Academic Journal
TRPM8 activation by sustained-release menthol mitigates exertional heatstroke-induced testicular injury and sperm ultrastructural damage in rats.
| Τίτλος: | TRPM8 activation by sustained-release menthol mitigates exertional heatstroke-induced testicular injury and sperm ultrastructural damage in rats. |
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| Συγγραφείς: | Ruan T; School of Medicine, College of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan. Electronic address: 092810@mail.fju.edu.tw., Chao CM; Department of Intensive Care Medicine, Chi Mei Hospital, Liouying, Tainan, Taiwan; Department of Dental Laboratory Technology, Min-Hwei College of Health Care Management, Tainan, Taiwan. Electronic address: 870958@chimei.org.tw., Shen CM; School of Medicine, College of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan; Department of Pediatrics, Cathay General Hospital, Taipei, Taiwan. Electronic address: cgh09218@cgh.org.tw., Hsieh KL; Division of Urology, Department of Surgery, Chi Mei Medical Center, Tainan, Taiwan; Department of Environmental and Occupational Health, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Department of Medical Laboratory Science and Biotechnology, College of Medicine and Life Science, Chung Hwa University of Medical Technology, Tainan, Taiwan. Electronic address: 990707@chimei.org.tw., Chen TH; Department of Medical Research, Chi Mei Medical Center, Tainan, Taiwan; Center for General Education, Southern Taiwan University of Science and Technology, Tainan, Taiwan. Electronic address: B50333@chimei.org.tw., Tang LY; Department of Medical Research, Chi Mei Medical Center, Tainan, Taiwan. Electronic address: B408J4@chimei.org.tw., Tan TH; Department of Emergency Medicine, Chi Mei Medical Center, Tainan, Taiwan; School of Medicine, Chung Shan Medical University, Taichung, Taiwan. Electronic address: 990916@chimei.org.tw., Lin YJ; Research Center for Applied Sciences, Academia Sinica, Taipei, Taiwan. Electronic address: linyujung@gate.sinica.edu.tw., Chang CP; Department of Medical Research, Chi Mei Medical Center, Tainan, Taiwan. Electronic address: a50831@chimei.org.tw. |
| Πηγή: | Life sciences [Life Sci] 2026 Oct 15; Vol. 403, pp. 124606. Date of Electronic Publication: 2026 Jul 28. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Elsevier Country of Publication: Netherlands NLM ID: 0375521 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1879-0631 (Electronic) Linking ISSN: 00243205 NLM ISO Abbreviation: Life Sci Subsets: MEDLINE |
| Imprint Name(s): | Publication: <2008->: Amsterdam : Elsevier Original Publication: Oxford; Elmsford, N. Y. [etc.] Pergamon Press. |
| Ιατρικοί όροι (MeSH): | Menthol*/pharmacology , Menthol*/administration & dosage , TRPM Cation Channels*/metabolism , Heat Stroke*/complications , Heat Stroke*/drug therapy , Heat Stroke*/metabolism , Heat Stroke*/pathology , Testis*/drug effects , Testis*/metabolism , Testis*/pathology , Testis*/injuries , Spermatozoa*/ultrastructure , Spermatozoa*/drug effects , Spermatozoa*/pathology , Spermatozoa*/metabolism, Apoptosis/drug effects ; Testosterone/blood ; Animals ; Male ; Rats, Wistar ; Rats ; Scrotum ; Hyperthermia ; Claudins ; Zonula Occludens-1 Protein |
| Περίληψη: | Aims: Exertional heatstroke (EHS) can induce marked scrotal hyperthermia and impair male reproductive integrity. This study tested whether sustained-release menthol protects against EHS-induced testicular and genitourinary injury via transient receptor potential melastatin 8 (TRPM8) activation. Materials and Methods: Adult male Wistar rats received sustained-release menthol gel (30 mg·kg-1, subcutaneously) or vehicle for 2 weeks before EHS induction (36 °C, 50% relative humidity; approximately 52 min of treadmill running). Some rats received AMTB, a selective TRPM8 antagonist. Scrotal temperature change (ΔTscrotal) and circulating hormones were measured, and genitourinary tissues were examined on Day 3 after EHS. Blood-testis barrier proteins (claudin-11 and ZO-1), TRPM8, and apoptosis of Sertoli and Leydig cells were quantified by four-colour immunofluorescence, and sperm ultrastructure was assessed by scanning and transmission electron microscopy. Key Findings: Vehicle-treated EHS rats showed marked scrotal hyperthermia (ΔTscrotal: 6.5 °C vs 0.75 °C in controls), reduced testosterone with elevated luteinizing hormone, sperm dysmorphology, and multisite genitourinary injury. EHS reduced claudin-11/ZO-1 and TRPM8 in seminiferous tubules and increased Sertoli/Leydig cell apoptosis. Electron microscopy revealed sperm head deformation, head-neck discontinuity, mitochondrial sheath disruption in the midpiece, and fissures/perforations along the principal piece. Menthol pretreatment attenuated scrotal hyperthermia (ΔTscrotal: 2.6 °C), improved testosterone, reduced Sertoli and Leydig cell apoptosis, and alleviated histological and ultrastructural injury. These benefits were blunted by AMTB, supporting TRPM8-dependent protection. Significance: Sustained-release menthol mitigates EHS-induced male reproductive and genitourinary injury in rats, at least partly through TRPM8 activation. TRPM8 may represent a potential prophylactic target for reducing heat-related reproductive damage. (Copyright © 2026 The Authors. Published by Elsevier Inc. All rights reserved.) |
| Competing Interests: | Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. |
| Σχόλια: | Erratum in: Life Sci. 2026 Sep 26:124707. doi: 10.1016/j.lfs.2026.124707.. (PMID: 42791148) |
| Contributed Indexing: | Keywords: Blood-testis barrier; Exertional heatstroke; Menthol; Scrotal hyperthermia; Sperm ultrastructure; TRPM8 |
| Substance Nomenclature: | 1490-04-6 (Menthol) 0 (TRPM Cation Channels) 0 (Trpm8 protein, rat) 0 (Cldn11 protein, rat) 3XMK78S47O (Testosterone) 0 (Tjp1 protein, rat) 0 (Claudins) 0 (Zonula Occludens-1 Protein) |
| Entry Date(s): | Date Created: 20260728 Date Completed: 20260826 Latest Revision: 20260925 |
| Update Code: | 20260926 |
| DOI: | 10.1016/j.lfs.2026.124606 |
| PMID: | 42521118 |
| Βάση Δεδομένων: | MEDLINE |
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