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Sperm methylome alterations following yoga-based lifestyle intervention in patients of primary male infertility: A pilot study

ABSTRACT: A majority of the cases of primary male infertility are idiopathic with the underlying molecular mechanisms contributing to the pathophysiology as yet unknown. Effects of the environment can alter the sperm epigenome thereby impacting male reproduc-tive health. Epigenetic mechanisms are crucial to understanding health and disease, and methylome alterations are now known to have far-reaching clinical implications. Here, we report the results from our pilot study, a first of its kind analysis of the ef-fect of the traditional practice of yoga on human sperm quality. We find marked im-provement in sperm characteristics in patients of idiopathic male infertility following asupervised21-dayyogaregimen.Furthermore,next-generationsequencing-basedmethylome analysis reveals alterations in the sperm epigenome of these patients. We find that the practice of yoga is associated with DNA methylation changes at nearly 400 genes, 147 of which were hypermethylated while 229 were hypomethyl-ated. These included promoters of several genes linked to maintenance of fertility and genomic integrity. This novel piece of work draws a direct link between positive lifestyle practices and male reproductive health.

ORGANISM(S): Homo sapiens

PROVIDER: GSE180430 | GEO | 2021/07/23

REPOSITORIES: GEO

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Project description:Environmental toxicants have been shown to induce the epigenetic transgenerational inheritance of adult onset disease, including testis disease and male infertility. The exposure of a gestating female during the period of gonadal sex determination has been shown to promote sperm epimutations, differential DNA methylation regions (DMR), that transmit transgenerational disease to subsequent generations. The current study was designed to determine the impact of an altered sperm epigenome on the subsequent development of an adult somatic cell (Sertoli cell) that influences the onset of a specific disease (male infertility). A gestating female rat (F0 generation) was exposed to the agriculture fungicide vinclozolin during gonadal sex determination and then the subsequent F3 generation progeny used for the isolation of Sertoli cells and assessment of testis disease. As previously observed, a spermatogenic cell apoptosis was observed. The Sertoli cells that provide the physical and nutritional support for the spermatogenic cells were isolated and alterations in gene expression examined. Over 400 genes were differentially expressed in the F3 generation control versus vinclozolin lineage Sertoli cells. A number of specific signaling pathways and cellular processes were identified to be transgenerationally altered. One of the key metabolic processes affected was pyruvate/lactate production that is directly linked to spermatogenic cell viability. The Sertoli cell epigenome was also altered with over 100 promoter differential DNA methylation regions (DMR) modified in the vinclozolin F3 generation Sertoli cell. The genomic features and overlap with the sperm DMR were investigated. Observations demonstrate that the transgenerational sperm epigenetic alterations subsequently alters the development of a specific somatic cell (Sertoli cell) epigenome and transcriptome that then has a role in the adult onset disease (male infertility). The environmentally induced epigenetic transgenerational inheritance of testis disease appears to be a component of the molecular etiology of male infertility. Environmental toxicants have been shown to induce the epigenetic transgenerational inheritance of adult onset male infertility. The exposure of a gestating female during the period of gonadal sex determination has been shown to promote sperm epimutations, differential DNA methylation regions (DMR), that transmit transgenerational disease to subsequent generations. The current study was designed to determine the impact of an altered sperm epigenome on the subsequent development of an adult somatic cell (Sertoli cell) that influences the onset of a specific disease (male infertility). A gestating female rat (F0 generation) was exposed to the agriculture fungicide vinclozolin during gonadal sex determination and then the subsequent F3 generation progeny used for the isolation of Sertoli cells and assessment of testis disease. The Sertoli cells provide the physical and nutritional support for the spermatogenic cells in the testis. The F3 generation Sertoli cells have an altered transcriptome and epigenome associated with adult onset testis disease. The environmentally induced epigenetic transgenerational inheritance of Sertoli cell abnormalities appears to be a component of the molecular etiology of male infertility. RNA samples from Sertoli cell of 3 F3-control lineage groups are compared to Sertoli cell of 3 F3-vinclozolin lineage groups

Project description:Infertility is a widespread problem, affecting around 15% of couples worldwide, and is defined as the inability to achieve pregnancy within one year despite unprotected intercourse 1. Infertility can be caused by either male or female reproductive issues. Various medical conditions including malignancies, infections, urogenital conditions, or genetic causes can contribute to male infertility. However, 30-40% of men in their reproductive age are affected by idiopathic infertility, according to the guidelines of European Association of Urology (EAU) 1. Towards a better understanding of male infertility, it is mandatory to achieve a comprehensive understanding of involved genes, their RNA transcripts, and regulatory factors, including miRNAs, which influence the expression level of proteins. Therefore, such proteins need to be identified to investigate their role in spermatogenesis and male infertility. Although there are numerous studies on RNAs, including miRNAs related to male infertility 2-9, there are few studies aiming to cover the whole proteome of human sperm 10. The sperm transcriptome comprises a total of 60,505 transcripts including 11,688 differentially expressed transcripts in infertile and fertile men, as reported by Joshi et al. (2022)11. The entire sperm proteome encompasses 6871 proteins, as summarized by Castillo et al. (2018)10. Nevertheless, there is still a lack of high-throughput studies aiming to identify dysregulated proteins in sperm from subfertile men. Only few studies focused on comparisons of the sperm proteome in men with asthenozoospermia and there is virtually no proteomic studies of oligoasthenozoospermic men 12. Some identified proteins in sperm have functions in maintaining sperm motility and enabling fertilization and are involved in structural composition and/or energy metabolism 12-14 and others are not yet functionally characterized. In this study, we employed Mass spectrometry (MS) technology that is still rarely used in the field of human reproductive research to investigate the proteomic landscape of human sperm and their differential expression patterns in men with subfertility.

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Sperm methylome alterations following yoga-based lifestyle intervention in patients of primary male infertility: A pilot study

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