The genetic causes of male factor infertility: A review

A multi-faceted approach to understanding male infertility: gene mutations, molecular defects and assisted reproductive techniques (ART)

“…In all carriers, reciprocal translocations have impacted spermatogenesis, demonstrated by poor sperm quality or sperm aneuploidies, severe azoospermia and infertility. Although carriers of RT may exhibit a normal phenotype, spermatogenesis in male carriers of RT is variably affected, ranging from normal to oligoasthenospermia or azoospermia [17,30]. It is thereby of paramount importance to analyze the chromosomal constitution in the sperm of RT carriers, in order to provide preimplantation genetic diagnosis and adaptive genetic counseling to persons undergoing IVF treatment.…”

“…While deletions or small mutations in USP9Y seem to be associated with severe hypo-spermatogenesis only, patients with deletions of DBY may present with a combination of the two: sertoli cell-only syndrome (SCOS), a condition characterized by the presence of complete Sertoli cells in the testes but a lack of spermatozoa in the ejaculate and severe hypospermatogenesis [17,48]. On the contrary, patients with deletions of both USP9Y and DBY seem to invariably demonstrate azoospermia with a testicular histology of SCOS [17,49]. Deletion of the USP9Y gene can additionally cause azoospermia, oligozoospermia, or oligoasthenozoospermia [15,50].…”

“…Recently, studies have revealed that in cases where all the genes in the AZFb region excluding RBMY and PRY are deleted, patients present with hypo spermatogenesis [20]. However, if both the RBMY and PRY genes are removed, spermatogenesis is arrested completely, indicating that RBMY and PRY are the major genes involved in fertility [17,34].…”

“…Such structures may undergo frequent inversion and gene-conversion events [61], as well as duplications and deletions [62]. These small partial deletions or sub-deletions produce a wide array of phenotypes, ranging from normospermic to azoospermic, aided by their interaction with the environment and their genetic background [17]. The gr/gr, b1/b3, and g1/g3 (b2/b3) are the most frequent sub deletions in the AZFc region of the Y chromosome [63] (Fig.…”

“…Whereas many other genetic abnormalities that cause male infertility are still unknown, it is likely that most cases of idiopathic infertility could be accounted for by underlying genetic causes [16]. Molecular defects and genetic alterations responsible for male infertility disrupt physiological processes including hormonal homeostasis, spermatogenesis and sperm quality [17,18]. Chromosomal abnormalities, single gene point mutations including mutation of cystic fibrosis transmembrane receptor gene (CFTR), polygenic or multifactorial genetic defects including Y chromosome deletions or micro deletions, mitochondrial DNA (mtDNA) mutations, endocrine disorders of genetic origin are the most frequently reported genetic causes of male infertility ( Table 2).…”