ArticleCell death & disease2020
Oxidized-LDL inhibits testosterone biosynthesis by affecting mitochondrial function and the p38 MAPK/COX-2 signaling pathway in Leydig cells.
Article in Cell death & disease, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 61 citations in OpenAlex.
- Lycopene Alleviates T-2 Toxin-Induced Testosterone Synthesis Disorder by Inhibiting ROS/p38/TORC2/CREB Axis.Antioxidants (Basel, Switzerland) · 2026Article
- Dietary patterns and testosterone balance: a review of clinical data and perspectives.Journal of advanced research · 2026Review
- Puerarin ameliorates obesity-induced spermatogenic dysfunction by targeting GRP78/StAR to increase testosterone synthesis.Journal of translational medicine · 2026Article
- miRNA Sequencing and Differential Analysis of Testis in 1-Year-Old and 2-Year-Old Kazakh Horses.Biology · 2026Article
- The EV-mitochondrial outsourcing network as a therapeutic target for age-related testosterone deficiency: from network collapse to clinical intervention.Frontiers in endocrinology · 2026Review
- Spermidine/spermine N1-acetyltransferase1mediates zearalenone-induced toxicity in bovine Leydig cells.Frontiers in cell and developmental biology · 2026Article
- Mechanisms of dyslipidemia-induced erectile dysfunction: a narrative review.Frontiers in endocrinology · 2026Review
- Mitochondrial DNA Deletions and Plasma GDF-15 Protein Levels Are Linked to Hormonal Dysregulation and Multi-Organ Involvement in Female Reproductive Endocrine Disorders.Life (Basel, Switzerland) · 2025Article
- Mechanisms of Leydig Cell Aging and Obesity-Related Hypogonadism in Men: A Review.Medical science monitor : international medical journal of experimental and clinical research · 2025Review
- Melatonin receptor 1a alleviates sleep fragmentation-aggravated testicular injury in T2DM by suppression of TAB1/TAK1 complex through FGFR1.Acta pharmaceutica Sinica. B · 2025Article
- Sex-Specific Impact of 17β-Estradiol and Testosterone Levels on Inflammation and Injury in Acute Myocardial Infarction-Preliminary Results.Biomedicines · 2025Article
- Synergistic Effect of Banaba Leaf Extract and Policosanol (RaydelPharmaceuticals (Basel, Switzerland) · 2025Article
- A novel homozygous frameshift mutation in MCM8 causes primary gonadal dysgenesis in both genders.Journal of assisted reproduction and genetics · 2025Article
- Exploring the Mechanisms of Testicular Aging: Advances in Biomarker Research.Aging and disease · 2025Review
- Article
- Interlinkage between inflammation, oxidative stress, and endoplasmic reticulum stress in bisphenols-induced testicular steroidogenesis disturbance: A mini review.International journal of reproductive biomedicine · 2025Review
- Endothelial Dysfunction with Aging: Does Sex Matter?International journal of molecular sciences · 2024Article
- Twenty-Week Dietary Supplementation with Beeswax Alcohol (BWA; RaydelPharmaceuticals (Basel, Switzerland) · 2024Article
- CXCL16-dependent scavenging of oxidized lipids by islet macrophages promotes differentiation of pathogenic CD8Immunity · 2024Article
- The therapeutic effect and metabolic mechanism analysis of Guilingji on idiopathic oligo-asthenoteratozoospermia.Journal of traditional and complementary medicine · 2024Article
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Abnormal lipid/lipoprotein metabolism induced by obesity may affect spermatogenesis by inhibiting testosterone synthesis in Leydig cells. It is crucial to determine which components of lipoproteins inhibit testosterone synthesis. Circulating oxidized low-density lipoprotein (oxLDL), the oxidized form of LDL, has been reported to be an independent risk factor for decreased serum testosterone levels. However, whether oxLDL has a damaging effect on Leydig cell function and the detailed mechanisms have been rarely studied. This study first showed the specific localization of oxLDL and mitochondrial structural damage in testicular Leydig cells of high-fat diet-fed mice in vivo. We also found that oxLDL reduced the mitochondrial membrane potential (MMP) by disrupting electron transport chain and inhibited testosterone synthesis-related proteins and enzymes (StAR, P450scc, and 3β‑HSD), which ultimately led to mitochondrial dysfunction and decreased testosterone synthesis in Leydig cells. Further experiments demonstrated that oxLDL promoted lipid uptake and mitochondrial dysfunction by inducing CD36 transcription. Meanwhile, oxLDL facilitated COX2 expression through the p38 MAPK signaling pathway in Leydig cells. Blockade of COX-2 attenuated the oxLDL-induced decrease in StAR and P450scc. Our clinical results clarified that the increased serum oxLDL level was associated with a decline in circulating testosterone levels. Our findings amplify the damaging effects of oxLDL and provide the first evidence that oxLDL is a novel metabolic biomarker of male-acquired hypogonadism caused by abnormal lipid metabolism.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.