Tatehana, M. | Search bioRxiv

bioRxiv2023

Unveiling the intricacies: Investigating the impact of paternal aging on murine sperm miRNA profiles and their potential link to autism spectrum disorder

Paternal aging has consistently been linked to an increased risk of neurodevelopmental disorders, including autism spectrum disorder (ASD), in offspring. Recent evidence has highlighted the involvement of epigenetic factors. In this study, we aimed to investigate age-related alterations in microRNA (miRNA) profiles of mouse sperm and analyze target genes regulated by differentially expressed miRNAs (DEmiRNAs). Microarray analyses were conducted on sperm samples from mice at different ages: 3 months (3 M), over 12 M, and beyond 20 M. We identified 26 miRNAs with differential expression between the 3 M and 20 M mice, 34 miRNAs between the 12 M and 20 M mice, and 2 miRNAs between the 3 M and 12 M mice. The target genes regulated by these miRNAs were significantly associated with apoptosis/ferroptosis pathways and the nervous system. We revealed alterations in sperm miRNA profiles due to aging and suggest that the target genes regulated by these DEmiRNAs are associated with apoptosis and the nervous system, implying a potential link between paternal aging and an increased risk of neurodevelopmental disorders such as ASD. The observed age-related changes in sperm miRNA profiles have the potential to impact sperm quality and subsequently affect offspring development.

developmental biology↗

bioRxiv2019

Detailed profiles of histone modification in male germ line cells of the young and aged mice

Human epidemiological studies have shown paternal aging as one of the risks for neurodevelopmental disorders such as autism in offspring. A recent study has suggested that factors other than de novo mutations due to aging can influence biology of offspring. Here we are focusing on epigenetic alterations in sperm that can influence offspring developmental programs. In this study, we qualitatively and semi-quantitatively evaluated histone modification patterns in male germ line cells throughout spermatogenesis based on immunostaining of testes taken from young (3 months) and aged (12 months) old mice. Although localization patterns were not obviously changed between young and aged testes, some histone modification showed differences in their intensity. Among histone modifications that repress gene expression, H3K9me3 was decreased in the male germ line cells in the aged testis, while H3K27me2/3 was increased. The intensity of H3K27ac, an active mark, was relatively low in the aged testis. Interestingly, H3K27ac was detected in putative sex chromosomes of round spermatids, while other chromosomes were occupied by a repressive mark H3K27me3. Among other histone modifications that activate gene expression, H3K4me2 was drastically decreased in the male germ line cells in the aged testis. H3K79me3 was contrastingly increased and accumulated on the sex chromosomes at M-phase spermatocytes. Therefore, aging induced alterations in the amount of histone modifications, of which patterns were different in individual histone modifications. Moreover, histone modification seems to be differentially regulated by aging on the sex chromosomes and on others. These findings would help elucidate epigenetic mechanisms underlying influence of paternal aging on offsprings development.

developmental biology↗