Skip to main content
Log in

Hyperbaric Oxygen Therapy Ameliorates Sperm Parameters in Apolipoprotein E Knockout Mice Testes by Attenuating Oxidative Stress and Inflammation

  • Male Reproduction: Original Article
  • Published:
Reproductive Sciences Aims and scope Submit manuscript

Abstract

Apolipoprotein E (ApoE) is a member of apolipoprotein (apo) family and plays critical role in lipid metabolism. In this study, the relationship between abnormal lipid metabolism caused by ApoE-deficient and male reproduction was investigated. The effect of hyperbaric oxygen (HBO) therapy on 7-month-old ApoE-knockout male mice was assessed subsequently. Mice were randomly divided into 3 groups: control group (WT), ApoE (− / −) group (AP-CON), and ApoE (− / −) plus HBO group (AP-HBO), which received HBO treatment. We found that ApoE knockout caused a decrease in male reproductive capacity due to the reduced total sperm motility, progressive motility (PR), and lower blastocyst formation rate. HBO treatment could accelerate serum lipoprotein metabolism including LDL, T-CHO, and TG and semen quality. As a result, fertilization and blastocyst formation of AP-HBO group were higher than that of AP-CON, proving positive therapeutic effect. Mechanism exploration found that HBO treatment ameliorated the testicular microenvironment by attenuating inflammatory factor production and oxidative stress, eventually improved the sperm motility. Collectively, our study provided more evidences of HBO treatment for improving the semen quality of patients with abnormal lipid metabolism caused by ApoE-deficient.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

Data availability

Not applicable.

Code Availability

Not applicable.

References

  1. Craig JR, Jenkins TG, Carrell DT, Hotaling JM. Obesity, male infertility, and the sperm epigenome. Fertil Steril. 2017;107:848–59.

    Article  PubMed  Google Scholar 

  2. Meldrum DR. Introduction: obesity and reproduction. Fertil Steril. 2017;107:831–2.

    Article  PubMed  Google Scholar 

  3. Ma P, Zhang Z, Zhou X, Luo J, Lu H, Wang Y. Characterizing semen abnormality male infertility using non-targeted blood plasma metabolomics. PLoS ONE. 2019;14:e0219179.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Marais AD. Apolipoprotein E in lipoprotein metabolism, health and cardiovascular disease. Pathology. 2019;51:165–76.

    Article  CAS  PubMed  Google Scholar 

  5. Wallert M, Bauer J, Kluge S, Schmolz L, Chen YC, Ziegler M, et al. The vitamin E derivative garcinoic acid from Garcinia kola nut seeds attenuates the inflammatory response. Redox Biol. 2019;24:101166.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Zhang T, Dai P, Cheng D, Zhang L, Chen Z, Meng X, et al. Obesity occurring in apolipoprotein E-knockout mice has mild effects on fertility. Reproduction. 2014;147:141–51.

    Article  CAS  PubMed  Google Scholar 

  7. Aitken RJ. Reactive oxygen species as mediators of sperm capacitation and pathological damage. Molecular Reproduction and Development. 2017;84(10):1039–1052.

  8. Khoi HX, Shimizu K, Yoneda Y, Minagawa I, Abe Y, Kuwabara Y, et al. Monitoring the reactive oxygen species in spermatozoa during liquid storage of boar semen and its correlation with sperm motility, free thiol content and seasonality. Andrologia. 2021;53:e14237.

    Article  CAS  PubMed  Google Scholar 

  9. Aitken RJ. Impact of oxidative stress on male and female germ cells: implications for fertility. Reproduction. 2020;159:R189-r201.

    Article  CAS  PubMed  Google Scholar 

  10. Aitken RJ. Reactive oxygen species as mediators of sperm capacitation and pathological damage. Mol Reprod Dev. 2017;84:1039–52.

    Article  CAS  PubMed  Google Scholar 

  11. Schneider S, Shakeri F, Trötschel C, Arévalo L, Kruse A, Buness A, et al. Protamine-2 deficiency initiates a reactive oxygen species (ROS)-mediated destruction cascade during epididymal sperm maturation in mice. Cells. 2020;9(8):1789.

  12. Amsa B, Gr A, Jpk A. Amelioration of heat stress-induced damage to testes and sperm quality - ScienceDirect. Theriogenology. 2020;158:84–96.

