The Development of the Human Female Reproductive Tract. Part 1: Uterine Tube and Uterus.

In 9-weeks prefetuses, urogenital complexes are located lower than in prefetuses of previous age groups. In the vertical sections of the urogenital cords, the paramesonephric ducts diff erentiate into the uterine tubes. Above the entrance to the pelvis, the urogenital cords pass obliquely in the vertical direction, at the level of which the paramesonephric ducts are connected, on both sides of which the mesonephric ducts are located. The primary kidneys are completely reduced in their upper two-thirds, the reduction of mesonephric cells in the lateral areas of the lower third of the kidneys begins. The caudal divisions of the paramesonephric ducts touch dorsally to the wall of the urogenital sinus, while the lower ends of the mesonephric ducts are in the thickness of the wall. The urogenital cords (mesonephric and paramesonephric ducts) protrude above the upper ends of the primary kidneys and below the permanent kidneys. The mesonephric and paramesonephric ducts are clearly demarcated by a layer of loosely spaced mesenchymal cells.In 10-weeks prefetuses, due to the connection of the lower vertical parts of the paramesonephric ducts, a common uterine- vaginal canal is formed, lined with pseudolayered epithelium. Mesonephric ducts retain their lumen in fragments.In 11-weeks prefetuses, the upper vertical sections of the urogenital cords, in connection with the reduction of the mesonephric ducts, contain mainly paramesonephric ducts, which are separated from each other by a loose layer of the mesenchyme. From these sections of paramesonephric ducts uterine tubes are formed. Oblique (middle) sections of the paramesonephric ducts with further development are transformed into intrauterine parts of the uterine tubes. The lower caudal sections of the paramesonephric ducts are transformed into the uterus and the upper two-thirds of the vagina.In 12-weeks prefetuses, the primary kidneys are almost completely reduced. Only single mesonephric tubules within their caudal area are determined. In parallel, there are intense processes of formation of internal female reproductive organs. The cranial ends of the uterine tubes expand, acquiring a funnel- shaped shape. The outer border of the infundibulum of the tube reminds a zigzag line, which is evidence of the beginning of the formation of the fi mbria of the uterine tube. The lumens of the mesonephric ducts are reduced to 6±0.1 μm, and in some parts of their walls are in contact with each other. Transformation of paramesonephric ducts into their derivatives (uterine tubes, uterus, upper part of the vagina) is accompanied by corresponding histological changes of their walls.

The mesonephric (Wolffian) and paramesonephric (Müllerian) ducts of golden hamsters express different intermediate-filament proteins during development

The paramesonephric (Müllerian) duct was first observed in the vicinity of the mesonephric (Wolffian) duct in 30-day-old swine fetuses of both sexes at the level close to the gonad. The paramesonephric duct extended caudally in parallel with the mesonephric duct on day 35 of gestation. By day 40 the paramesonephric duct reached the urogenital sinus. At this stage, the paramesonephric duct began to degenerate in the male, while it continued to develop in the female. This suggests that an anti-Müllerian duct hormone (AMH) is produced before day 40 of gestation. By day 45 of gestation, the mesonephric duct began to decrease in diameter and was accompanied with the involution of the mesonephros in both sexes. By day 60, the male and female mesonephric ducts reduced in their diameter by 70%. Thereafter, the female mesonephric ducts disappeared, while the male ducts developed again. The sex differences was first observed on day 35 in the differentiation of the external genitalia when a small circular urogenital orifice and the anogenital raphe appeared at the sites caudal to the genital tubercle in the male. Such structures were not present in the female. These results suggest that the fetal pig testis is activated to secrete androgen before day 35 of gestation.

The reproductive tract in mammals emerges from two ductal systems during embryogenesis: Wolffian ducts (WDs) and Mullerian ducts (MDs). Most of the female reproductive tract (FRT) including the oviducts, uterine horn and cervix, originate from MDs. It is widely accepted that the formation of MDs depends on the preformed WDs within the urogenital primordia. Here, we found that the WD mesenchyme under the regulation of Hedgehog (Hh) signaling is closely related to the developmental processes of the FRT during embryonic and postnatal periods. Deficiency of Sonic hedgehog (Shh), the only Hh ligand expressed exclusively in WDs, prevents the MD mesenchyme from affecting uterine growth along the radial axis. The in vivo cell tracking approach revealed that after WD regression, distinct cells responding to WD-derived Hh signal continue to exist in the developing FRT and gradually contribute to the formation of various tissues such as smooth muscle, endometrial stroma and vascular vessel, in the mouse uterus. Our study thus provides a novel developmental mechanism of FRT relying on WD.

