ECE2023 Poster Presentations Diabetes, Obesity, Metabolism and Nutrition (159 abstracts)
High-fat diet promotes 3’mt-tiRNA-Met epididymosome enrichment which correlates to lower spermatozoa mitochondrial translation
Sara C. Pereira 1,2,3,4,5 , Laís Freire-Brito 1,2 , Bárbara Guerra-Carvalho 1,2,3,4,5 , David F. Carrageta 1,2,5 , Raquel Bernardino 1,2 , Luís Crisóstomo 6 , Simona Terzo 7 , Mariana P. Monteiro 1,2 , Pedro F. Oliveira 3 , Mario Allegra 7 & Marco Alves 1,2,5
1School of Medicine and Biomedical Sciences (ICBAS), University of Porto, 4050-313 Porto, Portugal, Endocrine and Metabolic Research, Unit for Multidisciplinary Research in Biomedicine, Porto, Portugal; 2University of Porto, Laboratory for Integrative and Translational Research in Population Health (ITR), Porto, Portugal; 3University of Aveiro, LAQV-REQUIMTE and Department of Chemistry, Aveiro, Portugal; 4Faculty of Medicine, University of Porto, Department of Pathology, Porto, Portugal; 5School of Medicine and Biomedical Sciences (ICBAS), University of Porto, Laboratory of Physiology, Department of Imuno-Physiology and Pharmacology, Porto, Portugal; 6Institute of Biomedicine, University of Turku, Turku, Finland; 7University of Palermo, Department of Pharmaceutical, Toxicological and Biological Chemistry, Palermo, Italy
Metabolic and endocrine dysregulation induced by high-fat diet (HFD) can lead to decreased male fertility potential and have a negative impact on the offspring’s metabolic health. Small non-coding RNAs (sncRNAs) were proposed as being potential mediators of metabolic queues across transgenerational inheritance. During development and epidydimal transit, spermatozoa become enriched with tRNA-derived stress-induced RNAs (tiRNAs). This sncRNAs class appears to be particularly important for sperm quality and embryo development, through processes that are now starting to be unveiled. Herein, we hypothesized that mitochondrial tiRNAs (mt-tiRNAs) are integrated into the spermatozoa through epididymosomes. Further, we propose that HFD can alter the mt-tiRNAs carried by epididymosomes, which can then impact sperm quality. To test our hypothesis, 4-week-old male C57BL mice were fed ad libitum with an HFD or standard diet (control) for 14 weeks. Size characterization showed no significant difference between epididymosomes vesicle size from the two groups, although the HFD group presented a tendency for a greater epididymosome concentration (nearly 2-fold). We also found an increased abundance of 3’mt-tiRNAMet in epididymosomes from the HFD group. Under stressful conditions, tiRNAs expression often becomes upregulated at different somatic cell lines. Additionally, higher tiRNAs expression is usually correlated to decreased translation. To explore spermatozoa mitochondrial translation function, we assessed mitochondrial 12S rRNA abundance. HFD mice presented lower 12S rRNA levels on spermatozoa, as well as higher 3’mt-tiRNAMet levels on epididymosomes when compared to the control group. A positive correlation between spermatozoa 12S rRNA expression levels and normal sperm morphology was also found. Concurrently, higher 12S rRNA expression levels were negatively correlated with spermatozoa tail defects. Our results suggest that mt-tiRNAs have an important role in spermatozoa HFD-induced stress (dys)regulation. Most particularly 3’mt-tiRNAMet, expressed by the epididymis, carried by epididymosomes, and integrated into the spermatozoa, might take part in the molecular mechanisms by which the HFD induces deleterious effects on sperm quality with a potential negative impact on male fertility.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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