Trisomy 21 or Down syndrome (DS) is one of the most common chromosome abnormalities. Currently, the average life expectancy and social adaptation of DS patients are increasing, and some of them start their own families. Hence, it important to study the state of the reproductive system, gametogenesis and fertility of patients with DS. The spectrum of clinical manifestations of trisomy 21 varies significantly. Men with DS often have severe defects of spermatogenesis, hypogonadotropic hypogonadism, decreased libido and erectile dysfunction, and therefore patients with DS have long been considered infertile. However, there are several reports about the onset of pregnancy and the birth of healthy children from these patients. Due to the high risk of aneuploidy in offspring, as well as ethical and social problems of childbearing, fertility and contraception counseling recommended for DS patients and their guardians.

Background. Severe forms of reproduction disorders are often associated with genetic factors. However, for a number of reasons, medical and genetic examination and counseling of infertile patients are not effective enough, and the contribution of many genetic factors to the genesis of fertility disorders remains insufficiently studied. An integrated approach using various clinical, cytogenetic and molecular genetic methods in the examination makes it possible to improve the diagnosis of genetically determined forms of fertility disorders, in particular those associated with severe azoospermia or oligozoospermia. Aim: improving the effectiveness of medical and genetic examination and counseling of patients with severe azoospermia and oligozoospermia. Methods. The selected sample included 200 men with azoospermia (n=172) and severe oligozoospermia (n=28). The patients underwent clinical, andrological and laboratory-instrumental examination: ultrasound of the scrotum, spermatological, hormonal, cytogenetic, molecular cytogenetic (FISH) and molecular genetic examination of loci or genes associated with male fertility disorders (AZF, CFTR, AR). Results. Various genetic factors of male infertility were found in 99 (49.5%) of 200 patients, including 76 (45.7%) men with azoospermia and 23 (82.1%) patients with severe oligozoospermia. Cystic fibrosis and CBAVD syndrome were diagnosed in 4.5% of patients, congenital hypogonadotropic hypogonadism - in 7.5% of men. Karyotype abnormalities were found in 52 (26.8%) patients, including Klinefelter syndrome (47,XXY; n=34), disomy Y (47,XYY; n=6), 46,XX-testicular disorder of sex development (n=3), balanced autosomal abnormalities (n=9). According to the results of the FISH analysis, no cryptic mosaicism was found in patients with sex chromosomes aneuploidy. Pathogenic Y chromosome microdeletions in the AZF locus (Y q11.2) were found in 16 (8%) patients. Pathogenic variants of the CFTR gene were detected in 9 patients with cystic fibrosis and CBAVD syndrome. Conclusions. Comprehensive genetic examination can significantly improve the effectiveness of the diagnosis of genetically determined forms of male infertility associated with severe pathozoospermia. To identify rare non-syndromic genetic forms of male fertility associated with gene variants and copy number variations, it is necessary to use massive parallel sequencing, array comparative genomic hybridization and other genomic analysis methods.

Individual variability of the ovarian response to hormonal stimulation is one of the most difficult problems in planning an assisted reproductive technologies (ART) therapy. The reasons for the ovarian response variability are not fully determined and can be due to many different factors, including genetic ones. To date, it is known that follicle-stimulating hormone receptor gene polymorphism can have a significant effect on the formation of dominant follicles, including in response to ovarian stimulation therapy. The aim of this investigation was to study the association of follicle-stimulating receptor gene genetic variant FSHR c.2039A>G [rs6166] with hypothalamic-pituitary-gonadal hormones serum levels and the degree of ovarian response to hormonal stimulation in women undergoing ART therapy. The study involved 141 women who underwent IVF at the Center for Human Reproduction and IVF in Rostov-on-Don, including 67 patients with a normal ovarian response (8-20 follicles), 58 with a poor response (<8 follicles) and 16 with a hyper response (> 20 follicles) to hormonal stimulation. Patients were stratified according to the number of punctured follicles >13mm. Total estimation of genotype frequencies for FSHR c.2039A>G genetic variant was: AA (41,9%), AG (39,0%), GG (19,1%); in women with normal ovarian response: AA (41,8%), AG (41,8%), GG (16,4%); in women with poor ovarian response: AA (37,9%), AG (39,7%), GG (22,4%); in women with hyper response to ovarian stimulation: AA (62,4%), AG (18,8%), GG (18,8%). An association of the FSHR c.2039A>G genetic variant with the ovarian response and hypothalamic-pituitary-gonadal hormones serum levels was revealed. It was shown that FSHR 2039GG genotype is associated with higher basal follicle-stimulating hormone (FSH) level, and A allele is associated with the fewer follicles number maturation. Genotype FSHR 2039GG is also associated with higher basal luteinizing hormone (LH) and progesterone levels. Women with FSHR 2039 AA genotype had higher the day trigger administration estradiol serum level.

