Persistent Müllerian duct syndrome

Persistent Müllerian duct syndrome (PMDS) is the presence of Müllerian duct derivatives (fallopian tubes, uterus, and/or the upper part of the vagina) in what would be considered a genetically and otherwise physically normal male animal by typical human based standards. In humans, PMDS typically is due to an autosomal recessive congenital disorder and is considered by some to be a form of pseudohermaphroditism due to the presence of Müllerian derivatives.EDAR (EDAR hypohidrotic ectodermal dysplasia) Persistent Müllerian duct syndrome (PMDS) is the presence of Müllerian duct derivatives (fallopian tubes, uterus, and/or the upper part of the vagina) in what would be considered a genetically and otherwise physically normal male animal by typical human based standards. In humans, PMDS typically is due to an autosomal recessive congenital disorder and is considered by some to be a form of pseudohermaphroditism due to the presence of Müllerian derivatives. Typical features include undescended testes (cryptorchidism) and the presence of a small, underdeveloped uterus in an XY infant or adult. This condition is usually caused by deficiency of fetal anti-Müllerian hormone (AMH) effect due to mutations of the gene for AMH or the anti-Müllerian hormone receptor, but may also be as a result of insensitivity to AMH of the target organ. Persistent Mullerian Duct Syndrome (PMDS), also known as Persistent Oviduct Syndrome, is a congenital disorder related to male sexual development. PMDS usually affects phenotypically normal male individuals with the karyotype (46, XY) and is a form of pseudohermaphroditism. PMDS has various causes to do with AMH or receptors abnormalities. For example, AMH has failed to synthesis, failed to release or was secreted at the wrong time. The condition develops in males that consist of normal functioning reproductive organs and gonads, but also female reproductive organs such as the uterus and fallopian tubes. The female reproductive organs origin from a structure from when both genders are still foetuses, called the “Mullerian Duct”. In males, the secretion of ‘Anti-Mullerian Hormone (AMH)’ causes the regression of the Mullerian Duct. Normally, both the Mullerian and Wolffian ducts are present during the 7th week of gestation. Approximately by the end of the 7th and beginning of the 8th week of gestation, the Sertoli cell’s secretion of AMH occur, causing the male sex differentiation during foetal development. The AMH molecules bind to AMHRII (Anti-Mullerian Hormone Receptor Type II) regressing the Mullerian duct. The Leydig cells secrete testosterone to aid male differentiation process by inducing structures such as the epididymis, vas deferens and seminal vesicles. However, with PMDS individuals, the Mullerian Duct persists instead of regressing, due to errors with AMH or the AMH receptor. The problem either coincides with the secretion of AMH (PMDS Type I) or the receptor (PMDS Type II). PMDS is usually coincidentally found during surgery for inguinal hernia, or when the surgeon looks for the reason why the male individual is infertile in adulthood. Another method for the confirmation of PMDS is Genetic Testing. It is not usually preferred because of its processing period and cost. With image screenings such as ultrasounds and MRI, the condition can be efficiently confirmed. Genetic tests can identify those who hold the mutated gene, identify the family member’s chances and risks, and advise those who are trying to get pregnant. Genetic counselling and further genetic testing is offered to confirm the chances and risks of an individual’s offspring obtaining the pair of mutated genes. Further research into the family tree and inheritance is possible as well. An ELISA test is a form of immunoassaying which is a technique consisting of enzymes to identify the presence of particular substances. For PMDS, ELISA tests can be used to determine the levels of AMH within the male individual’s serum, this is only effective before the individual reaches puberty as it normally increases in this period. The result for PMDS patients display low levels of AMH within the serum, and low levels of testosterone. The first visible signs of PMDS after birth is Cryptorchidism (undescended testes) either unilaterally or bilaterally. Along with Cryptorchidism, is also inguinal hernias which may be presented unilaterally (affects one testicle) or bilaterally (affects both testicles). Adults who have been oblivious to this condition may be presented with haematuria, which is when blood appears in urine because of hormonal imbalances. PMDS Type I, is also referred to as ‘Hernia Uteri Inguinalis’, which exhibits one descended testis that has also pulled the fallopian tube and sometimes uterus, through the inguinal canal. The descended testes, fallopian tube and uterus all fall in the same inguinal canal, causing an inguinal hernia. Altogether when the aforementioned conditions occur, it is called ‘Transverse Testicular Ectopia’. Under the microscope, some samples taken for biopsies displayed results where testicular tissue was at a stage of immaturity, and showed dysplasia. Mutation in AMH gene (PMDS Type 1) or AMHR2 gene (PMDS Type 2) are the primary causes of PMDS. AMH, or sometimes referred to as Mullerian Inhibiting Substance (MIS), is secreted by Sertoli cells during an individual’s whole life. It is essential during the foetal period as it functions to regress the Mullerian ducts. However, AMH also functions in the last trimester of pregnancy, after birth, and even during adulthood in minimal amounts. The Sertoli cells in males secrete AMH, through the presence of a Y chromosome. The role of the AMH gene in reproductive development, is the production of a protein that contributes to male sex differentiation. During development of male foetuses, the AMH protein is secreted by cells within the testes. AMHs bind to the AMH Type 2 Receptors, which is present on cells on the surface of the Mullerian Duct. The binding of AMH to its receptors on the Mullerian duct induces the apoptosis of the Mullerian Duct cells, thus the regression of the Mullerian Duct within males. However, for females who originally do not produce AMH proteins during foetal development, the Mullerian Duct eventually becomes the uterus and fallopian Tubes as normal. With the AMH gene mutation (PMDS Type 1), the AMH is either not produced, produced in deficient amounts, defective, secreted at the wrong critical period for male differentiation or the Mullerian ducts manifested a resistance to AMH.