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.
History
Vitamin A toxicity is known to be an ancient phenomenon; fossilized skeletal remains of early humans suggest bone abnormalities may have been caused by hypervitaminosis A. There are two theories for hypervitaminosis A in the isolated case of KMN-ER 1808. One of these is the increased consumption of meat and the second is an increase in insect consumption, or Entomophagy.Vitamin A toxicity has long been known to the Inuit as they will not eat the liver of polar bears or bearded seals due to them contain dangerous amounts of Vitamin A. and has been known by Europeans since at least 1597 when Gerrit de Veer wrote in his diary that, while taking refuge in the winter in Nova Zemlya, he and his men became severely ill after eating polar bear liver.In 1913, Antarctic explorers Douglas Mawson and Xavier Mertz were both poisoned (and Mertz died) from eating the livers of their sled dogs during the Far Eastern Party. Another study suggests, however, that exhaustion and diet change are more likely to have caused the tragedy. Other animals
Some Arctic animals demonstrate no signs of hypervitaminosis A despite having 10–20 times the level of vitamin A in their livers as other Arctic animals. These animals are top predators and include the polar bear, Arctic fox, bearded seal, and glaucous gull. This ability to efficiently store higher amounts of vitamin A may have contributed to their survival in the extreme environment of the Arctic. Treatment
These treatments have been used to help treat or manage toxicity in animals.