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Carbamazepine (CBZ), a common anticonvulsant medication, can influence lipid metabolism and profiles, potentially impacting Leydig cell function and testosterone levels. Understanding this interplay is crucial to optimize treatment strategies for individuals requiring CBZ therapy while mitigating any adverse effects on male reproductive health. This study focuses on evaluating the effects of selected CBZ concentrations on the lipid homeostasis of BLTK-1 murine Leydig cells. By employing liquid chromatography-mass spectrometry (LC-MS) and gas chromatography-mass spectrometry (GC-MS), we aimed to uncover the specific changes in lipid profiles induced by CBZ exposure (25 and 200 \u03bcM). FA analysis demonstrated a significant decrease in FA 22:6 n-3 with increasing CBZ concentration and an increase in the n-6\/n-3 ratio. Furthermore, changes in the lipidome, particularly in lipid species belonging to phosphatidylethanolamine (PE), phosphatidylcholine (PC), phosphatidylglycerol (PG), and sphingomyelin (SM) classes were observed. PE and PC lipid species were significantly elevated in Leydig cells exposed to 200 \u03bcM CBZ, whereas PG and SM species were downregulated. CBZ treatment significantly altered the Leydig cell phospholipidome, suggesting specific phospholipids such as PG 40:4, PG 34:1, PC O-32:1, PC 32:2, and PE P-38:6, which exhibited the lowest p-values, as potential biomarkers for clinical assessment of CBZ's impact on Leydig cells. These findings underscore the intricate relationship between CBZ exposure and alterations in lipid profiles, offering potential insights for monitoring and mitigating the drug's effects on male reproductive health.<\/jats:p>\n                  <jats:p\/>","DOI":"10.1039\/d4mo00221k","type":"journal-article","created":{"date-parts":[[2025,2,4]],"date-time":"2025-02-04T10:11:22Z","timestamp":1738663882000},"page":"202-214","update-policy":"https:\/\/doi.org\/10.1039\/rsc_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Unmasking the lipid landscape: carbamazepine induces alterations in Leydig cell lipidome"],"prefix":"10.1093","volume":"21","author":[{"given":"In\u00eas","family":"Nobre","sequence":"first","affiliation":[{"name":"Servi\u00e7o Patologia Cl\u00ednica, ULS Coimbra c , 3004-561 Coimbra, Portugal"},{"name":"Mass Spectrometry Centre, LAQV-REQUIMTE, Department of Chemistry, University of Aveiro b , Santiago University Campus, 3810-193 Aveiro Portugal"},{"name":"CESAM-Centre for Environmental and Marine Studies, Department of Chemistry, University of Aveiro a , Santiago University Campus, 3810-193 Aveiro Portugal"}]},{"given":"In\u00eas M S","family":"Guerra","sequence":"additional","affiliation":[{"name":"Mass Spectrometry Centre, LAQV-REQUIMTE, Department of Chemistry, University of Aveiro b , Santiago University Campus, 3810-193 Aveiro Portugal"},{"name":"CESAM-Centre for Environmental and Marine Studies, Department of Chemistry, University of Aveiro a , Santiago University Campus, 3810-193 Aveiro Portugal"}]},{"given":"Marisa","family":"Pinho","sequence":"additional","affiliation":[{"name":"CESAM-Centre for Environmental and Marine Studies, Department of Chemistry, University of Aveiro a , Santiago University Campus, 3810-193 Aveiro Portugal"}]},{"given":"Ana D","family":"Martins","sequence":"additional","affiliation":[{"name":"LAQV-REQUIMTE and Department of Chemistry, University of Aveiro d , 3810-193 Aveiro, Portugal"},{"name":"Mass Spectrometry Centre, LAQV-REQUIMTE, Department of Chemistry, University of Aveiro b , Santiago University Campus, 3810-193 Aveiro Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9282-9013","authenticated-orcid":false,"given":"Laura","family":"Goracci","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Biology and Biotechnology, University of Perugia e , 06123 Perugia, Italy"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0474-0922","authenticated-orcid":false,"given":"Stefano","family":"Bonciarelli","sequence":"additional","affiliation":[{"name":"Molecular