In dairy goats and mice, melatonin improved sperm quality, preserved testicular structure, and restored testosterone levels. Modulation of arginine and tryptophan metabolism emerges as a key mechanism supporting reproductive resilience in heat-stressed livestock.
Heat stress is a major environmental factor that impairs male fertility in livestock, especially during breeding seasons with high temperatures. Elevated body and scrotal temperatures disrupt spermatogenesis, reduce sperm density and motility, and increase abnormal morphology. At the cellular level, heat stress damages testicular cells, compromises the blood–testis barrier, and suppresses steroid hormone synthesis. Oxidative stress and inflammation drive much of this dysfunction, often accompanied by imbalances in testosterone, FSH, and LH. Although melatonin is known for its antioxidant and anti-inflammatory effects, its potential role in metabolic regulation—particularly via amino acid pathways—remains unclear. Arginine and tryptophan are essential for spermatogenesis and hormone regulation, yet whether melatonin protects fertility by modulating these pathways under heat stress has not been fully investigated.
A study (DOI: 10.48130/animadv-0025-0041) published in Animal Advances on 11 February 2026 by Bao-hua Ma’s & Sha Peng’s team, Northwest A&F University, reveals that targeting melatonin and amino acid metabolism can effectively protect male fertility against heat stress.
Using complementary livestock and rodent models plus multi-omics profiling, researchers tested whether melatonin could protect male reproduction during heat stress by implanting melatonin in dairy goats before summer heat exposure and, in parallel, treating heat-stressed male mice with melatonin or the amino acids arginine/tryptophan while measuring semen traits, systemic inflammation/oxidative status and hormones (ELISA), serum metabolism (untargeted LC–MS with PLS-DA/OPLS-DA and KEGG enrichment), targeted amino-acid quantification (LC–MS/MS with isotope standards), and testicular molecular/pathology endpoints (RT-qPCR, H&E, TUNEL, immunohistochemistry, Western blotting, and immunofluorescence for BTB proteins). In goats, heat stress elevated respiratory rate and rectal temperature without changing scrotal temperature, and it sharply reduced sperm density, motility, and viability while worsening kinematics (lower VSL and STR) and increasing abnormal morphology; melatonin lowered rectal temperature toward control levels and significantly improved sperm quality and motion, with no changes in semen volume or pH. Consistent with these functional gains, heat stress increased pro-inflammatory cytokines (IL-1β, IL-2, IL-6, TNF-α) and ROS while decreasing antioxidant capacity (GSH, T-AOC) and disrupting the reproductive axis (lower testosterone with higher FSH/LH); melatonin raised circulating melatonin sustainably and reversed inflammatory, oxidative, and hormonal disturbances. Metabolomics showed clear separation of control vs heat-stressed serum profiles and dozens of differential metabolites, indicating global metabolic reprogramming; adding melatonin shifted the metabolome again, with altered compounds enriched in amino-acid pathways—especially tryptophan metabolism. Targeted assays confirmed that heat stress reduced serum arginine and tryptophan (and related metabolites such as ornithine/citrulline and kynurenine), whereas melatonin partially restored them. In mice, heat stress suppressed testicular ARG1 and reduced BTB integrity, but melatonin restored ARG1 and upregulated tryptophan-pathway enzymes (TPH1, KYNU). Supplementing arginine or tryptophan alone improved organ indices and sperm traits, repaired seminiferous-tubule and epididymal pathology, reduced Sertoli-cell apoptosis and local inflammatory signals, restored occludin and ZO-1 expression/localization at the BTB, and reactivated steroidogenesis (higher testosterone with recovery of StAR/CYP11A1 and related genes), demonstrating that melatonin’s protection is closely tied to arginine/tryptophan metabolic control under heat stress.
In conclusion, heat stress poses a serious threat to male fertility and livestock productivity under a warming climate. This study demonstrates that melatonin enhances reproductive resilience by reducing oxidative stress and inflammation, stabilizing hormonal balance, and restoring amino acid metabolism. Targeting arginine and tryptophan pathways offers a promising nutritional strategy to safeguard fertility and sustain breeding efficiency in heat-prone environments.
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References
DOI
10.48130/animadv-0025-0041
Original Source URL
https://doi.org/10.48130/animadv-0025-0041
Funding information
This work was supported by the Grants from the National Key Research and Development Program of China [2022YFD1300200], Central Government Guidance Fund for Local Science and Technology Development Program of Qinghai Province (2025-ZY-069), Horizontal Research Funding from Ningbo Second Hormone Factory (TG20250168).
About Animal Advances
Animal Advances (e-ISSN 3065-7660) is an open-access journal which published by Maximum Academic Press in partnership with Nanjing Agricultural University. The journal is dedicated to delivering cutting-edge discoveries and progress in animal sciences to a diverse audience, encompassing scholars, academicians, and practitioners in the industry.