SRY-GENE IN THE PATHOGENESIS OF GONADAL DYSGENESIS. SWIER’S SYNDROME

Abstract

Annotation: Swier's syndrome is a genetic disorder, a variant of hypogonadism with a 46 XY karyotype, in which complete or "pure" dysgenesis of the testicles is observed, a female phenotype is formed with a male genotype. It is a congenital disorder associated with the Y chromosome. Swier's syndrome is usually associated with a genetic variant of testicular dysgenesis associated with mutations in the SRY gene (Sex-determining Region Y) located on the Y-chromosome of most mammals, and is involved in the development of the male-type organism (locus Yp11.3). The SRY gene, localized on the short arm of the Y chromosome, is usually expressed by 7-8 weeks of embryogenesis, triggering a signal for the differentiation of Sertoli cells, germinal epithelium of the seminiferous tubules, and Leydig cells. During physiological embryogenesis, AMH (anti-Müllerian hormone) is released in Sertoli cells, leading to regression of the Müllerian ducts, and in Leydig cells stimulated by placental chorionic gonadotropin (CG), and then by their own luteinizing hormone (LH), an increasing amount of testosterone is secreted. The SRY gene encodes the protein TDF (testisdeterminingfactor), a transcription factor that regulates the expression of other genes, which in turn encodes transcription factors that initiate the development of the male reproductive system in the embryonic period. During spermatogenesis during meiosis, the Y chromosome can lose SRY by transferring this gene to the X chromosome. In the absence of full-fledged genetic material (in particular, the expression of the SRY gene), the formation of functionally active testicular tissue is impossible. The lack of secretion of anti-Müllerian hormone leads to the development of Müllerian ducts, from which the uterus, upper vagina and fallopian tubes are formed. Thus, despite the male 46 XY karyotype, the external and internal reproductive organs of the fetus are formed by the female. In this literature review, the defects of the genes responsible for the varieties and clinical manifestations of Swier's syndrome are analyzed.