Genetic Causes of Human Infertility

Dear Colleagues,

The 2010 Nobel Prize laureate was granted to one of the greatest medical advances of the 20th century, the discovery of in vitro fertilization. With this discovery, other in vitro techniques were developed to circumvent infertility, a medical condition that afflicts a large proportion of humanity, including more than 10% of all couples worldwide. However, the use of these techniques bypasses the diagnosis of the underlying causes of infertility, especially those due to male factors. In addition, its use is not free of potential adverse effects, as it increases the probability of transmitting genetic diseases to offspring.

Male factor infertility by itself contributes to about 40–50% of all infertility cases and affects approximately 7% of the general population. The etiology of this multifactorial disorder of the reproductive system remains unknown in about 40% of patients, and a broad spectrum of genetic and nongenetic factors act mainly at three different levels—pretesticular (Kallmann syndrome), testicular and post-testicular—contribute to this disease.

Genetic causes involve a series of numerical or structural chromosomal abnormalities, such as aneuploidies, the most frequent being Klinfelter’s syndrome (XXY) followed by Y-chromosome disomy, 45X and translocations (Roberstonian); (micro) deletions, such as those involving the Y-chromosome (SRY and AZF); point mutations, such as those in the cystic fibrosis transmembrane conductance regulator (CFTR) gene; and encoding proteins involved in axoneme assembly and organization. Moreover, different gene mutations may have different inheritance patterns (autosomal recessive, autosomal dominant, X-linked or oligogenic inheritance). Nevertheless, over the past few decades, evidence has suggested associations between impaired spermatogenesis and genetic and epigenetic damage in sperm, with possible adverse consequences for offspring.

Genetic causes of male infertility remain underdiagnosed and untreated in many cases, with ~60% of men having idiopathic spermatogenic disruption. Thus, to overcome the scarcity of clear detection and treatment guidelines, specialists must share their studies and develop novel technologies that analyse the genetic factors impacting male factor infertility. Such progress will provide insights into the etiology of male factor infertility and permit the creation of targeted treatments for patients with specific infertile phenotype signatures.

Indeed, genetic screening of male factor infertility is relevant for its diagnostic value, clinical decision making and appropriate genetic counselling.

Moreover, the accurate transmission of gene, chromosomal and epigenetic information has considerable influence on fertility in males and on the fertility of their offspring.

The present Special Issue will focus on a comprehensive synopsis of the (epi)genetic basis of male factor infertility and on the techniques being used to produce new insights in infertility research, determining effective treatments for male patients.

Infertility has pervasive and profound implications for numerous traits of life, health, sustainable development and the economy. In this context, reproductive genetics includes not only prenatal screening, but also the identification of a carrier status. This role in the genetic diagnosis, counselling and treatment of infertile patients is only possible if advances are made towards the clarification of the genetic pathophysiology and the temporal evolution of infertility. This Special Issue focuses on the genetic causes of male infertility. We invite authors to submit manuscripts that study and provide an update on genetic factors associated with male infertility and abnormalities in the male reproductive system.

Dr. Rosália Sá
Guest Editor

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• infertility
• male infertility
• spermatozoa
• epigenetics
• genetic diagnosis
• genetic tests
• male infertility genes
• male infertility phenotypes
• teratozoospermia
• azoospermia
• cryptorchidism
• morphological abnormalities of the sperm flagella