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International Journal of Fertility and Sterility، جلد ۸، شماره ۲.۵، صفحات ۱۸-۱۸
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عنوان انگلیسی O-2: A Novel Antioxidant Formulation to Treat Male Infertility Emanating from Sperm Oxidative DNA Damage: Promising Preclinical Evidence from Mouse Models
چکیده انگلیسی مقاله Background: Sperm DNA damage (SDD) is a significant male infertility factor, yet it is not routinely diagnosed or treated in couples undertaking fertility treatment by ART. Men with this condition are likely to experience sub-fertility or infertility, expose their female partners to greater risk of miscarriage and pass on de novo sporadic DNA mutations potentially compromising the health of their future generations. The present situation is gravely concerning as 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. To alleviate SDD in infertile men and effectively address this area of unmet clinical need, CellOxess scientists, after almost a decade of rigorous research, designed and developed a unique proprietary antioxidant formulation “FertilixTM”. To get an early assessment of FertilixTM efficacy in rodents, our academic collaborators in France and Spain used two independent mouse models of sperm oxidative stress to study the effect of FertilixTM in 1. the prevention of damage to sperm DNA and 2. improving fertilization and pregnancy rates. Materials and Methods: Two well-established mouse models of sperm oxidative stress from 2 independent laboratories were utilized to evaluate the efficacy of Fertilix. In both models, 12 male mice were provided with Fertilix in their drinking water for 2 weeks (Scrotal Heat Shock, SHS) or 4 weeks (Glutathione Peroxidase 5 knock out, GPX-5 KO) and compared with control groups for SDD and pregnancy rates. Results: The 8-Hydroxy-deoxy Guanosine (8-OHdG) is a biomarker of DNA oxidation. The average background levels of 8-OHdG in WT mice is around 30%. This level doubles up to about 60% in transgenic mice deficient in the antioxidant enzyme GPX-5. Our results indicate that a 2 weeks pretreatment of GPX-5 KO mice with Fertilix provides a complete protection of sperm DNA against oxidation. In mouse models of Scrotal Heat Shock (SHS), only 35% (19/54) female mice got pregnant resulting in 169 fetuses. This is contrast to the Fertilix pretreated group where 74% (42/57) female mice got pregnant resulting in 427 fetuses. The role of chance in obtaining supporting results for the efficacy of Fertilix in both models is minimal. Conclusion: Fertilix antioxidant formulation is highly efficacious in mouse models of sperm oxidative stress. Fertilix prevents SDD in GPX-5 deficient mice and restores pregnancy rates almost back to normal levels in mice subjected to SHS. These results, if confirmed in humans, will impact the normal practice at ART centers. Antioxidants will be an adjuvant therapy to a couple’s fertility treatment prior to undertaking IUI or IVF procedures.
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نشانی اینترنتی http://ijfs.ir/journal/article/abstract/3832
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