Persistent Mullerian duct syndrome
Encyclopedia
Persistent Müllerian duct syndrome (PMDS) refers to the presence of a uterus
and sometimes other Müllerian duct
derivatives in a male
animal. 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 uterine tissue.
Typical features include undescended testes (cryptorchidism
) and the presence of a small, underdeveloped uterus in a male infant or adult. This condition is usually caused by deficiency of fetal anti-Müllerian hormone
(AMH) effect due to mutation
s of the gene
for AMH or the anti-Müllerian hormone receptor
.
as one of the earliest Sertoli cell products and induces regression of the Müllerian ducts. Müllerian ducts are only sensitive to AMH action around the 8th week of amenorrhea and Müllerian regression is completed by the end of the 9th week. The AMH induced regression of the Müllerian duct occurs in cranio-caudal direction via apoptosis. The AMH receptors are located on the Müllerian duct mesenchyme and transfer the apoptotic signal to the Müllerian epithelial cell presumably via paracrine actors. The Wolffian ducts differentiate into epididymides, vasa deferentia and seminal vesicles under the influence of testosterone, produced by the fetal Leydig cell
s and Müllerian duct
s begin to develop, the tissues are often intertwined, resulting in obstruction or nonpatency of the vas deferens
or other parts of the male excretory ducts. This can result in infertility
, the most serious potential problem caused by this condition.
Cryptorchidism in AMH deficiency suggests that AMH may play a role in transabdominal testicular descent, perhaps by facilitating contraction of the gubernaculum
.
Other Müllerian derivatives which may be present in at least a rudimentary form are the cervix
, upper part of the vagina
, and fallopian tube
s.
The condition can come to attention because of a bulge in the inguinal canal
of a male infant due to hernia
tion of the uterus. The presence of a uterus may be noticed if an ultrasound
or MRI
of the pelvis
is performed to locate the testes or for other reasons. Occasionally the uterus is discovered during abdominal
surgery
for some other purpose in later childhood or adult life.
Although persistent Müllerian duct syndrome is classified as an intersex
condition, it does not involve ambiguity or malformation of the external genitalia.
Apart from humans, this syndrome has been reported in dogs.
) to retrieve the testes and position them in the scrotum
is the primary treatment. Occasionally they are unsalvageable if located high in the retroperitoneum
. During this surgery, the uterus is usually removed and attempts made to dissect away Müllerian tissue from the vas deferens
and epididymis
for the purpose of improving the chance of fertility. Testosterone
replacement will be necessary at puberty
if the testes cannot be rescued. Lately, laparascopic hysterectomy
is offered to patients as a solution to both improve the chances of fertility and to prevent the occurrences of neoplastic tissue formation.
s of the gene (AMH) for AMH on chromosome
19p3.3.
PMDS type II results from mutations of the gene (AMH-RII) for the AMH receptor on 12q13.
Both types of disorders are inherited as autosomal recessive conditions with expression limited to males (as females with AMH deficiency have no identified problems).
Uterus
The uterus or womb is a major female hormone-responsive reproductive sex organ of most mammals including humans. One end, the cervix, opens into the vagina, while the other is connected to one or both fallopian tubes, depending on the species...
and sometimes other Müllerian duct
Müllerian duct
Müllerian ducts are paired ducts of the embryo that run down the lateral sides of the urogenital ridge and terminate at the Müllerian eminence in the primitive urogenital sinus. In the female, they will develop to form the Fallopian tubes, uterus, cervix, and the upper two-third of the vagina; in...
derivatives in a male
Male
Male refers to the biological sex of an organism, or part of an organism, which produces small mobile gametes, called spermatozoa. Each spermatozoon can fuse with a larger female gamete or ovum, in the process of fertilization...
animal. In humans, PMDS typically is due to an autosomal recessive
Recessive
In genetics, the term "recessive gene" refers to an allele that causes a phenotype that is only seen in a homozygous genotype and never in a heterozygous genotype. Every person has two copies of every gene on autosomal chromosomes, one from mother and one from father...
congenital disorder
Congenital disorder
A congenital disorder, or congenital disease, is a condition existing at birth and often before birth, or that develops during the first month of life , regardless of causation...
and is considered by some to be a form of pseudohermaphroditism
Pseudohermaphroditism
Pseudohermaphroditism, or pseudo-hermaphroditism, is the condition in which an organism is born with secondary sex characteristics or a phenotype that is different from what would be expected on the basis of the gonadal tissue ....
due to the presence of uterine tissue.
Typical features include undescended testes (cryptorchidism
Cryptorchidism
Cryptorchidism is the absence of one or both testes from the scrotum. It is the most common birth defect regarding male genitalia. In unique cases, cryptorchidism can develop later in life, often as late as young adulthood. About 3% of full-term and 30% of premature infant boys are born with at...
