DEVELOPMENT OF EXTERNAL GENITAL ORGANS
The external genital organs start developing almost simultaneously with the development of the internal genital organs. The site of origin is from the urogenital sinus (Fig. 3.1). The endodermal cloaca is divided by a coronally oriented vertical partition, known as urorectal septum. The urorectal septum contains a pair of paramesonephric ducts close to the midline and a pair of mesonephric ducts laterally. The dorsal part of the endodermal cloaca, thus formed, differentiates to form the rectum and anal canal. The ventral portion, known as urogenital sinus, differentiates into three parts (Fig. 3.4).
a. Upper vesicourethral part forms the mucous membrane of the bladder except the trigonal area. It also contributes to the major part of female urethra.
b. Middle pelvic part of urogenital sinus: It receives the united caudal end of the two para-mesonephric ducts in the midline. Derivatives of this part differentiates into the epithelium of the vagina, Bartholin’s gland, and the hymen.
c. The lower phallic part of the urogenital sinus:
It is lined by the bilaminar urogenital membrane (see below). It contributes to vestibule of vagina.
The site of fusion between the urorectal septum and the cloacal membrane is the primitive perineal body.
The part of the cloacal membrane in front of the primitive perineal body is called urogenital membrane and the part behind is called anal membrane. When the urogenital membrane ruptures, the genital folds do not reunite in female (e.f. male). They persist as labia minora. The perineal cleft persists as vestibule, into which the urethra and the vagina open. The ectodermal swelling, one on either side and lateral to the genital fold is called labioscrotal swelling. Eventually they form the labia majora.
The genital folds meet at the cephalic end of the cloacal membrane to form an elevation. This elevation is known as genital tubercle, which ultimately differentiates into the clitoris.
Fig. 3.1: Diagrammatic representation showing differentiation of the female external genitalia
Fig. 3.2: Diagrammatic representation showing development of male reproductive systems from the primitive genital ducts. Vestigial structures are also shown (see p. 39)
Development up to this stage is the same in the male and the female (50 mm CR length, 10 weeks).
If the gonads become ovaries, the external genitalia will attain the female characteristics (Table 3.1).
♦ Clitoris is developed from the genital tubercle.
♦ Labia minora are developed from the genital folds.
♦ Labia majora are developed from the genital swellings.
♦ The Bartholin's glands are developed as outgrowths from the caudal part of the urogenital sinus and correspond to the bulbourethral glands of male.
♦ The vestibule: The inferior portion of the pelvic part (Fig. 3.4D) and whole of the phallic part of the urogenital sinus expand to form the vestibule of the vagina (at about 5th month). It receives the openings of urethra, the vagina and Bartholin’s ducts (Fig. 3.1).
DEVELOPMENT OF INTERNAL GENITAL ORGANS
■ Fallopian tubes ■ Uterus
■ Broad ligaments ■ Vagina
The major part of the female genital tract develops from the Müllerian ducts. The duct forms one on each side as an ingrowth of coelomic epithelium in the lateral aspect of mesonephros at about 5-6 weeks (10 mm CR length). The ingrowth forms a groove and then a tube, which goes beneath the surface. While it grows downwards, it has developed three parts—(1) cranial vertical, (2) middle horizontal, and (3) caudal vertical after crossing the Wolffian duct anteriorly. In the absence of androgen (testosterone) and anti-Müllerian hormone (AMH), as in a normal female, there is further growth and development of the Müllerian duct system with regression of the Wolffian ducts (Figs 3.3 and 3.6).
Fig. 3.3: Diagrammatic representation showing development of female reproductive systems from the primitive genital ducts. Vestigial structures are also shown. (A) Female fetus at 12 weeks; (B) Newborn female
FALLOPIAN TUBES
Fallopian tube is developed from upper vertical part and the adjoining horizontal part of the Müllerian duct. The coelomic opening of the duct becomes the abdominal ostium.
UTERUS
Uterus is developed by the fusion of the intermediate horizontal and the adjoining vertical part of the Müllerian ducts, which begins at 7-8 weeks (22 mm CR length) and completes by 12th week. Cervix is developed from the fused lower vertical parts of the two paramesonephric ducts. The cervix is differentiated from the corpus by 10th week. The intervening septum disappears during the 5th month of intrauterine life. The lining epithelium and the glands of the uterus and cervix are developed from the coelomic epithelium. Myometrium and endometrial stroma are developed from the mesoderm of the paramesonephric ducts.
BROAD LIGAMENT
When the Mullerian ducts approach each other in the midline, a broad transverse fold is established. It extends from the lateral side of the fused Müllerian ducts up to the lateral pelvic walls, which is named as Broad ligament. All the vestigial remnants of mesonephric tubules, i.e. epoophoron (situated above the ovary), paroophoron (between ovary and uterus) and the duct, remnant as Gartner’s duct are found in the broad ligament in the mesosalpinx (Fig. 3.3).
Kobelt’s tubules on the outer set are said to be of pronephric origin (Fig. 1.12).