An ultrastructural study of the developing urogenital tract in early human fetuses

On day 13 of gestation in Mongolian gerbil fetuses, the mesonephric (Wolffian) duct was already visible. On day 14, the anlage of the paramesonephric (Müllerian) duct was first observed close to the mesonephric duct in both sexes at the cranial part of the mesonephros. Thereafter, the paramesonephric duct grew caudally in parallel with the mesonephric duct. On day 19, the duct reached the urogenital sinus. At this stage, the anogenital distance was significantly longer in male than in female. Also in male, the mesonephric duct was increased and the paramesonephric duct was decreased in diameter compared with those in female. These suggest that both testosterone and anti-Müllerian hormone are produced in fetal Mongolian gerbils at least before day 19 of gestation.

Epithelial and mesenchymal cell differentiation in the fetal rat genital ducts: Changes in the expression of cytokeratin and vimentin type of intermediate filaments and desmosomal plaque proteins

Mullerian inhibiting substance is a testicular hormone that causes involution of the mullerian ducts in male fetuses during normal genital tract differentiation (reviewed in Josso et al., 1977; Donahoe et al., 1982, 1987; Josso and Picard, 1986; Cate et al., 1990). In early fetal development, the gonads are bipotential and the mullerian and wolffian ducts are both present in the urogenital ridge: the former are the anlagen of the uterus, fallopian tubes, and the upper third of the vagina, and the latter are the embryologic precursors of the epididymis, vas deferens, and seminal vesicles. During normal female reproductive tract development, the mullerian ducts develop spontaneously, and the wolffian ducts atrophy in the absence of testosterone. In males, the wolffian ducts are stimulated to differentiate by testosterone, and the mullerian ducts regress under the influence of another hormone secreted by Sertoli cells. This hormone, termed mullerian inhibiting substance (MIS), has been identified as a 140 kDa glycoprotein composed of two identical 70 kDa subunits. The MIS gene, which has been cloned and sequenced (Cate et al., 1986a), is a member of the transforming growth factor-/3 (TGF-/3) family of proteins that are all involved in growth and differentiation (Sporn et al., 1987; Massague, 1990). The purification and characterization of MIS, including its gene regulation, posttranslational modification, and mechanism of action are reviewed in this chapter. Current and potential areas of MIS re-search, including newly discovered functions of the hormone, are discussed.

The urogenital ridge of the developing mammalian embryo is a complex structure in which the Wolffian and Mullerian ducts, each comprised of luminal epithelium surrounded by mesenchyme, develop side by side. As the maturing gonad begins to declare its genetic sex as either an ovary or testis, significant changes occur in the ducts contained within the urogenital ridge. If the gonad is an ovary the Wolffian duct, which develops into the epididymis, vas deferens, and seminal vesicles of the male, begins to atrophy while the Mullerian ducts expand. Conversely, testicular development coincides with the regression of the Mullerian ducts, the precursor of the ovarian coelomic epithelium, Fallopian tubes, uterus, cervix, and upper third of the vagina. As expected in this case, the Wolffian duct continues to enlarge.

Epithelio-mesenchymal interface and fibronectin in the differentiation of the rat mesonephric and paramesonephric ducts

