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      Relationship between male aging and semen quality: a retrospective study on over 2500 men

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          Abstract

          Purpose

          We aimed to evaluate whether and to what extent an association exists between male aging and worsening of semen parameters and to determine whether a threshold age can be identified above which the decline in semen quality becomes statistically significant.

          Methods

          2612 men (age: 16–56 years) attending an andrology outpatient clinic for semen analysis and clinical evaluation were studied. Semen analyses were performed according to the ongoing WHO-recommended procedures. Total motile count (TMC) and total progressive motile count (TPMC) were calculated by multiplying total sperm number by total motility and progressive motility, respectively.

          Results

          Significant negative correlations were found between age and total motility ( r = − 0.131, p < 0.0001), progressive motility ( r = − 0.112, p < 0.0001), TPMC ( r = − 0.042, p = 0.037), and normal sperm morphology ( r = − 0.053, p = 0.007). All these associations persisted in multivariate regression models adjusted for abstinence time, smoking, history of male accessory gland infections, varicocele and the year in which semen analysis was performed. When comparisons were performed among quartiles of increasing age, the fourth quartile, corresponding to the age group > 40 years, was associated with a significant decrease in total and progressive motility. An earlier decline in the TPMC and percentage of normal forms was also observed.

          Conclusion

          Advancing male age exhibits an independent association with a decrease in the percentage of motile and morphologically normal spermatozoa, with greater evidence from the age of > 40 years. Further studies are warranted to elucidate the mechanisms and clinical reflections of these associations.

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          Most cited references40

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          Rate of de novo mutations, father’s age, and disease risk

          Mutations generate sequence diversity and provide a substrate for selection. The rate of de novo mutations is therefore of major importance to evolution. We conducted a study of genomewide mutation rate by sequencing the entire genomes of 78 Icelandic parent-offspring trios at high coverage. Here we show that in our samples, with an average father’s age of 29.7, the average de novo mutation rate is 1.20×10−8 per nucleotide per generation. Most strikingly, the diversity in mutation rate of single-nucleotide polymorphism (SNP) is dominated by the age of the father at conception of the child. The effect is an increase of about 2 mutations per year. After accounting for random Poisson variation, father’s age is estimated to explain nearly all of the remaining variation in the de novo mutation counts. These observations shed light on the importance of the father’s age on the risk of diseases such as schizophrenia and autism.
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            The origins, patterns and implications of human spontaneous mutation.

            J F Crow (2000)
            The germline mutation rate in human males, especially older males, is generally much higher than in females, mainly because in males there are many more germ-cell divisions. However, there are some exceptions and many variations. Base substitutions, insertion-deletions, repeat expansions and chromosomal changes each follow different rules. Evidence from evolutionary sequence data indicates that the overall rate of deleterious mutation may be high enough to have a large effect on human well-being. But there are ways in which the impact of deleterious mutations can be mitigated.
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              Differential DNA methylation with age displays both common and dynamic features across human tissues that are influenced by CpG landscape

              Background DNA methylation is an epigenetic modification that changes with age in human tissues, although the mechanisms and specificity of this process are still poorly understood. We compared CpG methylation changes with age across 283 human blood, brain, kidney, and skeletal muscle samples using methylation arrays to identify tissue-specific age effects. Results We found age-associated CpGs (ageCGs) that are both tissue-specific and common across tissues. Tissue-specific ageCGs are frequently located outside CpG islands with decreased methylation, and common ageCGs show the opposite trend. AgeCGs are significantly associated with poorly expressed genes, but those with decreasing methylation are linked with higher tissue-specific expression levels compared with increasing methylation. Therefore, tissue-specific gene expression may protect against common age-dependent methylation. Distinguished from other tissues, skeletal muscle ageCGs are more associated with expression, enriched near genes related to myofiber contraction, and closer to muscle-specific CTCF binding sites. Kidney-specific ageCGs are more increasingly methylated compared to other tissues as measured by affiliation with kidney-specific expressed genes. Underlying chromatin features also mark common and tissue-specific age effects reflective of poised and active chromatin states, respectively. In contrast with decreasingly methylated ageCGs, increasingly methylated ageCGs are also generally further from CTCF binding sites and enriched within lamina associated domains. Conclusions Our data identified common and tissue-specific DNA methylation changes with age that are reflective of CpG landscape and suggests both common and unique alterations within human tissues. Our findings also indicate that a simple epigenetic drift model is insufficient to explain all age-related changes in DNA methylation.
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                Author and article information

                Contributors
                arcangelo.barbonetti@univaq.it
                Journal
                Arch Gynecol Obstet
                Arch Gynecol Obstet
                Archives of Gynecology and Obstetrics
                Springer Berlin Heidelberg (Berlin/Heidelberg )
                0932-0067
                1432-0711
                29 March 2024
                29 March 2024
                2024
                : 309
                : 6
                : 2843-2852
                Affiliations
                Andrology Unit, Department of Clinical Medicine, Life, Health and Environmental Sciences, University of L’Aquila, ( https://ror.org/01j9p1r26) Coppito, 67100 L’Aquila, Italy
                Author information
                http://orcid.org/0000-0002-6888-9585
                Article
                7448
                10.1007/s00404-024-07448-8
                11147833
                38551703
                d6c77aa5-aac5-4c8f-a535-a54d1369c0c9
                © The Author(s) 2024

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 16 November 2023
                : 25 February 2024
                Funding
                Funded by: Università degli Studi dell’Aquila
                Categories
                Gynecologic Endocrinology and Reproductive Medicine
                Custom metadata
                © Springer-Verlag GmbH Germany, part of Springer Nature 2024

                Obstetrics & Gynecology
                ageing,infertility,oxidative stress,sperm morphology,sperm motility,spermatozoa

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