Paramesonephric ducts (or Müllerian ducts) are paired ducts of the

embryo An embryo is an initial stage of development of a multicellular organism. In organisms that reproduce sexually, embryonic development is the part of the life cycle that begins just after fertilization of the female egg cell by the male spe ...

that run down the lateral sides of the

genital ridge The genital ridge (or gonadal ridge) is the precursor to the gonads. The genital ridge initially consists mainly of mesenchyme and cells of underlying mesonephric origin. Once oogonia enter this area they attempt to associate with these somatic cel ...

and terminate at the

sinus tubercle Sinus tubercle (also known as sinual tubercle or Müllerian eminence) is the proliferation of endoderm induced by the paramesonephric ducts. It is located in the developing fetus between the orifices of the mesonephric ducts on the urogenital s ...

in the primitive urogenital sinus. In the female, they will develop to form the

fallopian tube The fallopian tubes, also known as uterine tubes, oviducts or salpinges (singular salpinx), are paired tubes in the human female that stretch from the uterus to the ovaries. The fallopian tubes are part of the female reproductive system. In ot ...

uterus The uterus (from Latin ''uterus'', plural ''uteri'') or womb () is the organ in the reproductive system of most female mammals, including humans that accommodates the embryonic and fetal development of one or more embryos until birth. The uter ...

cervix The cervix or cervix uteri (Latin, 'neck of the uterus') is the lower part of the uterus (womb) in the human female reproductive system. The cervix is usually 2 to 3 cm long (~1 inch) and roughly cylindrical in shape, which changes during ...

, and the upper one-third of the

vagina In mammals, the vagina is the elastic, muscular part of the female genital tract. In humans, it extends from the vestibule to the cervix. The outer vaginal opening is normally partly covered by a thin layer of mucosal tissue called the hymen ...

Development

The

female reproductive system The female reproductive system is made up of the internal and external sex organs that function in the reproduction of new offspring. In humans, the female reproductive system is immature at birth and develops to maturity at puberty to be ...

is composed of two embryological segments: the urogenital sinus and the paramesonephric ducts. The two are conjoined at the

. Paramesonephric ducts are present on the embryo of both sexes. Only in females do they develop into reproductive organs. They degenerate in males of certain species, but the adjoining

mesonephric duct The mesonephric duct (also known as the Wolffian duct, archinephric duct, Leydig's duct or nephric duct) is a paired Organ (anatomy), organ that forms during the embryonic development of humans and other mammals and gives rise to male Sex organ, r ...

s develop into male reproductive organs. The sex based differences in the contributions of the paramesonephric ducts to reproductive organs is based on the presence, and degree of presence, of

Anti-Müllerian hormone Anti-Müllerian hormone (AMH), also known as Müllerian-inhibiting hormone (MIH), is a glycoprotein hormone structurally related to inhibin and activin from the transforming growth factor beta superfamily, whose key roles are in growth differen ...

. During the formation of the reproductive system, the paramesonephric ducts are formed just lateral to the

mesonephric ducts The mesonephric duct (also known as the Wolffian duct, archinephric duct, Leydig's duct or nephric duct) is a paired organ that forms during the embryonic development of humans and other mammals and gives rise to male reproductive organs. Stru ...

in both female and male embryos 6 weeks after fertilization. During this time primordial

germ cells Germ or germs may refer to: Science * Germ (microorganism), an informal word for a pathogen * Germ cell, cell that gives rise to the gametes of an organism that reproduces sexually * Germ layer, a primary layer of cells that forms during embryo ...

migrate from the yolk sac to the

; a region of

mesenchyme Mesenchyme () is a type of loosely organized animal embryonic connective tissue of undifferentiated cells that give rise to most tissues, such as skin, blood or bone. The interactions between mesenchyme and epithelium help to form nearly every o ...

arising from, and running parallel with, the

mesonephros The mesonephros ( el, middle kidney) is one of three excretory system, excretory organs that develop in vertebrates. It serves as the main excretory organ of aquatic vertebrates and as a temporary kidney in reptiles, birds, and mammals. The mesone ...

