Dataset Information

The combined effect of obesity and aging on human sperm DNA methylation signatures: inclusion of BMI in the paternal germ line age prediction model.

ABSTRACT: Male aging and obesity have both been shown to contribute to declines in fertility in men. Recent work in aging has shown consistent epigenetic changes to sperm as a man ages. In fact, our lab has built a tool that utilizes DNA methylation signatures from sperm to effectively predict an individual's age. Herein, we performed this preliminary cohort study to determine if increased BMI accelerates the epigenetic aging in sperm. A total of 96 participants were divided into four age groups (22-24, 30, 40-41, and?>?48 years of age) and additionally parsed into two BMI sub-categories (normal and high/obese). We found no statistically significant epigenetic age acceleration. However, it is important to note that within each age category, high BMI individuals were predicted to be older on average than their actual age (~?1.4 years), which was not observed in the normal BMI group. To further investigate this, we re-trained a model using only the present data with and without BMI as a feature. We found a modest but non-significant improvement in prediction with BMI [r2?=?0.8814, mean absolute error (MAE)?=?3.2913] compared to prediction without BMI (r2?=?0.8739, MAE?=?3.3567). Future studies with higher numbers of age-matched individuals are needed to definitively understand the impact of BMI on epigenetic aging in sperm.

SUBMITTER: Salas-Huetos A

PROVIDER: S-EPMC7506015 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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The combined effect of obesity and aging on human sperm DNA methylation signatures: inclusion of BMI in the paternal germ line age prediction model.

Salas-Huetos Albert A James Emma R ER Broberg Dallin S DS Aston Kenneth I KI Carrell Douglas T DT Jenkins Timothy G TG

Scientific reports 20200921 1

Male aging and obesity have both been shown to contribute to declines in fertility in men. Recent work in aging has shown consistent epigenetic changes to sperm as a man ages. In fact, our lab has built a tool that utilizes DNA methylation signatures from sperm to effectively predict an individual's age. Herein, we performed this preliminary cohort study to determine if increased BMI accelerates the epigenetic aging in sperm. A total of 96 participants were divided into four age groups (22-24, 3 ...[more]

PMID: 32958862

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Project description:BACKGROUND:Natural and artificial selection leads to changes in certain regions of the genome resulting in selection signatures that can reveal genes associated with the selected traits. Selection signatures may be identified using different methodologies, of which some are based on detecting contiguous sequences of homozygous identical-by-descent haplotypes, called runs of homozygosity (ROH), or estimating fixation index (FST) of genomic windows that indicates genetic differentiation. This study aimed to identify selection signatures in a paternal broiler TT line at generations 7th and 16th of selection and to investigate the genes annotated in these regions as well as the biological pathways involved. For such purpose, ROH and FST-based analysis were performed using whole genome sequence of twenty-eight chickens from two different generations. RESULTS:ROH analysis identified homozygous regions of short and moderate size. Analysis of ROH patterns revealed regions commonly shared among animals and changes in ROH abundance and size between the two generations. Results also suggest that whole genome sequencing (WGS) outperforms SNPchip data avoiding overestimation of ROH size and underestimation of ROH number; however, sequencing costs can limited the number of animals analyzed. FST-based analysis revealed genetic differentiation in several genomic windows. Annotation of the consensus regions of ROH and FST windows revealed new and previously identified genes associated with traits of economic interest, such as APOB, IGF1, IGFBP2, POMC, PPARG, and ZNF423. Over-representation analysis of the genes resulted in biological terms of skeletal muscle, matrilin proteins, adipose tissue, hyperglycemia, diabetes, Salmonella infections and tyrosine. CONCLUSIONS:Identification of ROH and FST-based analyses revealed selection signatures in TT line and genes that have important role in traits of economic interest. Changes in the genome of the chickens were observed between the 7th and 16th generations showing that ancient and recent selection in TT line may have acted over genomic regions affecting diseases and performance traits.

Project description:The impact of aging on reproductive outcomes has received considerable critical attention; however, there is much less information available on the effects of paternal age compared to the effects of maternal age. In this study, methylation levels of sperm rDNA promoter regions and Long Interspersed Nucleotide Element 1 (LINE-1) were measured using pyrosequencing and fertilization, day 3 good-quality embryo, pregnancies, and implantation results were assessed. We observed significantly increasing levels of DNA methylation in the sperm rDNA promoter regions with age based on stratifying the samples by age alone (P = 0.0001) and performing linear regression analysis (P < 0.0001). Meanwhile, no statistically significant correlations were observed between global LINE-1 methylation with age. No statistically significant correlations were observed between sperm rDNA promoter methylation levels and either the day 3 good-quality embryo rate or clinical pregnancy rate. In contrast, the correlation between sperm rDNA promoter methylation levels and fertilization (2 pronuclei) rate was nearly significant (P = 0.0707), especially the methylation levels of some individual CpG units (CpG_10, P = 0.0176; CpG_11, P = 0.0438; CpG_14, P = 0.0232) and rDNA promoter methylation levels measured using primerS2 (P = 0.0513). No significant correlation was found between sperm rDNA promoter methylation levels and fertilization rates (2 pronuclei, 1 pronuclei, and 1 polypronuclei). Our results demonstrate that sperm are susceptible to age-associated alterations in methylation levels of rDNA promoter regions, suggesting that sperm rDNA promoter methylation levels can be applied to DNA methylation-based age prediction, and that the aberrant methylation of rDNA promoters may be partially responsible for enhanced disease susceptibility of offspring sired by older fathers. Methylation levels of sperm rDNA promoter regions may correlate with polypronuclei rates of IVF programs.

Dataset Information

The combined effect of obesity and aging on human sperm DNA methylation signatures: inclusion of BMI in the paternal germ line age prediction model.

Publications

The combined effect of obesity and aging on human sperm DNA methylation signatures: inclusion of BMI in the paternal germ line age prediction model.

Similar Datasets

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