title: Antioxidative effects of cerium dioxide nanoparticles ameliorate age-related male infertility: optimistic results in rats and the review of clinical clues for integrative concept of men health and fertility.
abstract: BACKGROUND
  Male infertility has largely idiopathic, multifactorial origin. Oxidative stress is a major factor that affects spermatogenesis, in particular in aging. Cerium dioxide nanoparticles (CNPs) due to their antioxidative properties are promising to impact on the development of male infertility. The aims of this study were to investigate the effects of CNPs on fertility parameters in 24-month male rats and to overview relevant literature in the field of personalized treatments, predictive diagnosis, and preventive measures for male health and fertility.
  
  
  METHODS
  We included 30 24-month-old male rats. After a week of adaptation to the standard diet, the rats were randomly divided into three groups with ten rats in each. Group 1 (controls) received only a standard diet. The rats of group 2 and 3 in adjunct to the standard diet during 10 days received intragastrically 10 % sodium citrate and citrate-coated CNPs in dose 1 mg/kg, respectively. We assessed sex hormones, epididymal sperm parameters and spermatogenesis, ultrasound, and morphological data of rat reproductive organs.
  
  
  RESULTS
  After a 10-day administration of CNPs, we revealed significant decrease of lipid peroxidation product levels in serum and increase of catalase and SOD activity, associated with increase of sperm count (p < 0.001) and improvement in quantitative sperm parameters (motility, viability, and percentage of spermatozoa). We found no significant changes between sperm quantitative parameters in citrate-treated rats and controls and observed age-related decrease of activated Leydig cell number and focal atrophy of the seminiferous tubules. In CNP group, we observed regeneration of seminiferous tubules, increase number and activation of Leydig cells, and 2.5-fold significant increase of serum testosterone. Ultrasound data showed the slight increase of linear measurement and volume of rat testes in CNP group. Review highlights the benefits for predictive diagnosis, preventive measures, and personalized approaches to manage male infertility in the general concept of male health also related to aging.
  
  
  CONCLUSIONS
  Citrate-coated 2-5-nm CNPs lead to increase in sex hormones levels, sperm count, and quality, as well as the activation of spermatogenesis in 24-month-old male rats. Nanoceria demonstrated the perspectives to be an effective infertility treatment via reduction of oxidative stress in male reproductive organs, in particular in aging.
authors.affiliation: Bogomolets National Medical University, T. Shevchenko boulevard, 13, Kyiv, 01601 Ukraine.
authors.forename: Nazarii M
authors.initials: NM
authors.lastname: Kobyliak
authors.affiliation: Taras Shevchenko National University of Kyiv, Volodymyrska Str., 64/13, Kyiv, 01601 Ukraine.
authors.forename: Tetyana M
authors.initials: TM
authors.lastname: Falalyeyeva
authors.affiliation: State Scientific Enterprise "Scientific Practical Center for Prophylactic and Clinical Medicine" State Management of Affairs Department, Kyiv, Ukraine, Verhnya str., 5, Kyiv, 01014 Ukraine.
authors.forename: Olena G
authors.initials: OG
authors.lastname: Kuryk
authors.affiliation: Taras Shevchenko National University of Kyiv, Volodymyrska Str., 64/13, Kyiv, 01601 Ukraine.
authors.forename: Tetyana V
authors.initials: TV
authors.lastname: Beregova
authors.affiliation: Bogomolets National Medical University, T. Shevchenko boulevard, 13, Kyiv, 01601 Ukraine.
authors.forename: Petro M
authors.initials: PM
authors.lastname: Bodnar
authors.affiliation: Zabolotny Institute of Microbiology and Virology, National Academy of Sciences of Ukraine, Zabolotny Str., 154, Kyiv, 03680 Ukraine.
authors.forename: Nadiya M
authors.initials: NM
authors.lastname: Zholobak
authors.affiliation: Zabolotny Institute of Microbiology and Virology, National Academy of Sciences of Ukraine, Zabolotny Str., 154, Kyiv, 03680 Ukraine.
authors.forename: Oleksandr B
authors.initials: OB
authors.lastname: Shcherbakov
authors.affiliation: Zabolotny Institute of Microbiology and Virology, National Academy of Sciences of Ukraine, Zabolotny Str., 154, Kyiv, 03680 Ukraine ; Clinical Hospital 'Pheophania' of State Management of Affairs Department, Zabolotny Str., 21, Kyiv, 03680 Ukraine.
authors.forename: Rostyslav V
authors.initials: RV
authors.lastname: Bubnov
authors.affiliation: Zabolotny Institute of Microbiology and Virology, National Academy of Sciences of Ukraine, Zabolotny Str., 154, Kyiv, 03680 Ukraine ; LCL "DIAPROF", Svitlycky Str., 35, Kyiv, 04123 Ukraine.
authors.forename: Mykola Ya
authors.initials: MY
authors.lastname: Spivak
keywords: Age-related male infertility; Infertility biomarkers; Men health; Nanocrystalline cerium dioxide; Oxidative–antioxidative balance; Predictive, preventive, and personalized medicine; Seminal plasma; Translation; Ultrasound