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Impact of hypoxia on male reproductive functions

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Abstract

Male reproductive functions, which include testicular steroidogenesis, spermatogenesis, and sexual/erectile functions are key in male fertility, but may be adversely altered by several factors, including hypoxia. This review demonstrates the impact of hypoxia on male reproductive functions. Acute exposure to hypoxia promotes testosterone production via stimulation of autophagy and upregulation of steroidogenic enzymes and voltage-gated L-type calcium channel, nonetheless, chronic exposure to hypoxia impairs steroidogenesis via suppression of the hypothalamic–pituitary–testicular axis. Also, hypoxia distorts spermatogenesis and reduces sperm count, motility, and normal forms via upregulation of VEGF and oxidative stress-sensitive signaling. Furthermore, hypoxia induces sexual and erectile dysfunction via a testosterone-dependent downregulation of NO/cGMP signaling and upregulation of PGE1/TGFβ1-driven penile endothelial dysfunction. Notably, hypoxia programs male sexual function and spermatogenesis/sperm quality via feminization and demasculinization of males and oxidative stress-mediated alteration in sperm DNA methylation. Since oxidative stress plays a central role in hypoxia-induced male reproductive dysfunction, studies exploring the effects of antioxidants and upregulation of transcription of antioxidants on hypoxia-induced male reproductive dysfunction are recommended.

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Authors and Affiliations

  1. Anchor Reproductive Physiology and Bioinformatics Research Unit, Department of Physiology, Ladoke Akintola University of Technology, Ogbomoso, Oyo, Nigeria

    P. A. Oyedokun, R. E. Akhigbe & A. F. Ajayi

  2. Reproductive Biology and Toxicology Research Laboratory, Oasis of Grace Hospital, Osogbo, Osun, Nigeria

    R. E. Akhigbe

  3. Department of Biochemistry, Ladoke Akintola University of Technology, Ogbomoso, Oyo, Nigeria

    L. O. Ajayi

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  3. L. O. Ajayi
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  4. A. F. Ajayi
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Authors’ contributions Conceptualization and study design: ARE Contribution of reagents/materials: OPA, ARE, ALO, AAF Writing of first draft: OPA, ARE, ALO, AAF Revision of the first draft: All authors Approval for submission and publication: All authors

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Oyedokun, P.A., Akhigbe, R.E., Ajayi, L.O. et al. Impact of hypoxia on male reproductive functions. Mol Cell Biochem 478, 875–885 (2023). https://doi.org/10.1007/s11010-022-04559-1

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