PART One
General Gynecology
The reproductive organs in the female (as also in the male) consist of gonads, external genitalia and an internal duct system between the two. Since these three components originate from different primordia in close association with the urinary system and the hindgut, the embryological development is complex and developmental abnormalities are often interrelated.1
INDIFFERENT EMBRYO
The hindgut appears about the twentieth postovulatory day. The intermediate mesoderm develops adjacent to the midline dorsal mesentery of the gut, extending through the length of the body cavity (celom). A part of this intermediate cell mass medial to the mesonephros (primitive kidney), proliferates to form the gonadal ridges. These bilateral thickenings being recognizable in the 4 to 5 mm embryo (Fig. 1.1).
Indifferent Gonad
Primordial germ cells that are subsequently capable of meiosis, separate out from the pool of somatic cells that are capable only of mitosis. These germ cells are present in the allantoic diverticulum and the adjacent parts of the yolk sac in 17 to 20 day embryos. From here they migrate through the dorsal mesentery of the hindgut, reaching the gonadal ridge in the human embryo at 35 days (Fig. 1.1). The cause of this migration of the germ cells is yet unknown.
The area to which the germ cells migrate is referred to as the indifferent gonad until gonadal sex is established. At 35 days the indifferent gonad is formed by the primordial germ cells, cells from the overlying coelomic epithelium and the cells of the adjacent mesonephros. The germ cells now undergo rapid mitotic proliferation and are enclosed by extensions of the coelomic epithelium (sex cords) and the mesonephric ducts.
Mesonephric (Wolffian) Ducts
In 1759 Caspar Wolff studying the embryology of the chick described a symmetrical pair of paravertebral swellings as the precursors of the kidneys. The term Wolffian has been subsequently used to describe the mesonephric ducts and vesicles.
The first indication of the urinary system appears at 21 days when the mesonephric vesicles develop. These are associated with a solid cord of cells in the intermediate mesoderm, that acquire a lumen at 26 days, forming the mesonephric ducts. Skirting the hind-gut the bilateral mesonephric ducts open into the urogenital sinus at 28 days (Fig. 1.2). At 32 days, the caudal end of each mesonephric duct gives rise to the ureteric bud and is incorporated into the posterior wall of the urogenital sinus, subsequently forming the trigone of the bladder and the posterior wall of the urethra. The mesonephros attains maximum size and function at 42 days, the metanephros taking over excretory function after 50 days.
Paramesonephric (Müllerian) Ducts
In 1830 Johannes Müller described a cord on the outer aspect of the Wolffian body, but thinner than the Wolffian cord. These müllerian cords now referred to as the paramesonephric ducts, appear at about 40 days.
Each paramesonephric duct (müllerian duct) begins as a thickening and an invagination of the coelomic epithelium, on the lateral aspect of the intermediate mesoderm. It extends caudally as a solid rod of cells and is associated with and initially lateral to the mesonephric duct. The ducts are interdependent; the paramesonephric duct will not develop if the mesonephric duct is absent.2
As the paramesonephric cord of cells continues its descent, a lumen appears in its cranial portion in continuity with the intraembryonic body cavity. The lumen extends caudally, as the ducts pass ventral to the mesonephric ducts, come in close association with each other and reach the posterior aspect of the urogenital sinus (Fig. 1.2).
Urogenital Sinus
The hindgut and the cloaca are established by a process of flexion, as that part of the yolk sac enclosed within the tailfold of the embryo. At an early stage the hindgut and the urogenital ducts open into a common cloaca (Fig. 1.3A). The mesoderm between the allantoic diverticulum and the hindgut then extends caudally in line with the curvature of the tail fold as the urorectal septum. The urorectal septum reaches fuses with the cloacal membrane at 30 to 32 days, completely dividing the cloaca into the ventral urogenital sinus and the dorsal rectum (Fig. 1.3B).3
Figures 1.3A and B: (A) The hindgut and urogenital ducts opening into the cloaca, (B) Fusion of the urorectal septum with the cloacal membrance
The functioning mesonephros now produces an increase in the pressure in the closed urogenital sinus, rupturing the ventral part of the cloacal membrane and allowing the urogenital sinus to communicate with the amniotic cavity.
FEMALE GONADAL DIFFERENTIATION
Male and female embryos are morphologically indistinguishable till 42 days when the transformation of the indifferent gonad into an embryonic testis begins to occur. The Leydig cells in the testes produce testosterone from 56 days onwards, while the Sertoli cells synthesise the antimüllerian hormone. The secretion of the antimüllerian hormone begins soon after testicular differentiation and continues into the prenatal period, though it is functional only for a short period during early gestation.
The transformation of the indifferent gonad into an embryonic ovary occurs gradually between 45 and 55 days.
Development of the Ovary
A gonad with the germ cells in meiosis is always an ovary since meiotic division does not occur in the testes until puberty. Meiosis I begins in the ovary in intrauterine life, only to be completed at ovulation some 15–45 years later. Meiosis II occurs at fertilization. During the early fetal stage, the ovaries contain five million germ cells, that along with the sex cords from the coelomic epithelium, remain in the superficial part of the ovary, the future cortex. The cords lose contact with the surface, forming small groups of cells each with a germ cell, a primitive follicle.
