The Role of Y-Chromosome Microdeletions in Azoospermia and Oligospermia: Genetic Mechanisms, Clinical Consequences, and Diagnostic Approaches

Male infertility represents a major reproductive health concern, with genetic abnormalities, particularly those involving the Y chromosome, contributing substantially to severe defects in spermatogenesis. Among the established genetic causes of non-obstructive azoospermia and severe oligozoospermia, Y chromosome microdeletions are particularly important. These alterations primarily affect the Yq۱۱ region, which contains the three major azoospermia factor (AZF) regions, namely AZFa, AZFb, and AZFc. Most Y chromosome microdeletions are thought to result from non-allelic homologous recombination between highly repetitive sequences, leading to the loss of genes and genomic elements required for normal germ-cell development and sperm production. The clinical consequences vary according to the region and extent of the deletion. Complete deletions involving AZFa or AZFb are typically associated with profound disruption of spermatogenesis and frequently result in azoospermia, whereas AZFc deletions are characterized by greater phenotypic variability, ranging from severe oligozoospermia to complete absence of spermatozoa. Partial deletions within AZFc, especially gr/gr deletions, have also been linked to impaired sperm production and an elevated susceptibility to infertility in specific populations. From a clinical perspective, molecular identification of Y chromosome microdeletions, particularly by sequence-tagged site (STS)-based polymerase chain reaction (PCR), is essential for establishing the genetic basis of male infertility, providing prognostic information, and guiding the selection of appropriate assisted reproductive techniques. This review examines the molecular and genetic mechanisms underlying Y chromosome microdeletions, with emphasis on the structure and characteristics of AZFa, AZFb, and AZFc deletions, their relationships with azoospermia and oligozoospermia, current diagnostic strategies, and their clinical relevance. Existing evidence and ongoing challenges in the diagnosis and clinical management of affected individuals are also addressed.

کلیدواژه ها:

Y chromosome microdeletion ، AZF region ، azoospermia ، oligozoospermia ، spermatogenesis.