Introduction
Male infertility is a growing concern worldwide, affecting approximately 15% of couples trying to conceive, with male factors contributing to about half of these cases. Among the various nutritional and environmental influences on male reproductive health, selenium—a trace mineral with potent antioxidant properties—has emerged as a key player. Research over the past decades has increasingly highlighted selenium's essential role in spermatogenesis, sperm quality, and overall fertility. Selenium deficiency has been linked to impaired sperm motility, morphology, and DNA integrity, while appropriate supplementation may offer protective and restorative benefits. This article delves into the biological mechanisms, scientific evidence from animal and human studies, potential benefits of supplementation, risks, and practical recommendations for incorporating selenium into strategies for addressing male infertility.
What is Selenium?
Selenium is an essential micronutrient found in soil, water, and various foods. It is incorporated into proteins as selenocysteine, the 21st amino acid, forming selenoproteins that perform critical biological functions. There are about 25 known selenoproteins in humans, many of which act as antioxidants, regulating thyroid hormone metabolism, immune function, and reproductive health. In the context of male reproduction, key selenoproteins include glutathione peroxidase 4 (GPX4), which is abundant in sperm and protects against oxidative damage, and selenoprotein P (SEPP1), which transports selenium to the testes.
Selenium's bioavailability varies based on its form: organic forms like selenomethionine (found in plants and animal tissues) are more readily absorbed than inorganic forms like selenite or selenate. The recommended daily allowance (RDA) for adults is 55 micrograms per day, but needs may increase in cases of deficiency or high oxidative stress, such as in infertility. Deficiency is common in regions with selenium-poor soil, affecting populations in parts of China, Europe, and New Zealand, and can exacerbate reproductive issues.
Overview of Male Infertility
Male infertility is typically diagnosed through semen analysis, revealing abnormalities in sperm count (oligospermia), motility (asthenospermia), morphology (teratospermia), or a combination (oligoasthenoteratozoospermia, or OAT). Oxidative stress—caused by an imbalance between reactive oxygen species (ROS) and antioxidants—is a major contributor, damaging sperm DNA, membranes, and proteins. Other factors include hormonal imbalances, varicocele, infections, lifestyle choices (e.g., smoking, poor diet), and environmental toxins.
In this landscape, selenium's antioxidant role becomes pivotal. It helps neutralize ROS, preserving sperm viability and function. Studies indicate that low selenium levels in seminal plasma correlate with reduced sperm quality and increased infertility risk, making it a target for intervention.
Biological Role of Selenium in Male Reproduction
Selenium influences male fertility through multiple mechanisms:
Antioxidant Defense
Selenium's primary role is as an antioxidant. GPX4, a selenium-dependent enzyme, reduces lipid hydroperoxides in sperm membranes, preventing oxidative damage that could lead to immotility or apoptosis. In the testes, selenium protects Leydig cells (responsible for testosterone production) and Sertoli cells (supporting spermatogenesis) from ROS-induced injury.
Spermatogenesis and Sperm Maturation
Selenium is essential for normal spermatogenesis—the process of sperm production. It supports chromatin condensation in sperm heads, ensuring DNA stability, and maintains the structural integrity of the sperm midpiece, which houses mitochondria for energy production. Selenoprotein P ensures selenium delivery to the testes, prioritizing reproductive tissues during deficiency.
Hormone Regulation
Selenium modulates testosterone biosynthesis via pathways like the extracellular-signal-regulated kinase (ERK) signaling and genes such as steroidogenic acute regulatory protein (StAR). Low selenium can disrupt thyroid function, indirectly affecting reproductive hormones.
Protection Against Toxins
Selenium counteracts environmental toxins like cadmium, nickel, and pesticides, which induce testicular damage. For instance, nano-selenium has shown promise in attenuating such toxicities in animal models.
Overall, selenium exhibits a U-shaped dose-response curve: optimal levels enhance fertility, while deficiency or excess can impair it.