VAGINA
Development of vagina is composite, partly from the Müllerian (paramesonephric) ducts and partly from the urogenital sinus.
The paramesonephric ducts develop at about sixth week, as an invagination of coelomic epithelium lateral to each mesonephric (Wolffian) duct. Each paramesonephric duct passes ventral to the corresponding mesonephric duct and then meets its counterpart from the opposite side in the midline (Fig. 3.4). The lower vertical parts of the two paramesonephric (Mullerian) ducts pass caudal wards in the urorectal septum and meet each other. Around 9th week, the solid caudal tip of the fused vertical parts of the Mullerian ducts project blindly into the dorsal wall of the urogenital sinus as Müllerian tubercles (Fig. 3.4A).
The paramesonephric ducts shortly undergo fusion with each other and the partition between them disappears. The united lower vertical parts form the uterovaginal canal and the fused Mullerian tubercles form the Müllerian eminence. The unfused cranial part of each paramesonephric duct forms the uterine tube and the distal open end forms the abdominal ostium.
Fig. 3.4: Schematic representation of the development of genitourinary system (internal genital organs)
(A) Formation of Müllerian tubercle; (B) Earliest development of vaginal plate and mesonephric duct; (C & D) Further development of the paramesonephric ducts and urorectal septum, permanent (metanephric) kidney and urogenital sinus: (a) vesical (b) pelvic and (c) phallic parts, urinary bladder and anorectal canal (B)
The endodermal cells from the dorsal wall of the urogenital sinus proliferate and form the sinovaginal bulb (Fig. 3.4B). These endodermal cells further proliferate and extend cranially into the central axis to form a solid plate, called vaginal plate. This vaginal plate elongates thereby increasing the distance between the urogenital sinus (below) at the cervix (above).
At about 20 weeks the vaginal plate undergoes canalization with the disintegration of the central cells. The upper end of the canal forms the vaginal fornices and communicates with the cervical canal and uterine cavity.
Central cells of the Müllerian eminence disintegrate, so that the vaginal canal now opens into the urogenital sinus (Fig. 3.4C). The tissue at the periphery persists as hymen. It is lined by sinus epithelium (endodermal origin) on either side with a thin mesoderm in between. Thus, whole of the vagina is lined by endoderm of the urogenital sinus and the muscle in the wall is derived from the mesoderm of the Mullerian ducts.
Finally, the urogenital membrane ruptures and the genital folds persist as the labia minora.
Eventually, the vaginal segment grows and is extended between the paramesonephric derived cervix at the top and the sinus derived vestibule at the bottom.
DEVELOPMENT OF THE OVARY
♦ Site
♦ Sources
♦ Indifferent or primitive gonad
♦ Definitive gonad
♦ Descent of the ovary
Fig. 3.5: Differentiation of the indifferent gonads into ovary and testis with migration of the germ cells into the genital ridge (TDF = Testicular Determining Factor)
Site
The ovary is developed on either side from the genital or gonadal ridge. This ridge is formed in a four-week embryo between the dorsal mesentery (medially) and the mesonephric ridge (laterally) by the multiplication of the coelomic epithelium along with condensation of the underlying mesenchyme (Fig. 3.5).
Sources
The cortex and the covering epithelium are developed from the coelomic epithelium and the medulla from the mesenchyme. The germ cells are of endodermal origin. They migrate from the yolk sac to the genital ridge along the dorsal mesentery by ameboid movement between 20 and 30 days. The germ cells undergo a number of rapid mitotic divisions and differentiate into oogonia. The number of oogonia reaches its maximum at 20th week numbering about 7 million. The mitotic division gradually ceases and the majority enter into the prophase of the first meiotic division and are called primary oocytes. These are surrounded by flat cells (granulosa cells) and are called primordial follicles. At birth, there is no more mitotic division and all the oogonia are replaced by primary oocytes. The estimated number at birth is about 2 million (details p. 82).
Indifferent or Primitive Gonad
Initially, the gonads do not acquire male or female morphological characteristics until the seventh week of development. Around the time of arrival of germ cells, the coelomic epithelium of the genital ridge proliferates. The irregular cords of cells (primitive sex cords) invaginate the underlying mesenchyme. These cords of cells surround the primordial germ cells and still have connection with the surface epithelium. It is difficult at this stage to differentiate between an ovary and testis.
