AZF Microdeletions
A test for detecting deletions in the AZF locus by polymerase chain reaction.
Male infertility
Male infertility is a reproductive disorder characterized by the inability to conceive a baby after 12 months of regular sexual activity without the use of contraceptives.
Idiopathic form of male infertility means that there is no known etiologic factor causing reproductive dysfunction. Factors associated with male infertility are genetic and endocrine abnormalities, infectious inflammatory diseases of the urogenital tract, erectile or ejaculatory dysfunctions, congenital or acquired malformations of genitourinary organs, malignant neoplasms, and immunologic disorders.
The main tool for assessing male fertility is the spermogram; however, it cannot establish the precise etiology of the disease. Genetic defects can be the cause of impaired spermatogenesis. According to clinical recommendations of the Ministry of Health of the Russian Federation “Male infertility” (2021), patients with azoospermia and oligozoospermia are advised to get tested for microdeletions in the AZF (azoospermia factor) locus of the Y-chromosome using molecular genetic methods.
The AZF locus is located in the euchromatin region of the Y chromosome long arm mapped on chromosomal segment Yq11.22-23, and includes a large number of genes responsible for sperm formation and development.
AZF locus deletions are the second most common genetic cause of male infertility (after karyotype abnormalities). Microdeletions of the Y-chromosome locus are found in 10-15% of all azoospermia patients and in 5-10% of severe oligozoospermia cases. AZF locus deletions are associated with varying degrees of spermatogenesis dysfunction, which has high diagnostic and prognostic value for TESE (testicular sperm extraction). TESE is contraindicated in case of a complete AZFa and/or AZFb locus deletion.
The AZF locus contains three subregions (AZFa, AZFb, AZFc), with each of them containing genes responsible for spermatogenesis.
AZFa
Deletions in the AZFa subregion account for approximately 5% of all Y chromosome microdeletions and result in complete germ cell aplasia in the seminiferous tubules (known as the Sertoli Cell-Only Syndrome). This is an irreversible condition characterized by the absence of sperm in the ejaculate (azoospermia). In case of complete deletion of the AZFa subregion, sperm isolation procedures are not recommended, as the outcome of sperm aspiration from testicular tissue for men with this type of deletion is extremely unfavorable.
AZFb
Deletions in the AZFb subregion account for around 16% of all Y chromosome microdeletions. The high-copy-number RBMY gene is located in this subregion. When one or more copies of the RBMY gene are deleted, patients develop azoospermia or severe oligozoospermia. The absence of the AZFb subregion leads to severe spermatogenesis dysfunctions with a high risk of developing Sertoli Cell-Only Syndrome.
AZFc
Deletions in the AZFc subregion account for up to 60% of all Y chromosome microdeletions. The DAZ (Deleted in Azoospermia) gene family is located in this subregion. Patients may present with Sertoli Cell-Only Syndrome type 2, characterized a small amount of spermatogenic cells in the seminiferous tubules. A gr/gr deletion can also take place in the AZFc subregion. With this deletion, half of the AZFc subregion is lost. Carriers of gr/gr deletions have a 7-fold increased risk of oligozoospermia. In addition, some evidence suggests that the presence of this deletion increases the risk of developing testicular germ cell tumors.
Microdeletions of several Y chromosome subregions at once are found in 15% of cases. Spermogram-based analysis of the reproductive system function confirmed that the presence of microdeletions affecting more than one subregion, azoospermia and Sertoli Cell-Only syndrome are observed in nearly 100% of cases.
Indications for testing
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Azoospermia -
Severe oligozoospermia -
Spermatogenesis dysfunctions -
Ineffectiveness of assisted reproductive technologies -
Family history of infertility -
Planning treatment for infertility -
Hypogonadism of unclear etiology -
Abnormalities of genital development -
Assessment of fertility disorder risks in male offsprings of individuals with AZF deletions
AZF Microdeletions
DNA-Technology developed a kit (see Tables 37-39) for detecting AZF deletions associated with male infertility. The analytical panel included 13 nonpolymorphic markers that allow detecting deletions in all AZF loci.
Sample: peripheral blood.
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