Gonadal dysgenesis

Congenital disorder of the reproductive system

Gonadal dysgenesis is classified as any congenital developmental disorder of the reproductive system
in humans. It is atypical development of gonads in an embryo. One type of gonadal dysgenesis is the development of functionless, fibrous tissue, termed streak gonads, instead of reproductive tissue. Streak gonads are a form of aplasia, resulting in hormonal failure that manifests as sexual infantism and infertility, with no initiation of puberty and secondary sex characteristics. Gonadal development is a process, which is primarily controlled genetically by the chromosomal sex (XX or XY), which directs the formation of the gonad (ovary or testicle). At the formation of the developed gonad, steroid production influences local and distant receptors for continued morphological and biochemical changes. Manifestations of gonadal dysgenesis are dependent on the aetiology and severity of the underlying causes. Streak ovaries are present with non functional tissues unable to produce the required sex steroid oestrogen. Low levels of oestrogen effect the HPG axis with no feedback to the anterior pituitary to inhibit the secretion of FSH and LH. If ovarian tissue is present and produces some amount of hormones, limited menstrual cycles can occur. and mutations in steroidogenic acute regulatory protein (StAR protein) which regulates steroid hormone production. In embryogenesis, the development of the male gonads is primarily controlled by the testis determining factor located on the sex determining region of the Y chromosome (SRY). If a single or combination of these genes are mutated or deleted, downstream signalling is disrupted, leading to atypical penis and scrotum. Genital Undermasculinization is the technical term for partial of complete undifferentiated genitallia in individuals with an SRY gene. In utero, all fetuses are anatomically female which are then differentiated via androgen's and SRY activation. Full undermasculinization results in a fully developed vulva with testicles inside the body where the ovaries usually are, which is caused by conditions such as complete androgen insensitivity syndrome. In 5α Reductase 2 deficiency, individuals are born with normal female genitalia, however, during puberty, male differentiation and spermatogenesis occurs. Partial genital undermasculinization can occur if the body has a partial resistance to androgens, or if genital development is blocked, undermasculization can also be induced by certain drugs and hormones. The overall intensity of undermasculinization can manifest itself in hypospadias. The surgical assignment of newborns with ambiguous genitalia to a binary sex for cosmetic purposes is considered a human rights violation. SRY acts on gene SOX9 which drives Sertoli cell formation and testis differentiation. An absence in SRY causes SOX9 to not be expressed at the usual time or concentration, leading to a decreased testosterone and anti Müllerian hormone production. with an unknown causation for the remaining portion of 46,XY gonadal dysgenesis persons. The degree of development of the male reproductive tract is determined by the ratio of germ line cells expressing the XY genotype. giving a chromosomal count of 45, instead of the typical count of 46 chromosomes. Clinical manifestation include primary amenorrhea, hypergonadotropic hypogonadism, streak gonads, infertility, and failure to develop secondary sex characteristics. Hormones are critical for the common events in embryogenesis to occur.

Turner syndrome was first described independently by Otto Ulrich in 1930 and Henry Turner in 1938. 46,XX pure gonadal dysgenesis was first reported in 1960. 46,XY pure gonadal dysgenesis, also known as Swyer syndrome, was first described by Gim Swyer in 1955.