. The paramesonephric ducts are formed by the craniocaudal invagination of a ribbon of thickened coelomic epithelium that extends from the third thoracic segment caudally to the posterior wall of the urogenital sinus. The caudal parts of the paramesonephric ducts fuse into a single tube, known as the uterovaginal primordium, before flowing into the dorsal aspect of the

urogenital sinus The urogenital sinus is a part of the human body only present in the development of the urinary and reproductive organs. It is the ventral part of the cloaca, formed after the cloaca separates from the anal canal during the fourth to seventh w ...

at the

directly medial to the

Anti-Müllerian hormone

The development of the paramesonephric (Müllerian) ducts is controlled by the presence or absence of

anti-Müllerian hormone Anti-Müllerian hormone (AMH), also known as Müllerian-inhibiting hormone (MIH), is a glycoprotein hormone structurally related to inhibin and activin from the transforming growth factor beta superfamily, whose key roles are in growth differen ...

(AMH; also known as Müllerian-inhibiting substance, "MIF" for "Müllerian-inhibiting factor", "MIH" for "Müllerian-inhibiting hormone", or "APH" for anti-paramesonephric hormone). AMH is a glycoprotein hormone that is secreted by

sustentacular cell A sustentacular cell is a type of cell primarily associated with structural support, they can be found in various tissues. * Sustentacular cells of the olfactory epithelium (also called supporting cells) have been shown to be involved in the phag ...

s (

Sertoli cells Sertoli cells are a type of sustentacular "nurse" cell found in human testes which contribute to the process of spermatogenesis (the production of sperm) as a structural component of the seminiferous tubules. They are activated by follicle-stimula ...

) in males as they begin their morphologic differentiation in response to SRY expression. AMH begins to be secreted around week 8, which in turn causes the paramesonephric ducts to regress very rapidly between the 8th and 10th weeks. However, small paramesonephric ducts can still be identified, and the remnants can be detected in the adult male, located in the

appendix testis The appendix testis (or hydatid of Morgagni) is a vestigial remnant of the Müllerian duct, present on the upper pole of the testis and attached to the tunica vaginalis. It is present about 90% of the time. Clinical significance Torsion The appen ...

, a small cap of tissue associated with the testis. Remnants of the paramesonephric ducts can also be found in the

prostatic utricle The prostatic utricle (Latin for "small pouch of the prostate") is a small indentation in the prostatic urethra, at the apex of the urethral crest, on the seminal colliculus (''verumontanum''), laterally flanked by openings of the ejaculatory duct ...

, an expansion of the prostatic urethra at the center of the

seminal colliculus The seminal colliculus (Latin ''colliculus seminalis''), or verumontanum, of the prostatic urethra is a landmark distal to the entrance of the ejaculatory ducts (on both sides, corresponding vas deferens and seminal vesicle feed into corresponding ...

. AMH receptor-type II (AMHR-II), also known as Misr-II, causes AMH to act indirectly on mesenchymal cells surrounding the paramesonephric ducts rather than acting directly on the epithelium of the duct. This receptor activation induces the ducts to regress. The importance of mesenchyme-to-epithelial signaling is to maintain AMHR-II expression in the mesenchyme. In the absence of the Wnta7a within the duct epithelium as the ducts regress, ductal AMHR-II expression is lost, and residual paramesonephric ducts would be retained in males, throwing off the urogenital system.

Cryptorchidism Cryptorchidism, also known as undescended testis, is the failure of one or both testes to descend into the scrotum. The word is from Greek () 'hidden' and () 'testicle'. It is the most common birth defect of the male genital tract. About 3% of ...

(undescended testis) or

ectopic testis A ectopic testis is a testicle that, although not an undescended testicle, has taken a non-standard path through the body and ended up in an unusual location. The positions of the ectopic testis may be: in the lower part of the abdomen, front of t ...

with

inguinal hernia An inguinal hernia is a hernia (protrusion) of abdominal-cavity contents through the inguinal canal. Symptoms, which may include pain or discomfort especially with or following coughing, exercise, or bowel movements, are absent in about a third ...

s have been identified in human males due to AMH and AMHR-II gene mutations. Studies have revealed another AMH receptor group, AMH receptor-type I (AMHR-I), based on the AMH being a TgfB/Bmp family member. Studies have shown that ALK2, Alk3 (or Bmpr 1a) and Alk6 all serve as AMHR-I receptors. When these receptors are blocked or knocked out in mice within the paramesonephric duct mesenchyme, AMH-induced paramesonephric duct regression is lost.

