2012-05-19
Determination of microdeletions* of Y chromosome
*missing fragments of Y chromosome causing male infertility.
According to epidemiological data from 10% to 15% of families encounter an infertility problem. Incidence of male infertility is the same as of women infertility. According to Lithuanian study male infertility was diagnosed in 42% of infertile couples. Male infertility is a complex problem, and in many cases the cause of infertility remains unknown. Many and various factors could cause male infertility. These could be genetic causes at the level chromosome and DNA. Microdeletion of Y chromosome (missing fragment of Y chromosome) is one of these causes.
Microdeletion of Y chromosome is diagnosed approximately in 10-15% of males with azoospermia (absence of spermatozoids in sperm) or oligospermia (decreased number o spermatozoids; normal spermatozoid count is > 20 million spermatozoids in 1 mL of sperm). This is one of the common causes of infertility. In case of microdeletion of Y chromosome males are of healthy growth, small testicles are observed in rare cases.
Only cells of males contain Y chromosome. Y chromosome is one of the smallest chromosome of human genome, is makes only 1-1,5% of the length of all chromosomes. This chromosome not only determines gender, but also ensures normal development of sex cells, spermatogenesis. A number of spermatogenesis-relevant genes, generally called azoospermia factor (AZF), are located in the specific region of the long arm of human Y chromosome. Acting synergistically the ensure integrity of the normal spermatogenesis process. When some fragments of AZF region are missing (in case of microdeletion), spermatogenesis disorder occur. Extent of disorder depends on extent of microdeletion, it’s location in the AZF region and adjacent sequences. Therefore phenotype in these cases may manifest in different way. In some instances Y chromosome microdeletions are inherited; however, usually these disorders develop de novo.
According to investigation data, mature spermatozoids are found in testicles of approximately 50% of males with azoospermia and AZF deletion. Using modern technologies these spermatozoids could be collected and used for artificial insemination. However, person should know that his son will inherit Y chromosome with the same microdeletions as in his father’s chromosome.
In SORPO medical research center microdeletions of Y chromosome are determined in male blood or sperm using molecular genetic method, polymerase chain reaction (PCR).
Determination of microdeletion of Y chromosome is not only diagnostic, but also and prognostic method. It is important to determine type of deletion. Moreover, major deletions are associated with more severe disorder of spermatogenesis. Males with azoozpermia and severe oligospermia should primarily be tested for microdeletion of Y chromosome; however, sometimes this abnormality could be found in males with various andrological lesions – varicocele, history of cryptorchism, etc.
It is impossible to detect microdeletions using common karyotype (human chromosome complement) examination. Only major changes of chromosome could be seen in karyotyping. However, in cases of abnormal spermatogenesis karyotyping concomitant along with determination of microdeletion of Y chromosome is recommended; this enables to determine other abnormalities causing infertility.
Blood and sperm specimens are used to determine microdeletions of Y chromosome. Probe sampling is performed daily. Test results are presented in 7-10 days.