) and the presence of a small, underdeveloped uterus in a male infant or adult. This condition is usually caused by deficiency of fetal anti-Müllerian hormone
Anti-müllerian hormone
Anti-Müllerian hormone also known as AMH is a protein that, in humans, is encoded by the AMH gene. It inhibits the development of the Müllerian ducts in the male embryo. It has also been called Müllerian inhibiting factor , Müllerian-inhibiting hormone , and Müllerian-inhibiting substance...
(AMH) effect due to mutation
Mutation
In molecular biology and genetics, mutations are changes in a genomic sequence: the DNA sequence of a cell's genome or the DNA or RNA sequence of a virus. They can be defined as sudden and spontaneous changes in the cell. Mutations are caused by radiation, viruses, transposons and mutagenic...
s of the gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
for AMH or the anti-Müllerian hormone receptor
Anti-Mullerian hormone receptor
Anti-Müllerian hormone receptor is a receptor for anti-Müllerian hormone.-Pathology:The anti-Mullerian hormone receptor can be responsible for persistent Müllerian duct syndrome.-External links:...
.
Background
AMH (Anti Müllerian Hormone) is produced by the primitive Sertoli cellSertoli cell
A Sertoli cell is a 'nurse' cell of the testes that is part of a seminiferous tubule.It is activated by follicle-stimulating hormone and has FSH-receptor on its membranes.-Functions:...
as one of the earliest Sertoli cell products and induces regression of the Müllerian ducts. Müllerian ducts are only sensitive to AMH action around the 8th week of amenorrhea and Müllerian regression is completed by the end of the 9th week. The AMH induced regression of the Müllerian duct occurs in cranio-caudal direction via apoptosis. The AMH receptors are located on the Müllerian duct mesenchyme and transfer the apoptotic signal to the Müllerian epithelial cell presumably via paracrine actors. The Wolffian ducts differentiate into epididymides, vasa deferentia and seminal vesicles under the influence of testosterone, produced by the fetal Leydig cell
Presentation
Because both the Wolffian ductWolffian duct
The mesonephric duct is a paired organ found in mammals including humans during embryogenesis....
s and Müllerian duct
Müllerian duct
Müllerian ducts are paired ducts of the embryo that run down the lateral sides of the urogenital ridge and terminate at the Müllerian eminence in the primitive urogenital sinus. In the female, they will develop to form the Fallopian tubes, uterus, cervix, and the upper two-third of the vagina; in...
s begin to develop, the tissues are often intertwined, resulting in obstruction or nonpatency of the vas deferens
Vas deferens
The vas deferens , also called ductus deferens, , is part of the male anatomy of many vertebrates; they transport sperm from the epididymis in anticipation of ejaculation....
or other parts of the male excretory ducts. This can result in infertility
Infertility
Infertility primarily refers to the biological inability of a person to contribute to conception. Infertility may also refer to the state of a woman who is unable to carry a pregnancy to full term...
, the most serious potential problem caused by this condition.
Cryptorchidism in AMH deficiency suggests that AMH may play a role in transabdominal testicular descent, perhaps by facilitating contraction of the gubernaculum
Gubernaculum
The paired Gubernacula are embryonic structures which begin as undifferentiated mesenchyme attaching to the caudal end of the gonads .-Function during development:...
.
Other Müllerian derivatives which may be present in at least a rudimentary form are the cervix
Cervix
The cervix is the lower, narrow portion of the uterus where it joins with the top end of the vagina. It is cylindrical or conical in shape and protrudes through the upper anterior vaginal wall...
, upper part of the vagina
Vagina
The vagina is a fibromuscular tubular tract leading from the uterus to the exterior of the body in female placental mammals and marsupials, or to the cloaca in female birds, monotremes, and some reptiles. Female insects and other invertebrates also have a vagina, which is the terminal part of the...
, and fallopian tube
Fallopian tube
The Fallopian tubes, also known as oviducts, uterine tubes, and salpinges are two very fine tubes lined with ciliated epithelia, leading from the ovaries of female mammals into the uterus, via the utero-tubal junction...
s.
The condition can come to attention because of a bulge in the inguinal canal
Inguinal canal
The inguinal canal is a passage in the anterior abdominal wall which in men conveys the spermatic cord and in women the round ligament. The inguinal canal is larger and more prominent in men.-Site:...
of a male infant due to hernia
Hernia
A hernia is the protrusion of an organ or the fascia of an organ through the wall of the cavity that normally contains it. A hiatal hernia occurs when the stomach protrudes into the mediastinum through the esophageal opening in the diaphragm....
tion of the uterus. The presence of a uterus may be noticed if an ultrasound
Ultrasound
Ultrasound is cyclic sound pressure with a frequency greater than the upper limit of human hearing. Ultrasound is thus not separated from "normal" sound based on differences in physical properties, only the fact that humans cannot hear it. Although this limit varies from person to person, it is...
or MRI
Magnetic resonance imaging
Magnetic resonance imaging , nuclear magnetic resonance imaging , or magnetic resonance tomography is a medical imaging technique used in radiology to visualize detailed internal structures...
