Mechanistic Insights into the Effects of Essential Micronutrients on Spermatogenesis: Focus on Selenium, Folate, Vitamin C, Vitamin E and Zinc
Authors
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Mohammad Hossein Ebrahimi
Environmental and Occupational Health Research Center, Shahroud University of Medical Sciences, Shahroud, Iran.
https://orcid.org/0000-0002-1725-861X
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Mina Darand
Cardiovascular Research Center, Rajaie Cardiovascular Institute, Tehran, Iran.
https://orcid.org/0000-0003-2636-0963
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Masoumeh Atefi
Environmental and Occupational Health Research Center, Shahroud University of Medical Sciences, Shahroud, Iran.
https://orcid.org/0000-0003-3984-166X
DOI:
https://doi.org/10.22100/ijhs.v12i5.1609Keywords:
Male infertility, Spermatogenesis, Micronutrients, Oxidative stress, Selenium, Zinc, Folate, Vitamins C and E, DNA methylationAbstract
Background: Male infertility and impaired spermatogenesis remain significant reproductive health concerns worldwide. Oxidative stress, deoxyribonucleic acid (DNA) damage, disrupted cellular metabolism, and epigenetic dysregulation are among the key mechanisms implicated in poor sperm quality. Specific micronutrients—including selenium, zinc, folate, vitamin C, and vitamin E—have been proposed to modulate spermatogenesis through antioxidant activity, regulation of gene expression, and maintenance of cellular integrity. This narrative review aims to synthesize recent evidence on the biological pathways by which these micronutrients interact with spermatogenic processes.
Methods: This study was a narrative review of the literature. Data were collected from recent mechanistic and clinical studies investigating the roles of selenium, zinc, folate, vitamin C, and vitamin E in male reproductive health. The primary outcomes were antioxidant defense, mitochondrial function, DNA synthesis and methylation, genomic integrity, and sperm structural stability. The biological pathways and clinical supplementation outcomes were systematically synthesized and evaluated.
Results: Selenium and zinc were found to contribute to antioxidant defense, mitochondrial function, and sperm structural stability through selenoproteins and zinc-dependent enzymes. Folate played a central role in DNA synthesis and methylation, which are critical for germ cell proliferation and epigenetic programming. Vitamins C and E protect germ cells and sperm membranes from oxidative damage through their antioxidant properties. Although clinical supplementation studies reported heterogeneous outcomes, mechanistic evidence consistently supported essential roles for these micronutrients in maintaining the testicular microenvironment, genomic integrity, and functional competence of spermatozoa.
Conclusion: Our review revealed that selenium, zinc, folate, and vitamins C and E exert essential biological effects on spermatogenesis through antioxidant activity, epigenetic regulation, and cellular integrity maintenance. However, clinical translation remains limited due to heterogeneous supplementation outcomes. Further well-designed studies are required to translate mechanistic insights into targeted nutritional interventions for male infertility.
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