Meanwhile the ovary descends extraperitoneally, its descent controlled by the suspensory ligament that connects it to its site of origin on the genital ridge, and the gubernaculum. The gubernaculum is the inferior continuation of the genital mesentery, that becomes attached to the uterine cornu forming the proximal ovarian ligament and continues as the distal round ligament passing through the inguinal canal and ending in the labium majus3(Fig. 1.4).
The total number of germ cells in the ovary decline to about two million at birth and only 4,00,000 oocytes at the onset of puberty. Of these 400 will be ovulated during reproductive life, the remaining 99.9% undergoing atresia.
FEMALE GENITAL DUCT DIFFERENTIATION
At the end of the embryonic period the fetus has gonads recognizable as either testes or ovaries, but possesses both the mesonephric ducts and the paramesonephric ducts. The subsequent differentiation of the ducts is governed by fetal testicular hormones. In the male fetus müllerian duct regression begins under the influence of the antimüllerian hormone at 50 to 60 days,4 while the mesonephric ducts are stabilized under the influence of testosterone between 56 and 70 days. In contrast, the absence of testicular hormones in the female fetus allows the stabilization of the müllerian ducts and a regression of the mesonephric ducts to take place.
The basic sequence of change from the bipotential state is directed by chromosomal sex determined gonad formation, which then favors the development of male or female duct systems and external genitalia. In final analysis this depends on endocrine effects and not chromosomal sex.5
The development of the female genitourinary tract is nearly complete at the end of the first trimester, with some changes such as the final canalization of the vagina and repositioning of the gonads taking place later.
Development of the Uterus
The paired müllerian ducts meet in the midline, fusing within the urorectal septum at the end of the embryonic period. The müllerian ducts fuse, forming the uterus around 63 days, the median septum being completely reabsorbed by 80 days, forming a single uterovaginal canal. While the complete failure of fusion between the ducts results in a didelphic uterus, a partial failure results in an arcuate or a bicornuate uterus and a failure of septal resorption results in variants ranging from a subseptate to a septate uterus.5,6
In the fetus the cervix forms two-thirds of the uterus. The corpus differentiates into the serosal, muscular and mucosal layers at 19 weeks, the endometrial glands forming a week later. The uterus at birth and during childhood is devoid of flexion and version, these characteristics developing at puberty.
Development of the Fallopian Tubes
The separated upper part of each müllerian duct retains its identity to from the fallopian tube, the open cranial segment of the duct developing fimbriae. The transverse lie of the tubes is established by the descent of the ovaries.
Development of the Vagina
There is general agreement that the vagina originates as a composite formed partly from the müllerian ducts and partly from the urogenital sinus.
The müllerian tubercle is the point of contact between the müllerian ducts and the urogential sinus. The tip of the fused müllerian ducts proliferates to form the solid vaginal cord that elongates to meet bilateral evaginations from the urogenital sinus (sinovaginal bulbs). The sinovaginal bulbs fuse with the vaginal cord to form the vaginal plate. Canalization of the vaginal cord occurs, followed by epithelialization, mostly with cells from the urogenital sinus.
According to current hypothesis only the upper third of the vagina is formed from the müllerian ducts, with the lower vagina developing from the vaginal plate of the urogenital sinus below.
Development of the External Genitalia
The external genitalia develop in the area bound by the body stalk above and the tail below, the sex of the external genitalia being unrecognizable till the twelfth week.
Five swellings appear around the urogenital sinus on the surface of the embryo. The genital tubercle is the midline swelling at the cephalic end formed by the fourth week. The paired genital or labial swellings develop on either side of the urogenital membrane, with the paired genital folds appearing medial to them (Fig. 1.5A). The genital tubercle will become the clitoris, the genital swellings developing into the labia majora and the genital folds into the labia minora (Fig. 1.5B).5
Figures 1.5A and B: (A) The indifferent external genitalia, (B) Feminization of the external genitalia
The Bartholin's glands and the Skene's glands develop from outgrowths from the urogenital sinus. The urorectal septum will finally form the perineal body.
REFERENCES
- Boyd ME, Daniels E. Development of the female genital tract and external genitalia. In Gidwani G, Falcone T (Eds): Congenital Malformations of the Female Genital Tract. Lippincott Williams & Wilkins: Philadelphia 1999; 1–20.
- Lytle W. The deep inguinal ring: Development, function and repair. Br J Surg 1970; 57: 531–37.
- Terruhn V. A study of impression moulds of the genital tract of female fetuses. Arch Gynecol 1980; 229: 207–17.
- Josso N, Picard JY, Tran D. The antimüllerian hormone. Recent Prog Horm Res 1977; 37: 117–20.
- Duncan S. Embryology of the female genital tract: Its genetic defects and congenital anomalies. In Shaw R, Soutter W, Stanton S (Eds): Gynecology. Churchill Livingstone, New York: 1997, 1–22.
- Rock J, Schlaff W. The obstetric consequences of uterovaginal anomalies. Fertil Steril 1985; 43: 681–92.