The necroptosis-mediated imbalance of mitochondrial dynamics is involved in DEHP-induced toxicity to immature testes via the PGAM5–DRP1 interaction

Environmental Pollution, Journal Year: 2024, Volume and Issue: 346, P. 123585 - 123585

Published: Feb. 15, 2024

Language: Английский

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Plin4 exacerbates cadmium-decreased testosterone level via inducing ferroptosis in testicular Leydig cells

Redox Biology, Journal Year: 2024, Volume and Issue: 76, P. 103312 - 103312

Published: Aug. 17, 2024

Strong evidence indicates that environmental stressors are the risk factors for male testosterone deficiency (TD). However, mechanisms of stress-induced TD remain unclear. Based on our all-cause reproductive cohort, we found serum ferrous iron (Fe

Language: Английский

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Melatonin alleviates glyphosate-induced testosterone synthesis inhibition via targeting mitochondrial function in roosters

Environmental Pollution, Journal Year: 2024, Volume and Issue: 348, P. 123828 - 123828

Published: March 22, 2024

Language: Английский

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The Role of Melatonin to Ameliorate Oxidative Stress in Sperm Cells

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(20), P. 15056 - 15056

Published: Oct. 11, 2023

It is widely accepted that oxidative stress (OS) coming from a wide variety of causes has detrimental effects on male fertility. Antioxidants could have significant role in the treatment infertility, and current systematic review melatonin to ameliorate OS clearly shows improvement semen parameters follows supplementation. Although considerable promise, further studies are needed clarify its ability preserve or restore quality under conditions varied species. The present examines actions via receptor subtypes function context across vertebrates.

Language: Английский

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Mitochondrial ROS-associated integrated stress response is involved in arsenic-induced blood-testis barrier disruption and protective effect of melatonin

Environment International, Journal Year: 2025, Volume and Issue: 197, P. 109346 - 109346

Published: Feb. 23, 2025

Arsenic (As) is an environmental metalloid. Previous studies have demonstrated that As exposure resulted in decline of sperm quality. This study aimed to investigate the impact on blood-testis barrier (BTB) a mouse model. Four-week-old male mice were exposed NaAsO2 (1 or 15 mg/L) for 6 weeks. Our results found disrupted BTB and reduced counts adult mice. activated integrated stress response (ISR) downregulated junction protein testes Sertoli cells. Ribosome profiling sequencing (Ribo-seq) Ribosome-nascent chain complex-bound mRNA qPCR (RNC-qPCR) showed translational efficiency N-cadherin ZO-1, two key proteins, was NaAsO2-treated Mechanistically, SIRT3 via proteasomal degradation, thereby resulting mitochondrial dysfunction excess ROS (mtROS) generation Melatonin alleviated NaAsO2-induced mtROS upregulation reducing SOD2 acetylation Moreover, melatonin antagonized ISR, proteins downregulation function impairment Accordingly, attenuated NaAsO2-evoked disruption count reduction These suggest dysfunction-associated inhibition involved As-mediated quality decline.

Language: Английский

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DAPK3 is Essential for DBP‐Induced Autophagy of Mouse Leydig Cells

Advanced Science, Journal Year: 2025, Volume and Issue: unknown

Published: March 6, 2025

Dibutyl phthalate (DBP) has been widely used in the manufacture of various daily and industrial products. As one most important endocrine disruptors, DBP male reproductive toxicity can lead to testicular dysfunction. In view fact that Leydig cells are functional structural units testis, their damage will affect function. However, underlying mechanism DBP-caused mouse remains elusive. study, it is confirmed promote expression death-associated protein kinase 3 (DAPK3), thereby inducing autophagy by using vivo vitro experiments. Also, bioinformatics analysis molecular biology experimental techniques utilized further demonstrate DBP-induced upregulation DAPK3 results from both activated transcription specific 2 (Sp2) decreased ubiquitination degradation parkin RBR E3 ubiquitin-protein ligase (PRKN). Interestingly, melatonin inhibit Sp2/DAPK3 PRKN/DAPK3 signaling pathways inhibiting oxidative stress, alleviating cells. Overall, study unravels a novel regulatory identifies as potential therapeutic target for system.

Language: Английский

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Melatonin Repairs the Lipidome of Human Hepatocytes Exposed to Cd and Free Fatty Acid‐Induced Lipotoxicity

Journal of Pineal Research, Journal Year: 2025, Volume and Issue: 77(3)

Published: April 1, 2025

ABSTRACT Hepatocyte lipotoxicity is central to the aetiology of nonalcoholic fatty liver disease (NAFLD), a leading cause failure and transplantation worldwide. Long‐lasting toxic pollutants have increasingly been considered as environmental risk factors NAFLD. These include cadmium (Cd), metal that synergizes with other cellular toxicants metabolic stimuli induce fat build‐up lipotoxicity. Recent studies demonstrated melatonin (MLT) holds great potential repairing agent in this form hepatocyte In study, molecular hints MLT effect were investigated by lipidomics analysis undifferentiated HepaRG cells, human pre‐hepatocyte cell line, exposed Cd toxicity either alone or combined prototypical free acids (FFA), namely saturated species palmitic acid monounsaturated oleic (OA PA, respectively), simulate conditions disease. exposure synergized FFAs steatosis, PA produced higher levels compared OA increased H 2 O production apoptotic death. effects associated changes lipidome, which approximate those NAFLD liver, differentially expressed lipids different classes included triacylglycerols (TG), di‐ mono‐acylglycerols, phospholipids (PL), sphingolipids, acylcarnitines FA; characteristic differences observed all these comparing combinations treatments. significantly reduced individual combinatorial treatments on hallmarks, also most alterations including chain length number double bonds acyl residues esterified TG PL classes. findings their bioinformatics interpretation suggest role for earliest elongase desaturase steps FA metabolism MLT; biochemistry validated such identifying specific SCD1 activity. This study shed light cytoprotective mechanism FFA‐induced lipotoxicity, highlighting molecule may hold therapeutic diseases.

