Complex genetic and semen examination in patients with the disomy Y
Authors: Shtaut M. I. , Solovova O. A. , Sorokina T. M. , Kurilo L. F. , Oparina N. V. , Shilova N. V. , Chukhrova A. L. , Polyakov A. V. , Chernykh V. B. 
Published: November 2023

Background. Among the syndromes with aneuploidy on the sex chromosomes (gonosomes), the Y chromosome dysomy presents the mildest phenotypic manifestation. Most 47,XYY patients are not developed reproductive system abnormalities. Some of them have spermatogenesis defects and in-/subfertility, but the prevalence of male infertility in patients with dysomy Y, is not known. The causes and factors of phenotypic variability, fertility disorders, the spermatogenesis and semen characteristics in patients with dysomy Y have not been sufficiently studied.

Aim. A comprehensive genetic examination, assessment of the state of spermatogenesis and spermatological defects in patients with dysomy Y.

Materials and methods. We examined 25 men with Y-chromosome dysomy. The age of the patients was 32 ± 10 (14–59) years. Chromosome analysis was performed on cultured peripheral blood lymphocytes using a standard cytogenetic method with GTG-staining. Fluorescent in situ hybridization was performed to analyze X and Y chromosomes, gonosomal mosaicism, as well as to evaluate sperm aneuploidy. The Y chromosome microdeletions were detected by multiplex polymerase chain reaction. A standard semen analysis was performed in accordance with the recommendations of the WHO Guidelines (2010). Quantitative karyological analysis of immature germ cells from the ejaculate sediment was performed according to our own previously developed method.

Results. Non-mosaic dysomy Y was diagnosed in 22 patients, including 21 men with karyotype 47,XYY, and one patient with additional chromosomal anomality (Robertson translocation) – karyotype 46,XYY,der(13;14)(q10;q10). XYY/XY mosaicism was revealed in two patients, one has a complex Y chromosome mosaicism with a complete the AZFc (b2/b4) deletion. Pathogenic Y chromosome microdeletions were not found in other patients. In one man, the presence of dysomy Y was suspected according to the results of quantitative fluorescent polymerase chain reaction, but according to the results of cytogenetic examination, the presence of an isodicentric chromosome Yq – karyotype 46,X,psu dic(Y)(p11.3) was detected. Using whole exome sequencing in one azoospermic patient, a heterozygous variant c.653G>A(p.Gly218Asp) was detected in the SYCP2 gene, which encodes one of the proteins of the synaptonemal complex.

Azoospermia  (n = 9,  45 %),  oligoastenoteratozoospermia  (n = 6,  39 %),  asthenoteratozoospermia  (n = 3,  17 %), and asthenozoospermia (n = 2, 11 %) were diagnosed among 20 semen analysed patients. The volume of ejaculate was 2.7 ± 1.7 (1.0–5.0) ml, the concentration and total number of spermatozoa was 14.9 ± 21.8 (0.0–66.25), 50.4 ± 77.7 (0.0–265.0) mil lions, respectively. Oligospermia was observed in 2 (10%) patients. The quantitative karyological analysis of immature germ cells allowed to detect cryptozoospermia in azoospermic patinents and defects of prophase I of meiosis.

Fluorescent in situ hybridization analysis revealed increased sperm aneuploidy (gonosomal dysomy and nullisomy, dysomy 18 and 21).

Conclusion. Most of infertile men with dysomy Y are non-mosaic, and characterized by defected spermatogenesis (non-obstructive azoospermia or oligozoospermia), due to meiotic arrest at prophase I. Pathogenic AZFc deletion was found in a patient with complex Y chromosome mosaicism. Additional genetic factors of male fertility and spermatogenesis defects were found in some patients, which may explain the phenotypic variability.