    Article  Google Scholar 

  13. Greish SM, Abdel Kader GS, Abdelaziz EZ, Eltamany DA, Sallam HS, Abogresha NM. Lycopene is superior to moringa in improving fertility markers in diet-induced obesity male rats. Saudi J Biol Sci. 2021;28(5):2956–2963.

  14. Rato L, Alves MG, Cavaco JE, Oliveira PF. High-energy diets: a threat for male fertility? Obes Rev. 2014;15:996–1007.

    Article  CAS  PubMed  Google Scholar 

  15. ÖzgökKangal K, Özgök Y. Assisted reproductive treatments with hyperbaric oxygen therapy in male infertility. Turk J Urol. 2021;47:98–105.

    Article  Google Scholar 

  16. Metelev AY, Bogdanov AB, Ivkinl EV, Mitrokhin AA, Vodneva MM, Veliev EI. Hyperbaric oxygen therapy in the treatment of male infertility associated with increased sperm DNA fragmentation and reactive oxygen species in semen. Urologiia. 2015;(5):74–6.

  17. Zhao Y, Qu H, Wang Y, Xiao W, Zhang Y, Shi D. Small rodent models of atherosclerosis. Biomed Pharmacother. 2020;129:110426.

    Article  CAS  PubMed  Google Scholar 

  18. Korsager Larsen M, Matchkov VV. Hypertension and physical exercise: the role of oxidative stress. Medicina (Kaunas). 2016;52:19–27.

    Article  PubMed  Google Scholar 

  19. Ikelle L, Naash MI, Al-Ubaidi MR. Oxidative stress, diabetic retinopathy, and superoxide dismutase 3. Adv Exp Med Biol. 2019;1185:335–9.

    Article  CAS  PubMed  Google Scholar 

  20. Rezaee-Tazangi F, Zeidooni L, Rafiee Z, Fakhredini F, Kalantari H, Alidadi H, et al. Taurine effects on bisphenol A-induced oxidative stress in the mouse testicular mitochondria and sperm motility. JBRA Assist Reprod. 2020;24:428–35.

    PubMed  PubMed Central  Google Scholar 

  21. Ma Q. Role of nrf2 in oxidative stress and toxicity. Annu Rev Pharmacol Toxicol. 2013;53:401–26.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Zhang X, Yu Y, Lei H, Cai Y, Shen J, Zhu P, et al. The Nrf-2/HO-1 signaling axis: a ray of hope in cardiovascular diseases. Cardiol Res Pract. 2020;2020:5695723.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Li QY, Xu HY, Yang HJ. Effect of proinflammatory factors TNF-α, IL-1β, IL-6 on neuropathic pain. Zhongguo Zhong Yao Za Zhi. 2017;42:3709–12.

    PubMed  Google Scholar 

  24. Kelley N, Jeltema D, Duan Y, He Y. The NLRP3 inflammasome: an overview of mechanisms of activation and regulation. Int J Mol Sci. 2019;20(13):3328.

  25. Shi X, Yu W, Liu L, Liu W, Zhang X, Yang T, et al. Panax notoginseng saponins administration modulates pro-/anti-inflammatory factor expression and improves neurologic outcome following permanent MCAO in rats. Metab Brain Dis. 2017;32:221–33.

    Article  CAS  PubMed  Google Scholar 

  26. Chen X, Wang W, Liu X, Liu H, Sun H, Wang L, et al. Catalytic subunit of protein phosphatase 2A (PP2Ac) influences the meiosis initiation during spermatocyte meiosis prophase I. Reprod Sci. 2022;29(11):3201–3211.

  27. Jiang Y, Chen Y, Huang C, Xia A, Wang G, Liu S. Hyperbaric oxygen therapy improves neurological function via the p38-MAPK/CCL2 signaling pathway following traumatic brain injury. NeuroReport. 2021;32:1255–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Fan S, Liu X, Wang Y, Ren X, Liu Y, Dong Y, et al. Thymus quinquecostatus Celak. ameliorates cerebral ischemia-reperfusion injury via dual antioxidant actions: activating Keap1/Nrf2/HO-1 signaling pathway and directly scavenging ROS. Phytomedicine. 2021;91:153673.