of the pelvis
Pelvis
In human anatomy, the pelvis is the lower part of the trunk, between the abdomen and the lower limbs .The pelvis includes several structures:...
is performed to locate the testes or for other reasons. Occasionally the uterus is discovered during abdominal
Abdomen
In vertebrates such as mammals the abdomen constitutes the part of the body between the thorax and pelvis. The region enclosed by the abdomen is termed the abdominal cavity...
surgery
Surgery
Surgery is an ancient medical specialty that uses operative manual and instrumental techniques on a patient to investigate and/or treat a pathological condition such as disease or injury, or to help improve bodily function or appearance.An act of performing surgery may be called a surgical...
for some other purpose in later childhood or adult life.
Although persistent Müllerian duct syndrome is classified as an intersex
Intersex
Intersex, in humans and other animals, is the presence of intermediate or atypical combinations of physical features that usually distinguish female from male...
condition, it does not involve ambiguity or malformation of the external genitalia.
Apart from humans, this syndrome has been reported in dogs.
Treatment
Surgery (orchiopexyOrchiopexy
Orchiopexy is a surgery to move an undescended testicle into the scrotum and permanently fix it there. It is performed by a pediatric urologist or surgeon on boys with cryptorchidism, typically before they reach the age of two...
) to retrieve the testes and position them in the scrotum
Scrotum
In some male mammals the scrotum is a dual-chambered protuberance of skin and muscle containing the testicles and divided by a septum. It is an extension of the perineum, and is located between the penis and anus. In humans and some other mammals, the base of the scrotum becomes covered with curly...
is the primary treatment. Occasionally they are unsalvageable if located high in the retroperitoneum
Retroperitoneum
The retroperitoneal space is the anatomical space in the abdominal cavity behind the peritoneum. It has no specific delineating anatomical structures...
. During this surgery, the uterus is usually removed and attempts made to dissect away Müllerian tissue from the vas deferens
Vas deferens
The vas deferens , also called ductus deferens, , is part of the male anatomy of many vertebrates; they transport sperm from the epididymis in anticipation of ejaculation....
and epididymis
Epididymis
The epididymis is part of the male reproductive system and is present in all male amniotes. It is a narrow, tightly-coiled tube connecting the efferent ducts from the rear of each testicle to its vas deferens. A similar, but probably non-homologous, structure is found in cartilaginous...
for the purpose of improving the chance of fertility. Testosterone
Testosterone
Testosterone is a steroid hormone from the androgen group and is found in mammals, reptiles, birds, and other vertebrates. In mammals, testosterone is primarily secreted in the testes of males and the ovaries of females, although small amounts are also secreted by the adrenal glands...
replacement will be necessary at puberty
Puberty
Puberty is the process of physical changes by which a child's body matures into an adult body capable of reproduction, as initiated by hormonal signals from the brain to the gonads; the ovaries in a girl, the testes in a boy...
if the testes cannot be rescued. Lately, laparascopic hysterectomy
Hysterectomy
A hysterectomy is the surgical removal of the uterus, usually performed by a gynecologist. Hysterectomy may be total or partial...
is offered to patients as a solution to both improve the chances of fertility and to prevent the occurrences of neoplastic tissue formation.
Molecular genetics and inheritance
PMDS type I results from mutationMutation
In molecular biology and genetics, mutations are changes in a genomic sequence: the DNA sequence of a cell's genome or the DNA or RNA sequence of a virus. They can be defined as sudden and spontaneous changes in the cell. Mutations are caused by radiation, viruses, transposons and mutagenic...
s of the gene (AMH) for AMH on chromosome
Chromosome
A chromosome is an organized structure of DNA and protein found in cells. It is a single piece of coiled DNA containing many genes, regulatory elements and other nucleotide sequences. Chromosomes also contain DNA-bound proteins, which serve to package the DNA and control its functions.Chromosomes...
19p3.3.
PMDS type II results from mutations of the gene (AMH-RII) for the AMH receptor on 12q13.
See also
- IntersexIntersexIntersex, in humans and other animals, is the presence of intermediate or atypical combinations of physical features that usually distinguish female from male...
- Sexual differentiationSexual differentiationSexual differentiation is the process of development of the differences between males and females from an undifferentiated zygote...
- CryptorchidismCryptorchidismCryptorchidism is the absence of one or both testes from the scrotum. It is the most common birth defect regarding male genitalia. In unique cases, cryptorchidism can develop later in life, often as late as young adulthood. About 3% of full-term and 30% of premature infant boys are born with at...
- Anti-müllerian hormoneAnti-müllerian hormoneAnti-Müllerian hormone also known as AMH is a protein that, in humans, is encoded by the AMH gene. It inhibits the development of the Müllerian ducts in the male embryo. It has also been called Müllerian inhibiting factor , Müllerian-inhibiting hormone , and Müllerian-inhibiting substance...