Molecular Mechanisms of Male Infertility

Dear Colleagues,

Infertility affects approximately 15% of the couples wanting to conceive and seek medical treatment for fertility, and in 50%, a male infertility-associated factor is found, together with abnormal semen parameters. In 30–40% of these cases, the etiology of male infertility remains unknown and is called idiopathic male infertility. In addition, male infertility, which accounts for approximately 50% of the cases of infertility among couples, is gradually leading to depression and other psychological outcomes, and this might be a potential sign of serious future consequences. Moreover, human spermatogenesis (HS) is an intricate network of sequential processes responsible for the production of the male gamete, the spermatozoon.

In fact, male infertility is an extremely complex disorder that is contributed to by genetics, the environment, or a combination of both. Lifestyle and environmental factors cause an increase in sperm DNA fragmentation (SDF) and consequently infertility.

In the last two decades, significant advances have been made in the studies of the molecular mechanisms of spermatogenesis and male infertility due to the advances in miRNAs, RNA , whole genome sequencing, transcriptome profiling, DNA methylation, and genome structure analysis of chromatin. Recently, there has been a lot of emphasis placed on the importance of new next-generation sequencing technologies for studying the genome and epigenome mechanisms, transcriptome, proteome, and metabolome of ejaculate. An adequate (epi)genetic diagnosis of male infertility is of major importance to evaluate if a genetic abnormality will be transmitted to the offspring.

Additionally, the proteomic analysis of seminal plasma proteome could also provide important biomarkers of oxidative stress in spermatozoa. In addition, metabolomic profiling of key biomarkers and their potential role in this rapid, non-invasive analysis give a new insight in the investigation of infertile men. More recently, the technique for studying the relationship between obesity and male infertility, focusing on the molecular mechanisms through which it negatively affects spermatogenesis, sperm quality, and male reproduction, has been investigated in various laboratories.

These techniques and others have helped identify novel infertility causes. Also, male infertility is a complex, multi-factorial disorder, and the underlying causes often remain unknown. Further research on the (epi)genetic and molecular defects in spermatogenesis and sperm function is necessary to improve the diagnosis and develop more personalized treatments for infertile men. It has been suggested that epigenetic dysregulation can be involved in the etiology of idiopathic male infertility.

Research areas may include (but are not limited to) the following:

• Endogenous and exogenous physical, chemical, and biological sources modify the genome of spermatozoa;
• Sperm chromatin and implications for male infertility;
• Molecular and structural basis of the histone-to-protamine exchange;
• Post-translational modifications on P1 and P2 protamines;
• DNA damage and DNA repair mechanisms in male infertility;
• Extrinsic factors such as smoking, cannabis,
• Redox signaling pathways in spermatozoa, which, in turn, may affect its physiological functions;
• Methylation and hyper- and hypo-methylation of specific DNA regions.
• miRNAs as biomarkers to understand the molecular mechanisms underlying male infertility;
• Molecular mechanisms of obesity and male infertility;
• Proteome studies of spermatozoa from fertile and infertile men.

Dr. Mohamed Hammadeh
Dr. Houda Amor
Guest Editors

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• male infertility
• microRNA
• NGS
• molecular mechanism