ABSTRACT
Spermatozoa harbour a complex and environment-sensitive pool of small non-coding RNAs (sncRNAs)1, which influences offspring development and adult phenotypes1-7. Whether spermatozoa in the epididymis are directly susceptible to environmental cues is not fully understood8. Here we used two distinct paradigms of preconception acute high-fat diet to dissect epididymal versus testicular contributions to the sperm sncRNA pool and offspring health. We show that epididymal spermatozoa, but not developing germ cells, are sensitive to the environment and identify mitochondrial tRNAs (mt-tRNAs) and their fragments (mt-tsRNAs) as sperm-borne factors. In humans, mt-tsRNAs in spermatozoa correlate with body mass index, and paternal overweight at conception doubles offspring obesity risk and compromises metabolic health. Sperm sncRNA sequencing of mice mutant for genes involved in mitochondrial function, and metabolic phenotyping of their wild-type offspring, suggest that the upregulation of mt-tsRNAs is downstream of mitochondrial dysfunction. Single-embryo transcriptomics of genetically hybrid two-cell embryos demonstrated sperm-to-oocyte transfer of mt-tRNAs at fertilization and suggested their involvement in the control of early-embryo transcription. Our study supports the importance of paternal health at conception for offspring metabolism, shows that mt-tRNAs are diet-induced and sperm-borne and demonstrates, in a physiological setting, father-to-offspring transfer of sperm mitochondrial RNAs at fertilization.
Subject(s)
Diet, High-Fat , Epigenesis, Genetic , Mitochondria , RNA, Mitochondrial , Spermatozoa , Animals , Female , Humans , Male , Mice , Body Mass Index , Diet, High-Fat/adverse effects , Embryo, Mammalian/cytology , Embryo, Mammalian/embryology , Embryo, Mammalian/metabolism , Epididymis/cytology , Epigenesis, Genetic/genetics , Fertilization/genetics , Gene Expression Profiling , Gene Expression Regulation, Developmental , Mice, Inbred C57BL , Mitochondria/genetics , Mitochondria/metabolism , Mitochondria/pathology , Obesity/genetics , Obesity/metabolism , Obesity/etiology , Oocytes/metabolism , Overweight/genetics , Overweight/metabolism , Paternal Inheritance/genetics , RNA, Mitochondrial/genetics , RNA, Mitochondrial/metabolism , RNA, Small Untranslated/genetics , RNA, Small Untranslated/metabolism , RNA, Transfer/genetics , RNA, Transfer/metabolism , Spermatozoa/metabolism , Testis/cytology , Transcription, GeneticABSTRACT
BACKGROUND: The Brief Symptom Inventory-18 (BSI-18) is a self-report questionnaire with three subscales, somatisation, anxiety, and depression, based on longer measures of distress. The present study proposes a shorter, nine-item version (BSI-9) of the BSI-18 as a brief screening tool for distress. METHODS: Confirmatory factor analyses and reliability and validity analyses were carried out using a representative sample of the German general population. Confirmatory factor analysis demonstrates a good model fit for the three-dimensional BSI-9. RESULTS: The total scale was found to have strong internal consistency (αCronbach = 0.87 for the global severity index). The internal consistency coefficients of the three-item subscales reflect the brevity of these scales (somatisation αCronbach = 0.72, depression α Cronbach = 0.79, anxiety αCronbach = 0.68). The subscales were found to be significantly related with subscales of the Patient Health Questionnaire-4 and Hopkins Symptom Checklist-25. LIMITATIONS: The present study used a limited number of distress measures, and a more recent dataset would be useful to provide a more current picture of the general population's distress levels. CONCLUSIONS: The BSI-9 provides a short, valid, and reliable screener for distress in the general population. Future work should examine its utility in clinical settings and different cultural contexts.
Subject(s)
Anxiety , Depression , Psychometrics , Adolescent , Adult , Aged , Female , Humans , Male , Middle Aged , Young Adult , Anxiety/diagnosis , Anxiety/psychology , Depression/diagnosis , Factor Analysis, Statistical , Germany , Psychiatric Status Rating Scales/standards , Psychological Distress , Psychometrics/instrumentation , Reproducibility of Results , Self Report , Somatoform Disorders/diagnosis , Somatoform Disorders/psychology , Surveys and Questionnaires/standards , Aged, 80 and overABSTRACT
RESEARCH AIM: Nicotinamide phosphoribosyltransferase (Nampt) is an adipocytokine that is elevated in obesity, type 2 diabetes and increased levels are associated with inflammatory processes. Nampt serum concentrations have been suggested to follow a diurnal rhythm peaking in the afternoon in lean males. However, no data exists regarding the effects of gender and body weight. MATERIAL AND METHODS: We measured Nampt serum levels over 24 h in a cohort of healthy individuals living with either normal weight or obesity. Furthermore, effects of meals, oral glucose tolerance test and physical exercise on Nampt concentrations were evaluated. Correlation analyses to other hormonal- and lab parameters and anthropometric measurements were performed. RESULTS: Nampt showed a diurnal rhythm with increased levels at daytime and a peak in the early afternoon. This diurnal rhythm was significant for all groups but obese males. The Nampt amplitude, measured both relatively and absolutely, was significantly higher in females than in males. Meals did not influence Nampt serum levels, whereas physical exercise and an OGTT did significantly influence Nampt serum levels. CONCLUSION: In conclusion, we found gender specific differences in Nampt amplitude and coefficient variation with both being higher in females. The circadian rhythm of Nampt was independent of gender in healthy lean individuals, whereas it was disturbed in men with obesity.