Genome medicine in male infertility: From karyotyping to single-cell analysis

Abstract

Male infertility is a multifactorial pathological condition that affects half of infertile couples. The majority of cases are categorized as idiopathic, especially in cases of nonobstructive azoospermia (NOA). An increasing number of genetic abnormalities have been shown to cause spermatogenic impairment with the development of microarray technologies and next-generation sequencing (NGS), moving beyond classical karyotype and polymerase chain reaction analyses of targeted genes. However, the majority of gene mutations, such as Klinefelter syndrome, azoospermia factor microdeletion, or congenital bilateral absence of the vas deferens, fail to function in a one gene-one phenotype manner. Single-cell transcriptome analysis performed using human testicular samples has begun to be published, which has brought about a more comprehensive understanding of testicular pathology. NGS also enables omics approaches, which provide more powerful tools to interrogate the genome, epigenome, transcriptome, and proteome. Simultaneously, the involvement of environmental factors and comorbidities, which may potentially regulate epigenetic factors, has been shown, resulting in a more complex understanding of the pathophysiology of spermatic disorders, especially NOA. The combination of phenotypic data and large amounts of bioinformatical data obtained by NGS may provide a more comprehensive understanding of the pathophysiology of male infertility, which will contribute not only to a diagnosis but also to the proper selection of infertility treatment and the development of new treatment modalities for male infertility.

Keywords: genome medicine; male infertility; microarray; single-cell analysis; transcriptome analysis.