Discovery Ltd. f , Hertfordshire WD6 4PJ, UK"}]},{"given":"T\u00e2nia","family":"Melo","sequence":"additional","affiliation":[{"name":"Mass Spectrometry Centre, LAQV-REQUIMTE, Department of Chemistry, University of Aveiro b , Santiago University Campus, 3810-193 Aveiro Portugal"},{"name":"CESAM-Centre for Environmental and Marine Studies, Department of Chemistry, University of Aveiro a , Santiago University Campus, 3810-193 Aveiro Portugal"}]},{"given":"Pedro","family":"Domingues","sequence":"additional","affiliation":[{"name":"Mass Spectrometry Centre, LAQV-REQUIMTE, Department of Chemistry, University of Aveiro b , Santiago University Campus, 3810-193 Aveiro Portugal"}]},{"given":"Artur","family":"Paiva","sequence":"additional","affiliation":[{"name":"Ci\u00eancias Biom\u00e9dicas Laboratoriais, ESTESC \u2013 Coimbra Health School, Instituto Polit\u00e9cnico de Coimbra i , 3046-854 Coimbra, Portugal"},{"name":"Faculty of Medicine, Coimbra Institute for Clinical and Biomedical Research (iCBR), University of Coimbra h , 3000-370 Coimbra, Portugal"},{"name":"Unidade de Gest\u00e3o Operacional em Citometria, Centro Hospitalar e Universit\u00e1rio de Coimbra (CHUC) g , 3004-561 Coimbra, Portugal"}]},{"given":"Pedro F","family":"Oliveira","sequence":"additional","affiliation":[{"name":"LAQV-REQUIMTE and Department of Chemistry, University of Aveiro d , 3810-193 Aveiro, Portugal"},{"name":"Mass Spectrometry Centre, LAQV-REQUIMTE, Department of Chemistry, University of Aveiro b , Santiago University Campus, 3810-193 Aveiro Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5357-3601","authenticated-orcid":false,"given":"M Ros\u00e1rio","family":"Domingues","sequence":"additional","affiliation":[{"name":"Mass Spectrometry Centre, LAQV-REQUIMTE, Department of Chemistry, University of Aveiro b , Santiago University Campus, 3810-193 Aveiro Portugal"},{"name":"CESAM-Centre for Environmental and Marine Studies, Department of Chemistry, University of Aveiro a , Santiago University Campus, 3810-193 Aveiro Portugal"}]}],"member":"286","published-online":{"date-parts":[[2025,2,4]]},"reference":[{"key":"2026010813060639700_cit1","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1093\/biolre\/ioy059","article-title":"Leydig cells: formation, function, and regulation","volume":"99","author":"Zirkin","year":"2018","journal-title":"Biol. 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Biol."},{"key":"2026010813060639700_cit5","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1093\/pnasnexus\/pgac215","article-title":"Functional metabolite reserves and lipid homeostasis revealed by the MA-10 Leydig cell metabolome","volume":"1","author":"Koganti","year":"2022","journal-title":"PNAS Nexus"},{"issue":"2554","key":"2026010813060639700_cit6","first-page":"1","article-title":"Dynamic Remodeling of Membranes and Their Lipids during Acute Hormone-Induced Steroidogenesis in MA-10 Mouse Leydig Tumor Cells","volume":"22","author":"Venugopal","year":"2021","journal-title":"Int. J. Mol. Sci."},{"issue":"7","key":"2026010813060639700_cit7","doi-asserted-by":"crossref","first-page":"862","DOI":"10.1016\/S0022-2275(20)34782-9","article-title":"Lipid composition and gonadotropin-mediated lipid metabolism of the M5480 murine Leydig cell tumor","volume":"21","author":"Albert","year":"1980","journal-title":"J. Lipid Res."},{"issue":"10043","key":"2026010813060639700_cit8","first-page":"1","article-title":"Oxidative Stress, Testicular Inflammatory Pathways, and Male Reproduction","volume":"22","author":"Dutta","year":"2021","journal-title":"Int. J. Mol. Sci."},{"key":"2026010813060639700_cit9","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1111\/j.1365-2605.1982.tb00312.x","article-title":"Effects of drugs on Leydig cell function","volume":"5","author":"Vermeulen","year":"1982","journal-title":"Int. J. Androl."