Selenium as a Modulator of Reproductive Immunity: Molecular Insights and Translational Potential in Livestock

The periparturient period represents a critical window of vulnerability in livestock reproduction. Additionally, reproductive performance is often compromised due to a weakened immune system and high oxidative stress. Selenium, an essential micronutrient, emerges as a key element with dual roles in antioxidant defence and immune modulation, making it a cornerstone in maintaining reproductive health in livestock. Selenium exerts its protective effects through incorporation into selenoproteins such as glutathione peroxidase (GPx), which downregulate oxidative stress, support cellular integrity, and regulate inflammation in reproductive tissues. During the periparturient period, selenium deficiency is associated with increased production of β-hydroxybutyric acid (BHBA) and non-esterified fatty acids (NEFA), responsible for triggering lipid mobilisation and activation of the NF-κB (Nuclear Factor kappa-light-chain-enhancer of activated B cells) signalling pathway. This leads to overexpression of pro-inflammatory genes, resulting in uterine infections, mastitis, and other reproductive disorders. Selenium supplementation in organic or nano forms plays a potential role in countering these effects by activating the Nrf2 (Nuclear factor erythroid 2) pathway, boosting antioxidant enzymes, and suppressing the NF-κB pathway. In females, selenium enhances endometrial epithelial repair, hormone regulation, and immune tolerance by regulating the NF-κB signalling pathway. In males, combined supplementation of selenium with vitamin E improves sperm quality, motility, and testosterone levels while preventing lipid peroxidation in spermatozoa. At the epigenetic level, selenium influences histone acetylation to regulate transcription of inflammatory genes such as COX-2 and TNF-α. Recent insights into the role of selenium receptors (LRP8) in ovarian follicular development highlight the applications of selenium in fertility regulation. The efficacy of selenium is highly influenced by its form, dosage, animal species, and physiological state. This review emphasises the need for large-scale, species-specific research trials, nanodelivery strategies, and omics-based biomarkers to improve selenium supplementation strategies and dose rate. Selenium holds significant translational potential in veterinary reproduction, playing a preventative and therapeutic role against reproductive immunopathologies in livestock.