{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T15:24:04Z","timestamp":1791905044426,"version":"4.3.4"},"reference-count":61,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2025,3,19]],"date-time":"2025-03-19T00:00:00Z","timestamp":1742342400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2021YFD1600201"],"award-info":[{"award-number":["2021YFD1600201"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Viral infections of the reproductive tract and testis in male yaks, often resulting from natural mating under grazing conditions, can lead to infertility due to Leydig cell (LC) apoptosis, immune activation, oxidative stress, and reduced testosterone production. Spermidine (SPD), a potential therapeutic agent with antioxidant and anti-aging properties, might alleviate oxidant stress, immune response, and virus infection caused by apoptosis. In this study, firstly testicular Leydig cells of yak were induced with Poly(I:C), the pathogen-associated molecular pattern of the dsRNA virus, as a pathogenic model at the cellular level. Secondly, immune response, apoptosis, oxidative stress, and testosterone synthesis were measured in LC with or without SPD culture medium. Finally, transcriptomic sequencing was utilized to investigate the molecular mechanisms underlying the protective effects of SPD. These results suggested Poly(I:C) damaged the function of Leydig cells, significantly decreased the concentration of testosterone, and induced immune response, oxidative stress, and cell apoptosis, while SPD significantly alleviated the immune response and oxidative stress, and then significantly inhibited cell apoptosis and restores testosterone production in LCs. Transcriptomic analysis revealed that SPD significantly alleviates inflammation and apoptosis induced by Poly(I:C), reducing immune response and cellular damage through the regulation of several key gene expressions. These findings suggest SPD has the potential ability to mitigate Poly(I:C)-induced immune response, oxidative stress, and apoptosis, and then restore testosterone production in Leydig cells, offering a promising strategy to protect and enhance male yak fertility after infection with dsRNA virus.<\/jats:p>","DOI":"10.3390\/ijms26062753","type":"journal-article","created":{"date-parts":[[2025,3,19]],"date-time":"2025-03-19T06:10:53Z","timestamp":1742364653000},"page":"2753","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Spermidine as a Potential Protective Agents Against Poly(I:C)-Induced Immune Response, Oxidative Stress, Apoptosis, and Testosterone Decrease in Yak Leydig Cells"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-7141-9898","authenticated-orcid":false,"given":"Yujun","family":"Tang","sequence":"first","affiliation":[{"name":"College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Li","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yutian","family":"Zeng","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cuiting","family":"Yang","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Run","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arab Khan","family":"Lund","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, China"},{"name":"Faculty of Animal Production and Technology, Shaheed Benazir Bhutto University of Veterinary and Animal Science, Sakrand 67210, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, China"},{"name":"Key Laboratory of Livestock and Poultry Multi-Omics, Ministry of Agriculture and Rural Affairs, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, China"},{"name":"Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Leisegang, K., and Henkel, R. 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