},{"key":"2026010813060639700_cit10","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1093\/biolre\/ioz174","article-title":"Effects of pharmacologically induced Leydig cell testosterone production on intratesticular testosterone and spermatogenesis","volume":"102","author":"Chung","year":"2020","journal-title":"Biol. 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Pharmacother."},{"key":"2026010813060639700_cit14","first-page":"563","article-title":"Carbamazepine damage to rat spermatogenesis in different sexual developmental phases","author":"De Oliva","year":"2008","journal-title":"Int. J. Androl."},{"key":"2026010813060639700_cit15","doi-asserted-by":"crossref","first-page":"105397","DOI":"10.1016\/j.tiv.2022.105397","article-title":"A comparative study of the effects of 3 testicular toxicants in cultures of seminiferous tubules of rats or of domestic cats (veterinary waste): an alternative method for reprotoxicology","volume":"83","author":"Blondet","year":"2022","journal-title":"Toxicol. In Vitro"},{"key":"2026010813060639700_cit16","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.exger.2015.08.014","article-title":"Steroidogenic Fate of the Leydig Cells that Repopulate the Testes of Young and Aged Brown Norway Rats after Elimination of the Preexisting Leydig Cells","volume":"72","author":"Chen","year":"2015","journal-title":"Exp. Gerontol."},{"key":"2026010813060639700_cit17","first-page":"704","article-title":"Carbamazepine increases atherogenic lipoproteins: mechanism of action in male adults","volume":"282","author":"Bramswig","year":"2001","journal-title":"Am. J. Physiol.: Heart Circ. Physiol."},{"key":"2026010813060639700_cit18","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/S0960-0760(96)00166-5","article-title":"Direct inhibitions of the activities of steroidogenic cytochrome P-450 mono-oxygenase systems by anticonvulsants","volume":"60","author":"Ohnishi","year":"1997","journal-title":"J. Steroid Biochem. Mol. 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Anaesth."},{"issue":"7","key":"2026010813060639700_cit20","doi-asserted-by":"crossref","first-page":"764","DOI":"10.1111\/j.0013-9580.2004.60703.x","article-title":"Differential Effects of Antiepileptic Drugs on Sexual Function and Reproductive Hormones in Men with Epilepsy: Interim Analysis of a Comparison between Lamotrigine and Enzyme-inducing Antiepileptic Drugs","volume":"45","author":"Herzog","year":"2004","journal-title":"Epilepsia"},{"key":"2026010813060639700_cit21","doi-asserted-by":"crossref","first-page":"562","DOI":"10.1177\/096032719501400703","article-title":"A review of drug-induced Leydig cell some comparisons with man","volume":"14","author":"Prentice","year":"1995","journal-title":"Hum. Exp. Toxicol."},{"key":"2026010813060639700_cit22","first-page":"1","article-title":"Replacing fishmeal with salmon hydrolysate reduces the expression of intestinal in fl ammatory markers and modulates the gut microbiota in Atlantic salmon (Salmo salar)","author":"Alvarez-gonza","year":"2024","journal-title":"Front. Biosci.-Landmark"},{"key":"2026010813060639700_cit23","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/0303-7207(96)03802-6","article-title":"The mouse inhibin \u03b1-subunit promoter directs SV40 T-antigen to Leydig cells in transgenic mice","author":"Kananen","year":"1996","journal-title":"Mol. Cell. Endocrinol."},{"key":"2026010813060639700_cit24","doi-asserted-by":"crossref","first-page":"731","DOI":"10.3109\/00365517809104880","article-title":"Effect of carbamazepine, phenytoin and phenobarbitone on serum levels of thyroid hormones and thyrotropin in humans","volume":"38","author":"Rootwelt","year":"1978","journal-title":"Scand. J. Clin. Lab. 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Cell Biol."},{"issue":"1","key":"2026010813060639700_cit49","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1111\/j.1442-2042.2004.00982.x","article-title":"Asthenozoospermia: possible association with long-term exposure to an anti-epileptic drug of carbamazepine","volume":"12","author":"Hayashi","year":"2005","journal-title":"Int. J. 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