The paramesonephric ducts (or Müllerian ducts) are paired ducts in the embryonic development of the reproductive system of humans and other placental mammals. The ducts run down the lateral sides of the genital ridge, and terminate at the sinus tubercle in the primitive urogenital sinus. In humans, they form in the embryo during the 6th week of gestational age, before sexual differentiation takes place. In the differentiated female, the paramesonephric ducts develop into the reproductive tract, that includes the fallopian tubes (oviducts), uterus, cervix, and the upper part of the vagina.
In the male-determined embryo, the testes produce two hormones responsible for masculinization – anti-Müllerian hormone (AMH), and testosterone. Sertoli cells secrete AMH, during weeks six and seven, which causes the paramesonephric ducts to regress. In week eight Leydig cells secrete testosterone which stimulates the formation of male genitals from the mesonephric ducts.
Each paramesonephric duct is situated just lateral to each mesonephric duct (Wolffian duct). The mesonephric ducts are not completely useless in the female case: they secrete protein Wnt-9b, which is necessary for the elongation of the paramesonephric ducts. Elongation also happens through the active migration of the paramesonephric epithelium, which happens through a phosphoinositide 3-kinase pathway.
Development
thumb|left|Schematic of [[sexual differentiation of the gonads]]
The female reproductive system develops from two embryological segments: the urogenital sinus and the paramesonephric ducts. The two are conjoined at the sinus tubercle. Paramesonephric ducts are present on the embryo of both sexes. Only in females do they develop into reproductive organs. They degenerate in males whereas the adjoining mesonephric ducts 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.
Initial formation
During the development of the reproductive system, the paramesonephric ducts are formed just lateral to the mesonephric ducts (formed earlier) in both female and male embryos 6 weeks after fertilization. A ribbon of thickened coelomic epithelium is selected by PAX2, and in turn the FGFs, and in turn LHX1, to become the Müllerian surface epithelium (MSE). During this time, primordial germ cells migrate from the yolk sac to the genital ridge, a region of mesenchyme running parallel with, and derived from, the mesonephros. The Müllerian duct mesenchyme (MDM) is formed from the MSE and possibly the mesonephros; WNT4 expression is required for this process.
{| class="wikitable"
| Male embryogenesis || The developing testes produce AMH causing regression of the paramesonephric ducts. || Disturbances can lead to persistent Müllerian duct syndrome. || The ducts disappear except for the vestigial vagina masculina and the appendix testis.
|-
| Female embryogenesis || The absence of AMH results in the development of the paramesonephric ducts into the uterine tubes, uterus, and the upper 2/3 of the vagina. || Disturbance in the development may result in uterine absence (Müllerian agenesis) or uterine malformations. || The ducts develop into the upper vagina, uterus, and uterine tubes.
|}
AMH is a glycoprotein hormone that is secreted by Sertoli cells (a type of sustentacular cell) 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, a small cap of tissue associated with the testis. Remnants of the paramesonephric ducts can also be found in the prostatic utricle, an expansion of the prostatic urethra at the center of the seminal colliculus.
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 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 persistent Müllerian duct syndrome may have an upper vagina, uterus, and uterine tubes as well as ductus deferens 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.
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.