian4, Parviz Gharagozloo4, Joël R Drevet5, Mohammad-Hossein Nasr-Eshafani2. 1. Department of Basic Sciences, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran. 2. Department of Animal Biotechnology, Reproductive Biomedicine Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran. 3. Department of Surgery and Diagnostic Imaging, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran. 4. CellOxess LLC, Ewing, New Jersey, USA. 5. Faculty of Medicine, GReD Institute, INSERM U1103, CNRS UMR6293, Université Clermont Auvergne, Clermont-Ferrand, France.
Abstract
BACKGROUND: Varicocoele (VCL), one of the main causes of male subfertility, negatively affects testicular function. Due to limited access to human testicular tissue, animal model studies have been used to evaluate molecular and, recently, epigenetic changes attributed to pathophysiology induced by VCL. OBJECTIVES: This review aims to provide an update on the latest findings regarding the link between VCL-induced biochemical stress and molecular changes in germ cells and spermatozoa. Endocrine and antioxidant status, testicular chaperone-specific hemostasis failure, altered testicular ion balance, metabolic disorders, and altered carbon cycling during spermatogenesis are among the many features that will be presented. DISCUSSION: Literature review coupled with our own findings suggests that ionic imbalance, hypoxia, hyperthermia, and altered blood flow could lead to severe chronic oxidative and nitrosative stress in patients with VCL leading to defective spermatogenesis and impairment of the integrity of all sperm cell components and compartments down to the epigenetic information they carry. CONCLUSION: Since oxidative stress is an important feature of the reproductive pathology of VCL, therapeutic strategies such as the administration of appropriate antioxidants could be undertaken as a complementary non-invasive treatment line.
BACKGROUND: Varicocoele (VCL), one of the main causes of male subfertility, negatively affects testicular function. Due to limited access to human testicular tissue, animal model studies have been used to evaluate molecular and, recently, epigenetic changes attributed to pathophysiology induced by VCL. OBJECTIVES: This review aims to provide an update on the latest findings regarding the link between VCL-induced biochemical stress and molecular changes in germ cells and spermatozoa. Endocrine and antioxidant status, testicular chaperone-specific hemostasis failure, altered testicular ion balance, metabolic disorders, and altered carbon cycling during spermatogenesis are among the many features that will be presented. DISCUSSION: Literature review coupled with our own findings suggests that ionic imbalance, hypoxia, hyperthermia, and altered blood flow could lead to severe chronic oxidative and nitrosative stress in patients with VCL leading to defective spermatogenesis and impairment of the integrity of all sperm cell components and compartments down to the epigenetic information they carry. CONCLUSION: Since oxidative stress is an important feature of the reproductive pathology of VCL, therapeutic strategies such as the administration of appropriate antioxidants could be undertaken as a complementary non-invasive treatment line.
Authors: Pietro Antonuccio; Antonio Girolamo Micali; Carmelo Romeo; Jose Freni; Giovanna Vermiglio; Domenico Puzzolo; Francesco Squadrito; Natasha Irrera; Herbert R Marini; Rosa Alba Rana; Giovanni Pallio; Letteria Minutoli Journal: Int J Mol Sci Date: 2021-01-28 Impact factor: 6.208
Authors: Pietro Antonuccio; Herbert Ryan Marini; Antonio Micali; Carmelo Romeo; Roberta Granese; Annalisa Retto; Antonia Martino; Salvatore Benvenga; Salvatore Cuzzocrea; Daniela Impellizzeri; Rosanna Di Paola; Roberta Fusco; Raimondo Maximilian Cervellione; Letteria Minutoli Journal: Nutrients Date: 2021-02-25 Impact factor: 5.717