Fig. 3.6: Schematic representation of the development of the reproductive system in the male and female
TABLE 3.1 MALE AND FEMALE DERIVATIVES OF EMBRYONIC UROGENITAL STRUCTURES
|
Embryonic structure |
Derivatives |
|
|
Male (Fig. 3.2) |
Female (Fig. 3.3) |
|
|
Labioscrotal swelling |
Scrotum |
Labia majora |
|
Urogenital folds |
Ventral aspect of penis |
Labia minora |
|
Genital tubercle |
Penis |
Clitoris |
|
Urogenital sinus |
Urinary bladder Urethra except navicular fossa Prostate gland Prostatic utricle Bulbourethral glands |
Urinary bladder, urethra Urethral and paraurethral glands Vagina Bartholin’s glands |
|
Paramesonephric duct |
Appendix of testes |
Hydatid of Morgagni, uterus, cervix fallopian tubes, vagina (muscular wall) |
|
Mesonephric duct |
Ductus epididymis Ductus differens and seminal vesicles |
Duct of epoophoron Gartner’s duct |
|
Mesonephric tubules |
Ductuli efferentes Paradidymis |
Epoophoron Paroophoron |
|
Undifferentiated gonad Cortex Medulla |
Testis Seminiferous tubules Rete testis |
Ovary Ovarian follicles Rete ovarii |
|
Gubernaculum |
Gubernaculum testis |
Ovarian ligament Round ligament |
|
Mullerian tubercle |
Seminal colliculus |
Hymen |
Definitive Gonad
In a XX individual, without the active influence of Y chromosome, the bipotential gonad develops into an ovary about two weeks later than testicular development. SRY gene located on the short arm of Y chromosome directly controls the differentiation of testis from the bipotential gonad. Apart from SRY, autosomal genes are also essential for differentiation of the gonads. Absence of SRY gene leads to female sex differentiation (Fig. 3.6).
Genetic control is of prime importance for differentiation of bipotential gonad. Genes that regulate the process are: Wilms’ tumor gene (WTI), FTZI and SRY.
Second gene involved in development of testis is SOX9 and anti-Müllerian hormone (produced by Sertoli cells). DAXI gene expression is involved in ovarian differentiation. DAXI antagonizes the action of SRY gene.
The surface becomes thicker and continues to proliferate extensively. It sends down secondary cords of cells into the mesenchyme (cortical cords), but unlike testis, maintains connection with the surface epithelium. In the fourth month, these cords split into clusters of cells, which surround the germ cells.
The germ cells will be the future oogonia and the epithelial cells will be the future granulosa cells. From 20th week, the oocytes that are not surrounded by the granulosa cell envelope, are destroyed. The stromal mesenchymal cells also surround the follicular structure to form the future theca cells. Thus, a basic unit of a follicle is completed. By 28th week, number of these follicles are exposed to maternal gonadotropin and undergo various degrees of maturation (little short of antrum formation) and atresia.
Descent of the Ovary
The cranial part of the genital ridge becomes the infundibulopelvic ligament (Fig. 3.3). From the lower pole of the ovary, genital ligament (gubernaculum) is formed, which is attached to the genital swelling (labial). Gubernaculum is a fibromuscular band. The genital ligament gets an intermediate attachment as it comes close to Müllerian ducts (angle of the developing uterus). The part between the ovary and the Müllerian attachment is the ovarian ligament and the part between the cornu of the uterus to the end is the round ligament. The ovaries descend during the seventh to ninth months, and at birth, they are situated at the pelvic brim.
KEY POINTS
> The external genital organs start developing almost simultaneously with the development of the internal genital organs.
> Clitoris is developed from the genital tubercle, labia minora from the genital folds and labia majora from the genital swellings.
> Bartholin's glands are developed from the caudal part of the urogenital sinus.
> Major part of the vagina is developed from urogenital sinus.
> SRY (sex-determining region of the Y chromosome) gene directly controls the testicular differentiation from the bipotential gonad. SRY gene encodes the testicular determining factor (TDF), which induces the differentiation. Testicular development is an active event whereas ovarian development is a default pathway due to absent SRY gene.
> An individual with absent SRY gene, though the chromosomal complement is 46, XY, the gonadoductal development is towards female (XY gonadal dysgenesis).
> The ovary is developed from the gonadal ridge. The cortex and the covering epithelium are developed from the coelomic epithelium and the medulla from the mesenchyme. The germ cells are endodermal in origin and migrate from the yolk sac to the genital ridge. The number of oogonia reaches its maximum at 20th week numbering about 7 million. The estimated number at birth is about 2 million.
> The bipotential gonad develops into an ovary about two weeks later than the testicular development.
> The cranial end of the genital ridge becomes the infundibulopelvic ligament.
> The ovary is developed from the middle part of the genital ridge.
> The part of the gubernaculum (genital ligament) between the lower pole of the ovary and the Müllerian attachment is the ovarian ligament. The part between the cornu of the uterus (Müllerian attachment) to the end (external genitalia) is the round ligament.
> The ovaries descend during seventh to ninth months, and at birth, they are situated at the pelvic brim.
> The paramesonephric duct in female differentiates into fallopian tube, uterus and cervix. The mesonephric duct in male gives rise to epididymis, vas deferens and seminal vesicles. The sinovaginal bulbs, which grow out from the posterior aspect of the urogenital sinus, differentiates into vagina. The genital tubercle differentiates into clitoris (female) or penis (male). The urinary bladder develops from the urogenital sinus.
> Urinary bladder develops from the upper vesicourethral part of the urogenital sinus except the trigone.
> A cyst of the vagina, especially on the anterolateral vaginal wall, is usually Gartner's duct cyst (embryonic cyst).