Purpose: To examine current evidence of the known effects of advanced paternal age on sperm genetic and epigenetic changes and associated birth defects and diseases in offspring.
Methods: Review of published PubMed literature.
Results: Advanced paternal age (> 40 years) is associated with accumulated damage to sperm DNA and mitotic and meiotic quality control mechanisms (mismatch repair) during spermatogenesis. This in turn causes well-delineated abnormalities in sperm chromosomes, both numerical and structural, and increased sperm DNA fragmentation (3%/year of age) and single gene mutations (relative risk, RR 10). An increase in related abnormalities in offspring has also been described, including miscarriage (RR 2) and fetal loss (RR 2). There is also a significant increase in rare, single gene disorders (RR 1.3 to 12) and congenital anomalies (RR 1.2) in offspring. Current research also suggests that autism, schizophrenia, and other forms of "psychiatric morbidity" are more likely in offspring (RR 1.5 to 5.7) with advanced paternal age. Genetic defects related to faulty sperm quality control leading to single gene mutations and epigenetic alterations in several genetic pathways have been implicated as root causes.
Conclusions: Advanced paternal age is associated with increased genetic and epigenetic risk to offspring. However, the precise age at which risk develops and the magnitude of the risk are poorly understood or may have gradual effects. Currently, there are no clinical screenings or diagnostic panels that target disorders associated with advanced paternal age. Concerned couples and care providers should pursue or recommend genetic counseling and prenatal testing regarding specific disorders.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6030011 | PMC |
http://dx.doi.org/10.1007/s10815-018-1148-y | DOI Listing |
Int J Mol Sci
January 2025
Molecular Genetics Thalassaemia Department, The Cyprus Institute of Neurology & Genetics, Nicosia 2371, Cyprus.
Non-invasive prenatal testing (NIPT) has been widely adopted for the screening of chromosomal abnormalities; however, its adoption for monogenic disorders, such as β-thalassaemia, has proven challenging. Haemoglobinopathies are the most common monogenic disorders globally, with β-thalassaemia being particularly prevalent in Cyprus. This study introduces a non-invasive prenatal haplotyping (NIPH) assay for β-thalassaemia, utilizing cell-free DNA (cfDNA) from maternal plasma.
View Article and Find Full Text PDFSci China Life Sci
January 2025
Institute of Rare Diseases, West China Hospital of Sichuan University, Sichuan University, Chengdu, 610000, China.
Human mitochondrial DNA (mtDNA) harbors essential mutations linked to aging, neurodegenerative diseases, and complex muscle disorders. Due to its uniparental and haploid inheritance, mtDNA captures matrilineal evolutionary trajectories, playing a crucial role in population and medical genetics. However, critical questions about the genomic diversity patterns, inheritance models, and evolutionary and medical functions of mtDNA remain unresolved or underexplored, particularly in the transition from traditional genotyping to large-scale genomic analyses.
View Article and Find Full Text PDFBMC Biol
January 2025
Institute of Rare Diseases, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, 610000, Sichuan, China.
Background: The advancements in second-/third-generation sequencing technologies, alongside computational innovations, have significantly enhanced our understanding of the genomic structure of Y-chromosomes and their unique phylogenetic characteristics. These researches, despite the challenges posed by the lack of population-scale genomic databases, have the potential to revolutionize our approach to high-resolution, population-specific Y-chromosome panels and databases for anthropological and forensic applications.
Objectives: This study aimed to develop the highest-resolution Y-targeted sequencing panel, utilizing time-stamped, core phylogenetic informative mutations identified from high-coverage sequences in the YanHuang cohort.
Compr Psychiatry
January 2025
School of Clinical Medicine, University of New South Wales, Sydney, NSW, Australia; Academic Unit of Child Psychiatry, Liverpool Hospital, Liverpool, NSW, Australia; Ingham Institute of Applied Medical Research and Liverpool Hospital, Sydney, NSW, Australia. Electronic address:
While previous research has examined perinatal factors in the context of Autism Spectrum Disorder (ASD), studies focusing on sociocultural factors is limited. We conducted a cross-sectional analysis utilizing data from the Australian Autism Biobank (AAB), which encompasses autistic children aged 2-17, their siblings, parents, and unrelated controls. Employing multivariable regression analyses, we aimed to identify factors associated with ASD across various domains, spanning health and lifestyle, perinatal, and postnatal contexts.
View Article and Find Full Text PDFCell Biosci
January 2025
Center for Reproduction and Genetics, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230001, China.
Over the past two decades, the study of sperm-borne small non-coding RNAs (sncRNAs) has garnered substantial growth. Once considered mere byproducts during germ cell maturation, these sncRNAs have now been recognized as crucial carriers of epigenetic information, playing a significant role in transmitting acquired traits from paternal to offspring, particularly under environmental influences. A growing body of evidence highlights the pivotal role of these sncRNAs in facilitating epigenetic inheritance across generations.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!