Language: Английский

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Protective effects of melatonin against oxidative stress induced by metabolic disorders in the male reproductive system: a systematic review and meta-analysis of rodent models

Frontiers in Endocrinology, Journal Year: 2023, Volume and Issue: 14

Published: July 5, 2023

Background Male infertility is a multifaceted issue that has gained scientific interest due to its increasing rate. Studies have demonstrated oxidative stress involved in male development. Furthermore, metabolic disorders, including obesity, diabetes, hypo- and hyperthyroidism, are risk factors for infertility, believed contribute this association. Melatonin, functioning as an scavenger, may represent promising therapeutic approach the prevention treatment of disorder-associated infertility. Material methods We systematically searched three online databases (PubMed, Scopus, Web Science) studies evaluated effects melatonin therapy on disorders-induce rodents. The favorable outcomes were histopathological parameters testicular tissue, reproductive hormones, markers stress. Then, meta-analyses done each outcome. results reported standardized mean difference (Cohen’s d) 95% confidence interval. Results 24 with 31 included. Rats mice subjects. employed hypothyroidism, hyperlipidemia, food deprivation disorders. To induce these high-fat diet, high‐fructose leptin, streptozotocin, alloxan, carbimazole, levothyroxine used. included histopathologic characteristics (abnormal sperm morphology, apoptotic cells, index, Johnsen’s biopsy score, seminiferous epithelial height, tubular basement membrane thickness, diameter, count, motility), weight-related measurements (absolute epididymis, testis, body weight, weight gain, epididymal adipose tissue relative testis weight), hormonal (androgen receptor expression, serum FSH, LH, testosterone level), (tissue GPx MDA activity, CAT, GSH, SOD activity), exploratory (serum HDL, LDL, total cholesterol, triglyceride, blood glucose level). overall pooled effect sizes statistically significant all some Conclusions Melatonin can reduce damage rodents’ gonadal improve motility, morphology diseases. Future clinical randomized controlled trials needed evaluate safety effectiveness patients

Language: Английский

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Protective effects of exogenous melatonin therapy against oxidative stress to male reproductive tissue caused by anti-cancer chemical and radiation therapy: a systematic review and meta-analysis of animal studies

Frontiers in Endocrinology, Journal Year: 2023, Volume and Issue: 14

Published: Aug. 28, 2023

Background Male testicular dysfunction is a considerable complication of anti-cancer therapies, including chemotherapy and radiotherapy, partly due to the increased oxidative stress caused by these treatments. Melatonin an effective antioxidant agent that protects testicles against physical toxic chemical stressors in animal models. This study aims systematically review melatonin’s protective effects on rodential tissue. Materials Method An extensive search was conducted Web Science, Scopus, PubMed for studies investigating exogenous rodent exposed chemicals radiotherapeutic agents. Using DerSimonian Laird random-effect model, standardized mean differences 95% confidence intervals were estimated from pooled data. The protocol prospectively registered International Prospective Register Systematic Reviews (PROSPERO: CRD42022355293). Results meta-analysis included 38 43 eligible review. Rats mice radiotherapy (ionizing radiations such as gamma- roentgen radiation radioactive iodine) or (methotrexate, paclitaxel, busulfan, cisplatin, doxorubicin, vinblastine, bleomycin, cyclophosphamide, etoposide, Taxol, procarbazine, docetaxel, chlorambucil). According our meta-analysis, all outcomes significantly improved melatonin therapy, sperm quantity quality (count, motility, viability, normal morphology, number spermatogonia, Johnsen’s biopsy score, seminiferous tubular diameter, epithelial height), serum level reproductive hormones (Follicle-Stimulating Hormone testosterone), tissue markers (testicular malondialdehyde, superoxide dismutase, glutathione peroxidase, catalase, glutathione, caspase-3, total capacity), weight-related characteristics (absolute body, epididymis, testis, relative testis body weights). Most SYRCLE domains exhibited high risk bias studies. Also, significant heterogeneity small-study detected. Conclusion In male rodents, therapy related histopathology, hormones, weights, reduced levels tissues rodents. Future meticulous are recommended provide robust scientific backbone human applications. registration https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022355293 , identifier CRD42022355293.

Language: Английский

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Melatonin increased antioxidant capacity to ameliorate growth retardation and intestinal epithelial barrier dysfunction in diquat‐challenged piglets

Journal of the Science of Food and Agriculture, Journal Year: 2023, Volume and Issue: 104(4), P. 2262 - 2271

Published: Nov. 10, 2023

Diquat is a common environmental pollutant, which can cause oxidative stress in humans and animals. exposure causes growth retardation intestinal damage. Therefore, this study was performed to investigate the effects of melatonin on diquat-challenged piglets.

Language: Английский

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