Inadequate levels of testosterone and anti-Müllerian hormone disrupts the development of Wolffian ducts and internal genitalia that are key to male reproductive tract development. The lack of the male associated steroid hormones drives Müllerian duct development and promotes the development of female genitalia.Gonadal streaks replace the tissues of the testes, resembling ovarian stroma absent of follicles. 46,XY gonadal dysgenesis can remain unsuspected until delayed pubertal development is observed.Approximately 15% of cases of 46,XY gonadal dysgenesis carry de novo mutations in the SRY gene,
with an unknown causation for the remaining portion of 46,XY gonadal dysgenesis patients. Mixed gonadal dysgenesis
Mixed gonadal dysgenesis, also known as X0/XY mosaicism or partial gonadal dysgenesis,
is a sex development disorder associated with sex chromosome aneuploidy and mosaicism of the Y chromosome. Mixed gonadal dysgenesis is the presence of two or more germ line cells.The degree of development of the male reproductive tract is determined by the ratio of germ line cells expressing the XY genotype.Manifestations of mixed gonadal dysgenesis are highly variable with asymmetry in gonadal development of testis and streak gonad, accounted for by the percentage of cells expressing XY genotype. The dysgenic testis can have adequate functional tissue to produce satisfactory levels of testosterone to cause masculinisation.Mixed gonadal dysgenesis is poorly understood at the molecular level. The loss of the Y chromosome can occur from deletions, translocations, or migration failure of paired chromosomes during cell division. The chromosomal loss results in partial expression of the SRY gene, giving rise to abnormal development of the reproductive tract and altered hormone levels.
Gonadal dysgenesis is classified as any congenital developmental disorder of the reproductive system
in the male or female. It is the atypical development of the gonads in an embryo,
with reproductive tissue replaced with functionless, fibrous tissue, termed streak gonads. 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 genetically controlled process by the chromosomal sex (XX or XY) which directs the formation of the gonad (ovary or testis).Differentiation of the gonads requires a tightly regulated cascade of genetic, molecular and morphogenic events. At the formation of the developed gonad, steroid production influences local and distant receptors for continued morphological and biochemical changes. This results in the appropriate phenotype corresponding to the karyotype (46,XX for females and 46,XY for males).Gonadal dysgenesis arises from the failure of signalling in this tightly regulated process during early foetal development.Manifestations of gonadal dysgenesis are dependent on the aetiology and severity of the underlying defect. Causes
Pure gonadal dysgenesis 46,XX also known as XX gonadal dysgenesis
Pure gonadal dysgenesis 46,XY also known as XY gonadal dysgenesis
Mixed gonadal dysgenesis also known as partial gonadal dysgenesis, and 45,X/46,XY mosaicism
Turner syndrome also known as 45,X or 45,X0
Endocrine disruptions

Pathogenesis
46,XX gonadal dysgenesis
46,XX gonadal dysgenesis is characteristic of female hypogonadism with a karyotype of 46,XX. Streak ovaries are present with non-functional tissues unable to produce the required sex steroid oestrogen.