  29. Mann U, Shiff B, Patel P. Reasons for worldwide decline in male fertility. Curr Opin Urol. 2020;30:296–301.

    Article  PubMed  Google Scholar 

  30. Sato H, Taketomi Y, Isogai Y, Miki Y, Yamamoto K, Masuda S, et al. Group III secreted phospholipase A2 regulates epididymal sperm maturation and fertility in mice. J Clin Invest. 2010;120:1400–14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Ansari MY, Ahmad N, Haqqi TM. Oxidative stress and inflammation in osteoarthritis pathogenesis: role of polyphenols. Biomed Pharmacother. 2020;129:110452.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Zhang P, Li T, Wu X, Nice EC, Huang C, Zhang Y. Oxidative stress and diabetes: antioxidative strategies. Front Med. 2020;14:583–600.

    Article  PubMed  Google Scholar 

  33. Takeshima T, Usui K, Mori K, Asai T, Yasuda K, Kuroda S, et al. Oxidative stress and male infertility. Reprod Med Biol. 2021;20:41–52.

    Article  CAS  PubMed  Google Scholar 

  34. Ommati MM, Li H, Jamshidzadeh A, Khoshghadam F, Retana-Márquez S, Lu Y, et al. The crucial role of oxidative stress in non-alcoholic fatty liver disease-induced male reproductive toxicity: the ameliorative effects of Iranian indigenous probiotics. Naunyn Schmiedebergs Arch Pharmacol. 2022;395:247–65.

    Article  CAS  PubMed  Google Scholar 

  35. Hu X, Ge X, Liang W, Shao Y, Jing J, Wang C, et al. Effects of saturated palmitic acid and omega-3 polyunsaturated fatty acids on Sertoli cell apoptosis. Syst Biol Reprod Med. 2018;64:368–80.

    Article  CAS  PubMed  Google Scholar 

  36. Guilherme A, Virbasius JV, Puri V, Czech MP. Adipocyte dysfunctions linking obesity to insulin resistance and type 2 diabetes. Nat Rev Mol Cell Biol. 2008;9:367–77.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Kahn BE, Brannigan RE. Obesity and male infertility. Curr Opin Urol. 2017;27:441–5.

    Article  PubMed  Google Scholar 

  38. Begic A, Dilic M. Evaluation of the occlusive arterial disease and diabetic angiopathy treatment effects by hyperbaric oxygenation. Med Arch. 2019;73:244–8.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Xie Y, Zhao QY, Li HY, Zhou X, Liu Y, Zhang H. Curcumin ameliorates cognitive deficits heavy ion irradiation-induced learning and memory deficits through enhancing of Nrf2 antioxidant signaling pathways. Pharmacol Biochem Behav. 2014;126:181–6.

    Article  CAS  PubMed  Google Scholar 

  40. Santini SJ, Cordone V, Falone S, Mijit M, Tatone C, Amicarelli F, Di Emidio G. Role of mitochondria in the oxidative stress induced by electromagnetic fields: focus on reproductive systems. Oxidative Medicine & Cellular Longevity. 2018;2018:5076271.

  41. Luo D, Zhang M, Su X, Liu L, Zhou X, Zhang X, et al. High fat diet impairs spermatogenesis by regulating glucose and lipid metabolism in Sertoli cells. Life Sci. 2020;257:118028.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

HBO treatment was performed at the in the Neurorehabilitation Department of Changzhou Second People’s Hospital. We thank all participants for their cooperation in the treatment process.

Funding

This study was supported by Changzhou Sci & Tech Program (20210110), the National Nature Science Foundation of China (81803498), and the Science Foundation of Nanjing Medical University Affiliated Changzhou Second People’s Hospital (2022K007).

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Jiaping Wang or Xia Chen.

Ethics declarations

Ethics Approval

The animal study was conducted according to Institutional Animal Care and Use Committee (IACUC) of Nanjing Medical University and approved by Changzhou No.2 People’s Hospital Ethics Committee.

Consent to Participate

Not applicable.

Consent for Publication

Not applicable.

Conflict of Interest

The authors declare no competing interests.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Liu, H., Wang, D., Ma, Y. et al. Hyperbaric Oxygen Therapy Ameliorates Sperm Parameters in Apolipoprotein E Knockout Mice Testes by Attenuating Oxidative Stress and Inflammation. Reprod. Sci. 30, 2252–2262 (2023). https://doi.org/10.1007/s43032-022-01158-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s43032-022-01158-9

Keywords

Navigation