Emerging molecular methods for male infertility investigation

Abstract

Male factors account for approximately 50% of reproductive pathology. Different disorders, including urogenital and endocrine system development abnormalities, lead to testicular and gametogenesis defects. Parallely, studies have reported that somatic and germ cell genome decay are a major cause of male infertility. It has been shown that in somatic karyotype, there is a higher incidence of chromosomal aberrations in infertile men than neonatal population and significant chromosome Y microdeletion or specific gene alterations in affected spermatogenesis. Karyotyping and FISH application at somatic and germ cell levels are no longer sufficient to investigate the potential contribution of genome disorders on male infertility. A wide range of molecular methods are required for better understanding of male infertility causes. Molecular omes and omics techniques have become a great tool to investigate male infertility from chromosome to protein. This review reports different molecular tests and methods that can be offered for male infertility investigation.

Keywords::

• investigation and diagnostic
• male infertility
• molecular methods

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilised in the production of this manuscript.

Key issues

• Infertility has been increasing significantly for decades. Male factors account for approximately 50% of the cases, and are mainly related to spermatogenesis failure.

• More than classical cytogenetics investigation at somatic levels, molecular methods are now routinely requested, to investigate male infertility causes.

• Abnormal sperm genome (chromosomal abnormalities or gene defects) can be a major cause of oocyte activation failure, early embryo blocking, implantation failure, abortion and abnormal birth.

• There is clear relation between specific somatic genes mutations and/or defects and sperm parameters.

• Pan genomic methylation profile analysis of sperm DNA showed a global hyper methylation of nearly 10% in men with oligoazoospermia.

• Omes and omics methods application will help to understand the contribution of sperm epigenome immaturity on oocyte activation and fertilization failure.

• Single somatic or germ cell isolation and whole genome amplification will be useful for entire genome analysis and sequencing in reproductive pathology.

• To improve clinical outcomes of assisted reproductive technology program, new molecular methods will change the strategy of genome decays and sperm analysis during male infertility investigation.