Targeted drugs for the treatment of oncological diseases, in particular, the inhibitors of Sunitinib and Sorafenib, are widely used in oncological practice and the study of the peculiarities of their application is very relevant. On the models of cultured cancer cells in vitro it was shown that kinase inhibitors are able to strengthen the expression of tumor progression genes (SNAI1, SNAI2, CD44, CDH1, CLDN1) associated with the epithelial-mesenchymal transition (EMT). The activation of such genes is shown under the action of low doses of tyrosine kinase inhibitors - Sunitinib and Sorafenib. The activation of the studied genes was different in different cultures and depended on the applied drug. It was assumed that due to the local uneven distribution of drugs in tissues of the tumor, kinase inhibitors may be one of the reasons for activating the expression of genes associated with the epithelial- mesenchymal transition, and thus contribute to its progression.

Introduction. Robertsonian translocations (RT) are the most common balanced chromosomal abnormalities. RT carriers may have an increased risk of reproductive disorders (infertility, pregnancy loss and chromosomal abnormalities/multiple congenital abnormalities in offspring), but the mechanisms of gametogenesis and fertility disorders are still under consideration. Aim: to evaluate semen parameters and meiosis in infertile male RT carriers. Methods. 21 men from infertile couples, RT carriers, were examined: rob(13;14), (n=16), rob(13;15) (n=3), rob(13;21) (n=1) and rob(14;15) (n=1). Chromosome analysis was performed according to a standard cytogenetic procedure using GTG staining. Semen analysis was done for all the patients, and for 5 patients with RT (13;14) quantitative karyological analysis of immature germ cells was done (QKA IGC). Results. Abnormal semen parameters were detected in all the men examined, with severe forms of pathozoospermia prevailing: oligoastenotheratozoospermia (81%, n=17) and azoospermia (14%, n=3); asthenotheratozoospermia was detected in one patient (5%). The QKA IGC revealed the mechanism of spermatogenesis failure - a partial arrest of spermatogenesis at the pre- pachytene stages and in the pachytene of prophase I of meiosis in oligozoospermic samples; and the absence of meiotic arrest in semen with normal sperm concentration. Conclusions. Subfertility in examined male RT carriers is associated with pathozoospermia and in most patients is caused by a partial arrest of spermatogenesis in prophase I of meiosis, which leads to a decrease in the number of spermatozoa (oligozoospermia) or their absence (azoospermia).

Nephrotic syndrome (NS) with variants in the CRB2 gene is a rather rare condition, and there are only a few reports of its severe course and no one of mild one. The aim of the communication is to demonstrate the phenotypic features of nephrotic syndrome caused by mutations in the CRB2 gene. On the basis of the nephrological and molecular-genetic departments of the Federal State Autonomous Institution “National Medical Research Center of Children’s Health” we performed retro- and prospective study of the genetic causes of primary steroid-resistant nephrotic syndrome, included 250 children. Among 250 children, only two had causative nucleotide variants in the CRB2 gene (0.8% of all children with steroid-resistant and 1.21% of children with identified genetic causes of SRNS). Children had a different course of the disease and the severity of extrarenal manifestations

Y chromosome microdeletions in the AZF/Yq11.2 locus («azoospermia factor») are a common genetic cause of male infertility associated azoospermia and severe oligozoospermia. Complete AZFb region deletions are characterized by azoospermia due to severe spermatogenesis defects (meiotic arrest at prophase I and Sertoli cell-only syndrome), while it is impossible to obtain sperm suitable for in vitro fertilization, neither from the ejaculate, no from testicular biopsy. This article describes severe oligoastenoteratozoospermic patient with distal AZFb region deletion. According to the results of chromosome analysis, the patient had a normal male karyotype (46,XY). Multiplex PCR revealed an absence of sY127, sY134 и sY142 loci, that is characteristic for complete AZFb deletion. High-resolution array comparative genomic hybridization (arrayCGH) allowed to detect CNV (copy number variant) in Yq11.222-q11.223 loci, which is 3.5 Mb deletion (20.583.738-24.094.882), partially deleting the AZFb region. Apparently, the deletion occurred as a result of unbalanced recombination of amplicons b1 and b5. Few oligozoospermic men with various types of AZFb deletions have been reported in the literature. The presented case and previously reported patients with Y-chromosome microdeletions indicate the possibility of sperm retrieval of spermatozoa suitable for IVF/ICSI in some patients with complete and partial AZFb and AZFb+c deletions in partial preservation of spermatogenesis. In this regard, as well as the possibility of falsely positive and or incorrectly defined AZF deletions, it is need to highly recommend to verify various deletions with the (sub)typing when Y chromosome microdeletions were detected.