{"title":"Effects of L-carnitine over-supplementation on spermatogenesis and sperm function in healthy NMRI mice","authors":"Mitra Jabarineitapeh , Nushin Naderi , Marziyeh Tavalaee , Mohammad Hossein Nasr-Esfahani","doi":"10.1016/j.tice.2025.103014","DOIUrl":null,"url":null,"abstract":"<div><div>L-carnitine (LC) plays a key role in lipid metabolism by transporting fatty acids from the cytosol into mitochondria for energy production. Beyond its metabolic function, LC exhibits significant antioxidant, anti-cytokine, and anti-apoptotic properties, contributing to cellular protection. This study investigates the potential adverse effects of four weeks of LC supplementation (20, 100, and 500 mg/kg body weight, n = 10) on spermatogenesis and sperm function in healthy NMRI male mice. Sperm parameters—motility, concentration, and morphology—were assessed alongside sperm and testicular oxidative status. Sperm chromatin and DNA integrity were evaluated through histone persistence (Aniline Blue staining), protamine deficiency (CMA3 staining), and DNA fragmentation (Acridine Orange staining). Pregnancy outcomes were also investigated. After four weeks, the LC500 group exhibited significantly higher liver weight than the controls. However, sperm parameters, reactive oxygen species (ROS) production, lipid peroxidation, and testicular malondialdehyde and total antioxidant capacity levels showed no significant differences among groups. Notably, the LC500 group demonstrated a significant decline in sperm DNA and chromatin integrity (P < 0.05). Alongside, liver sections from LC500-treated mice showed a marked increase in lipid droplets, while controls maintained normal hepatic morphology. Despite these alterations, male fertility indices remained unchanged. Our findings suggest that while LC is essential for metabolism, over-supplementation may compromise male fertility by inducing sperm chromatin damage and DNA fragmentation. Furthermore, high-dose LC intake may contribute to inflammation and non-alcoholic fatty liver disease (NAFLD), emphasizing the need for cautious LC supplementation to safeguard reproductive health.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"96 ","pages":"Article 103014"},"PeriodicalIF":2.7000,"publicationDate":"2025-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Tissue & cell","FirstCategoryId":"99","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0040816625002940","RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ANATOMY & MORPHOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
L-carnitine (LC) plays a key role in lipid metabolism by transporting fatty acids from the cytosol into mitochondria for energy production. Beyond its metabolic function, LC exhibits significant antioxidant, anti-cytokine, and anti-apoptotic properties, contributing to cellular protection. This study investigates the potential adverse effects of four weeks of LC supplementation (20, 100, and 500 mg/kg body weight, n = 10) on spermatogenesis and sperm function in healthy NMRI male mice. Sperm parameters—motility, concentration, and morphology—were assessed alongside sperm and testicular oxidative status. Sperm chromatin and DNA integrity were evaluated through histone persistence (Aniline Blue staining), protamine deficiency (CMA3 staining), and DNA fragmentation (Acridine Orange staining). Pregnancy outcomes were also investigated. After four weeks, the LC500 group exhibited significantly higher liver weight than the controls. However, sperm parameters, reactive oxygen species (ROS) production, lipid peroxidation, and testicular malondialdehyde and total antioxidant capacity levels showed no significant differences among groups. Notably, the LC500 group demonstrated a significant decline in sperm DNA and chromatin integrity (P < 0.05). Alongside, liver sections from LC500-treated mice showed a marked increase in lipid droplets, while controls maintained normal hepatic morphology. Despite these alterations, male fertility indices remained unchanged. Our findings suggest that while LC is essential for metabolism, over-supplementation may compromise male fertility by inducing sperm chromatin damage and DNA fragmentation. Furthermore, high-dose LC intake may contribute to inflammation and non-alcoholic fatty liver disease (NAFLD), emphasizing the need for cautious LC supplementation to safeguard reproductive health.
期刊介绍:
Tissue and Cell is devoted to original research on the organization of cells, subcellular and extracellular components at all levels, including the grouping and interrelations of cells in tissues and organs. The journal encourages submission of ultrastructural studies that provide novel insights into structure, function and physiology of cells and tissues, in health and disease. Bioengineering and stem cells studies focused on the description of morphological and/or histological data are also welcomed.
Studies investigating the effect of compounds and/or substances on structure of cells and tissues are generally outside the scope of this journal. For consideration, studies should contain a clear rationale on the use of (a) given substance(s), have a compelling morphological and structural focus and present novel incremental findings from previous literature.