ArticleJournal of cellular and molecular medicine2019
HC diet inhibited testosterone synthesis by activating endoplasmic reticulum stress in testicular Leydig cells.
Article in Journal of cellular and molecular medicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 1 of them a synthesis that pooled it.
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Who cites it
31 citing papers in PubMed, 1 synthesis or guideline pooled it, 59 citations in OpenAlex.
- Obstructive sleep apnea and serum total testosterone: a system review and meta-analysis.Sleep & breathing = Schlaf & Atmung · 2023Pooled it
- Dietary patterns and testosterone balance: a review of clinical data and perspectives.Journal of advanced research · 2026Review
- Chlorella vulgaris and Lactobacillus casei Combination Therapy Attenuates Testicular Endoplasmic Reticulum Stress and Dysfunction in a C57BL/6 Mouse Model of NAFLD.Probiotics and antimicrobial proteins · 2026Article
- Transcriptomics and metabolomics reveal functional nanoplastics-induced male reproductive damage and resveratrol antagonistic effects.Journal of nanobiotechnology · 2026Article
- High-fat diet leads to male reproductive dysfunction by disrupting lipid-droplet-mediated organelle crosstalk.Cellular & molecular biology letters · 2026Article
- Mechanisms of dyslipidemia-induced erectile dysfunction: a narrative review.Frontiers in endocrinology · 2026Review
- Policosanol ameliorates testicular injury and improves steroidogenesis in diabetic hypercholesterolemic rats.Molecular biology reports · 2025Article
- Lifestyle in flux: urbanization, dietary shifts, and endocrine health in emerging adulthood.Reproductive biology and endocrinology : RB&E · 2025Article
- The downregulation of hormone-sensitive lipase and dysregulation of cholesterol receptors/transporter affect testicular lipid homeostasis and function in HFD-induced oligoasthenospermia mice.Molecular medicine (Cambridge, Mass.) · 2025Article
- Simvastatin-Mediated Molecular Mechanisms Underlying the Growth Inhibition of Testicular Leydig Tumour Cells.Journal of cellular and molecular medicine · 2025Article
- Effect of High-Intensity Interval Training on Mitigating High-Fat Diet-Induced Damage in Rat Testicular Tissue.Preventive nutrition and food science · 2025Article
- Omega-3 polyunsaturated fatty acids ameliorate high-fat-diet-induced structural and functional impairments of testicular tissue via ER stress inhibition.Transgenic research · 2025Article
- SLC7A11 as a therapeutic target to attenuate phthalates-driven testosterone level decline in mice.Journal of advanced research · 2025Article
- Cholesterol and SREBP2 Dynamics During Spermatogenesis Stages in Rabbits: Effects of High-Fat Diet and Protective Role of Extra Virgin Olive Oil.International journal of molecular sciences · 2025Article
- Age-related testosterone decline: mechanisms and intervention strategies.Reproductive biology and endocrinology : RB&E · 2024Review
- Sexual dimorphism in a mouse model of Friedreich's ataxia with severe cardiomyopathy.Communications biology · 2024Article
- The Influence of a High-Cholesterol Diet and Forced Training on Lipid Metabolism and Intestinal Microbiota in Male Wistar Rats.International journal of molecular sciences · 2024Article
- Dietary Patterns and Fertility.Biology · 2024Review
- Kisspeptin-10 Improves Testicular Redox Status but Does Not Alter the Unfolded Protein Response (UPR) That Is Downregulated by Hypothyroidism in a Rat Model.International journal of molecular sciences · 2024Article
- High cholesterol diet-induced testicular dysfunction in rats.Hormones (Athens, Greece) · 2023Article
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Emerging epidemiological studies indicate that hypercholesterolaemia is a risk factor for testosterone deficiency. However, the underlying mechanism is unclear. Testicular Leydig cells are the primary source of testosterone in males. To identify the effect and mechanism of cholesterol overload on Leydig cell function, rats were fed with a HC (HC) diet to induce hypercholesterolaemia. During the 16-week feeding period, serum testosterone levels were reduced in a time-dependent manner in rats fed the HC diet. Accordingly, these steroidogenic enzymes within the Leydig cells, including steroidogenic acute regulatory protein (StAR), cholesterol side-chain cleavage cytochrome P450 (P450scc) and 3β-hydroxysteroid dehydrogenase (3β-HSD), were down-regulated. Notably, the HC-fed rats showed evident endoplasmic reticulum (ER) stress in the testis, including a dilated ER as an evident pathological change in the Leydig cell ultrastructure, up-regulated ER stress biomarker (binding immunoglobulin protein) levels and activation of the activating transcription factor 6 (ATF6)-related unfolded protein response pathway. Further analysis showed that when 4-phenyl butyric acid (4-PBA) was used to block ER stress in HC-fed rats for 8 weeks, the testosterone deficiency was significantly alleviated. Our findings suggested that high dietary cholesterol intake affected serum testosterone levels by down-regulating steroidogenic enzymes and that activated ER stress might serve as the underlying mechanism.
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Registered trials
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.