Impact of hypoxia on male reproductive functions

• Published in: Molecular and cellular biochemistry 2023-04, Vol.478 (4), p.875-885
• Main Authors: Oyedokun, P. A., Akhigbe, R. E., Ajayi, L. O., Ajayi, A. F.
• Format: Article
• Language: English
• Subjects: Antioxidants; Antioxidants - pharmacology; Autophagy; Biochemistry; Biomedical and Life Sciences; Calcium channels; Calcium channels (L-type); Calcium channels (voltage-gated); Cancer Research; Canonical forms; Cardiology; Channel gating; Chronic exposure; DNA methylation; Enzymes; Erectile dysfunction; Fertility; Humans; Hypothalamus; Hypoxia; Impotence; Life Sciences; Male; Males; Medical Biochemistry; Oxidative Stress; Penis; Pituitary; Semen - metabolism; Signaling; Sperm; Spermatogenesis; Spermatogenesis - physiology; Steroidogenesis; Testes; Testis - metabolism; Testosterone; Testosterone - pharmacology; Transforming growth factor-b1; Vascular endothelial growth factor
• ISSN: 0300-8177; 1573-4919
• DOI: 10.1007/s11010-022-04559-1

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.