ArticleJCI insight2024
Paternal hypercholesterolemia elicits sex-specific exacerbation of atherosclerosis in offspring.
Article in JCI insight, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed.
- Elevated zygotic let-7f-5p alters developmental trajectories and sex-specific somatic growth.iScience · 2026Article
- Paternal sleep deprivation and cardiac dysfunction in offspring: A perspective of myocardial hypertrophy.Experimental physiology · 2026Article
- Tfcp2l1 participates in paternal vitamin D deficiency-induced fetal lung maldevelopment in mice.Genes & nutrition · 2026Article
- Paternal Microplastic Exposure Alters Sperm Small Noncoding RNAs and Affects Offspring Metabolic Health in Mice.Journal of the Endocrine Society · 2026Article
- A cholesterol-responsive hepatic tRNA-derived small RNA regulates cholesterol homeostasis and atherosclerosis development.Nature communications · 2025Article
- Microplastic exposure elicits sex-specific atherosclerosis development in lean low-density lipoprotein receptor-deficient mice.Environment international · 2025Article
- Parental Characteristics Associated With Children Born With Neural Tube Defects in Puebla, Mexico.Cureus · 2025Article
- FUSION: a family-level integration approach for robust differential analysis of small non-coding RNAs.Bioinformatics (Oxford, England) · 2025Article
- PANDORA-Seq Unveils the Hidden Small Non-Coding RNA Landscape in Hypopharyngeal Carcinoma.International journal of molecular sciences · 2025Article
- 27-hydroxycholesterol and endothelial cell immune memory link maternal hypercholesterolemia with atherosclerosis in the offspring.Nature cardiovascular research · 2025Article
- Impact of Parental Time-Restricted Feeding on Offspring Metabolic Phenotypic Traits.International journal of biological sciences · 2025Article
- Trained immunity in atherosclerosis: plasticity, metabolic-vascular axis, and AI-driven precision remodeling.Frontiers in immunology · 2025Review
- Emerging roles and therapeutic potential of tRNA-Derived small RNAs in reproductive system diseases: a review.Frontiers in cell and developmental biology · 2025Review
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Authors and funding
7 authors.
Funding
Abstract
Emerging studies suggest that various parental exposures affect offspring cardiovascular health, yet the specific mechanisms, particularly the influence of paternal cardiovascular disease (CVD) risk factors on offspring cardiovascular health, remain elusive. The present study explores how paternal hypercholesterolemia affects offspring atherosclerosis development using the LDL receptor-deficient (LDLR-/-) mouse model. We found that paternal high-cholesterol diet feeding led to significantly increased atherosclerosis in F1 female, but not male, LDLR-/- offspring. Transcriptomic analysis highlighted that paternal hypercholesterolemia stimulated proatherogenic genes, including Ccn1 and Ccn2, in the intima of female offspring. Sperm small noncoding RNAs (sncRNAs), particularly transfer RNA-derived (tRNA-derived) small RNAs (tsRNAs) and rRNA-derived small RNAs (rsRNAs), contribute to the intergenerational transmission of paternally acquired metabolic phenotypes. Using a newly developed PANDORA-Seq method, we identified that high-cholesterol feeding elicited changes in sperm tsRNA/rsRNA profiles that were undetectable by traditional RNA-Seq, and these altered sperm sncRNAs were potentially key factors mediating paternal hypercholesterolemia-elicited atherogenesis in offspring. Interestingly, high-cholesterol feeding altered sncRNA biogenesis-related gene expression in the epididymis but not testis of LDLR-/- sires; this may have led to the modified sperm sncRNA landscape. Our results underscore the sex-specific intergenerational effect of paternal hypercholesterolemia on offspring cardiovascular health and contribute to the understanding of chronic disease etiology originating from parental exposures.
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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 Socratic graph.