Developmental changes in interstitial collagens of fetal rat genital ducts

In my presentation, I review the sexual differentiation from the genetic sex until the appearance of the external genitalia and the developmental anomalies to use an animated cartoon. The first critical stage of sexual differentiation occurs at the moment of fertilization, when the genetic sex of the zygote is determined by the nature of the sex chromosome contributed by the sperm. Although an XY zygote is destined to become a male, no distinctive differences between the early development of male and female embryos have been noted. This is accomplished after migration of the primordial germ cell into the early gonad. Because of the early commonality of genital structures, anomalies are the result of abnormal retention or loss of appropriate genital structures. Therefore, most genital anomalies are some form of intersex. During the early differentiation of the gonads, while the mesonephros is still the dominant excretory organ, the gonads arise as ridge like thickenings (gonadal ridge) on its ventromedial face. Differentiation of the indifferent gonads into ovaries or testes occurs after the arrival of the primordial germ cells. The primordial germ cells arise from the endodermal cells of the yolk. The principal function of the Y chromosome is to direct the differentiation of the presented indifferent gonad into a testis from the sixth week, while two X chromosome are presented the ovaries start to develop, from the 12th week. The next and most obvious phase in sexual differentiation of the embryo is the differentiation of the somatic sex. The early embryo develops a dual set of potential genital ducts, one is the original mesonephric (Wolff ) ducts, which persists after degeneration of the mesonephros as an excretory organ, and the another is newly formed pair of ducts called the paramesonephric (Müllerian) ducts. Under the influence of testosterone secreted by the testes, the mesonephric ducts develop into the duct system through which the spermatozoa are conveyed from the testes to the urethra. The potentially female paramesonephric ducts regress under the influence of another product of the embryonic testes, the Müllerian inhibitory factor, a glycoprotein secreted by the Sertoli cells. In genetically female embryos, neither testosterone nor Müllerian inhibitory factor are secreted by the gonads. In the absence of testosterone the mesonephric ducts regress and lack of Müllerian inhibitory factor permits the paramesonephric ducts to develop into oviducts, the uterus and part of the vagina. The next stage is the development of the external genitalia. In very young embryos, a vaguely outlined elevation known as the genital eminence can be seen in the midline, just cephalic to the proctodeal depression. This is soon differentiated into a central prominence (genital tubercle) closely flanked by a pair of folds (genital folds) extending toward the proctodeum. Somewhat farther to either side are rounded elevation known as the genital swellings. From this common starting point the external genitalia of both sex differentiate. If the individual is to develop into a male the genital tubercle, under the influence of dihydrotestosterone, becomes greatly elongated to form the penis and the genital swellings become enlarged to form the scrotal pouches. During the growth of the penis a groove develops along the entire length of its caudal face and is continuous with the slit‐like opening of the urogenital sinus. This groove later becomes closed over by a ventral fusion of the genital folds, establishing the penile portion of the urethra. The portion of the urogenital sinus between the neck of the bladder and the original opening of the urogenital sinus becomes the prostetic urethra. In the female, the genital tubercle becomes the clitoris, the genital folds become the labia minora, and the genital swellings become the labia majora. The urethra in the female is derived from the urogenital sinus, being homologous with the prostatic portion of the male urethra.

Molecular analysis of WNT4 gene in four adolescent girls with mullerian duct abnormality and hyperandrogenism (atypical Mayer-Rokitansky-Küster-Hauser syndrome)

Basement membrane in differentiating mesonephric and paramesonephric ducts of male and female rat fetuses

The female reproductive tract develops from the mullerian ducts. Mullerian duct development will not proceed in the absence of the mesonephric duct (Freedman and Shapiro, 1997; Gruenwald, 1943). The mullerian ducts adhere to each other just before they project into the dorsal wall of the urogenital sinus (UGS) causing an elevation termed the sinus tubercle. When the fused tips contact the sinus tubercle, the ducts fuse cranially, forming a tube with a single lumen called the uterovaginal primordium or canal (O’Rahilly, 1977). This tube will ultimately become the superior aspect of the vagina and uterus (Larsen, 1993). The cranial portion of the mullerian ducts which are unfused, develop into the fallopian tubes (George and Wilson, 1988). The original coelomic epithelial ostium remains as the abdominal opening of the fallopian tube. A septum initially divides the uterus into two cavities. This septum between the fused ducts disappears after 9 weeks, forming a single uterine cavity. The mesonephric ducts regress one week later, leaving a remnant in the female which is termed Gartner’s duct (Arey, 1974). Muscularization of the uterus is completed by 17 weeks gestation and forms from the mesenchyme surrounding the mullerian ducts.KeywordsAndrogen ReceptorAcid PhosphataseCongenital Adrenal HyperplasiaExternal GenitaliaAndrogen Receptor ExpressionThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.