Selenium Deficiency and Male Infertility
Selenium deficiency is linked to 20-40% of male infertility cases involving deficient sperm production. Low seminal selenium correlates with poor sperm quality, higher oxidative stress markers, and reduced GPX activity. In deficient individuals, sperm may exhibit flagellar defects, midpiece abnormalities, and increased DNA fragmentation, leading to subfertility.
Geographic variations play a role; in selenium-poor areas, supplementation could be particularly beneficial. Biomarkers like seminal GPX4 levels may help diagnose deficiency-related infertility.
Evidence from Animal Studies
Animal research provides robust evidence for selenium's role. In rats, selenium deficiency alters testicular morphology, reduces GPX activity, and impairs testosterone production. Mice with selenium deficiency show higher abnormal sperm ratios (up to 49.6%) and chromosome abnormalities in spermatocytes.
In goats and rams, maternal or dietary selenium (0.5-2.0 mg/kg) improves testicular histomorphology, semen volume, motility, and antioxidant status. Boars supplemented with organic selenium produce 23% more semen doses weekly. Studies in buffalo bulls, rabbits, and dogs also report enhanced sperm parameters and fertility with selenium, often synergistically with vitamin E.
Protective effects against toxins are evident: selenium mitigates damage from varicocele, nickel, bisphenol A, and pesticides in rats and mice.
Evidence from Human Studies
Human studies, though fewer and sometimes inconsistent, support selenium's benefits. In infertile men, GPX4 levels are reduced by up to 90%, correlating with poor motility and integrity.
A study of 690 infertile men with asthenoteratospermia found that 200 μg selenium plus 400 IU vitamin E for 100 days improved motility and morphology in 52.6%, leading to 10.8% spontaneous pregnancies. Another trial with 468 OAT patients showed 200 μg selenium (alone or with N-acetyl-cysteine) for 26 weeks enhanced sperm count, motility, morphology, and hormone levels.
In 20 men with autoimmune thyroiditis, 83 μg selenium for six months boosted concentration, motility, morphology, and reduced DNA fragmentation. Meta-analyses confirm improvements in sperm parameters with 100-300 μg/day for 3-11 months. However, a large trial (174 couples) found no benefits from combined antioxidants including selenium, highlighting study design variations.
Synergies with vitamin E, CoQ10, or zinc amplify effects.
Selenium Supplementation: Benefits and Dosages
Supplementation (100-300 μg/day) can improve sperm motility, count, and morphology, especially in deficient individuals. Benefits are more pronounced in idiopathic infertility or post-varicocelectomy. Duration typically spans 3-6 months, aligning with the 74-day sperm cycle.
Organic forms are preferred for better absorption. Combined with antioxidants like vitamin E (400 IU), it enhances outcomes, including pregnancy rates.
Potential Risks and Side Effects
While beneficial, excess selenium (>400 μg/day) can impair sperm quality and cause selenosis (nausea, hair loss). High intake may disrupt ROS balance needed for sperm capacitation. In healthy men without deficiency, supplementation may yield no benefits. Monitoring levels is crucial to avoid toxicity.
Dietary Sources and Recommendations
Rich sources include Brazil nuts (one nut provides ~68-96 μg), seafood, meat, eggs, and grains. For infertility, aim for RDA via diet; supplement if deficient, under medical supervision. Testing seminal or blood selenium can guide personalization.
Conclusion
Selenium is indispensable for male fertility, safeguarding against oxidative stress and supporting spermatogenesis. While animal studies strongly affirm its role, human evidence, though promising, calls for more rigorous trials to optimize dosages and identify responders. Integrating selenium into fertility management—through diet or targeted supplementation—could offer a safe, cost-effective approach, particularly when combined with other antioxidants. Consult healthcare professionals for tailored advice, as selenium's benefits shine brightest in the context of deficiency. Future research may unlock personalized therapies, potentially transforming outcomes for millions affected by male infertility.