Function

In females, the paramesonephric ducts give rise to the uterine tubes, uterus, and upper portion of the vagina, while the mesonephric ducts degenerate due to the absence of male androgens. In contrast, the paramesonephric ducts begin to proliferate and differentiate in a cranial-caudal progression to form the aforementioned structures. During this time, the single-layered paramesonephric duct epithelium differentiates into other structures, ranging from the ciliated columnar epithelium in the uterine tube to stratified squamous epithelium in the vagina. The paramesonephric ducts and the mesonephric ducts share a majority of the same mesenchyme due to Hox gene expression. The genes expressed play a critical role in mediating the regional characterization of structures found along the cranial-caudal axis of the female reproductive tract.

Clinical significance

Mutations in AMH

Individuals that are 46, XY and have been tested positive for mutations in their AMH or AMH receptor genes have been known to exhibit features typical of that which are exhibited in

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 typ ...

due to the fact that the paramesonephric ducts fail to regress. When this happens the individuals develop structures that are derived from the paramesonephric duct, and also structures that are derived from the mesonephric duct. A male that has

may have an upper vagina, uterus, and uterine tubes as well as

ductus deferens The vas deferens or ductus deferens is part of the male reproductive system of many vertebrates. The ducts transport sperm from the epididymis to the ejaculatory ducts in anticipation of ejaculation. The vas deferens is a partially coiled tube w ...

along with male external genitalia. The female organs are in the correct anatomical position but the position of the testis varies. 60% to 70% of detected cases, both testes will lie in the normal position for the ovaries; about 20% to 30% of the time, one of the testis will lie within the inguinal hernial sac while in other cases both testes will lie within the same inguinal hernia sac. However whenever an individual exhibits persistent müllerian duct syndrome, the ductus deferens will run along the lateral sides of the uterus.

Paramesonephric duct anomalies

Anomalies that develop within the paramesonephric duct system continue to puzzle and fascinate obstetricians and gynecologists. The paramesonephric ducts play a critical role in the female reproductive tract and differentiate to form the uterine tubes, uterus, superior vagina as well as the uterine cervix. Many types of disorders can occur when this system is disrupted ranging from uterine and vaginal agenesis to the duplication of unwanted cells of the uterus and vagina. Paramesonephric malformations are usually related to abnormalities of the renal and axial skeletal system. Malfunction in the ovaries and age onset abnormalities can also be associated with most paramesonephric ducts. Most often, abnormalities are recognized once the external genitalia is no longer masked and the internal reproductive organ abnormalities become revealed. Due to a very broad range of anomalies it is very difficult to diagnose paramesonephric duct anomalies. Due to improved surgical instruments and technique, women with paramesonephric duct anomalies can have normal sexual relations. Through the use of Vecchietti and Mclndoe procedures women can carry out their sexual activity. On another note, many other surgical advances have tremendously improved fertility chances as well as obstetric outcomes. Assisted reproductive technology makes it possible for some women who have paramesonephric duct anomalies to conceive and give birth to healthy babies.

History

They are named after

Johannes Peter Müller Johannes Peter Müller (14 July 1801 – 28 April 1858) was a German physiologist, comparative anatomy, comparative anatomist, ichthyology, ichthyologist, and herpetology, herpetologist, known not only for his discoveries but also for his ability ...

, a

physiologist Physiology (; ) is the scientific study of functions and mechanisms in a living system. As a sub-discipline of biology, physiology focuses on how organisms, organ systems, individual organs, cells, and biomolecules carry out the chemical a ...

who described these ducts in his text "Bildungsgeschichte der Genitalien" in 1830.

References

External links

*
How the Body Works/Sex Development/Sexual Differentiation/Duct Differentiation
- The Hospital for Sick Children (GTA - Toronto, Ontario, Canada)
Müllerian Duct Anomalies

Müllerian duct
{{Authority control Muellerian duct Vagina