emberiology

Embryology and anatomy of female genital tract

by Dr. Dalya M. Abdulrahman

Introduction:

An understanding of the development and anatomy of the female genital tract is important in the practice of gynecology. Both the urinary and genital systems develop from a common mesodermal ridge running along the posterior abdominal wall. It is important to remember that congenital anomalies of the genital tract may also be associated with congenital anomalies of the urinary tract.


Following fertilization the normal embryo contains 23 sets of chromosomes ,including 22 autosomes and one sex chromosomes from each parent. 46XY embryo will develop as a male 46XX embryo will develop as a female It’s the presence or the absence of the Y chromosome which determines whether the undifferentiated gonad becomes a testis or an ovary.

1. Genital ridge (proliferation of coelomic epithelium) 2. Mesonephric (Wolffian) duct (lateral to the genital ridge) 3. Paramesonephric (Mullerian) duct

Normal Sexual Determination And Differentiation

Genetic Sex
Gonadal Sex
Phenotypic sex
Undifferentiated Phase
Differentiation Phase

Gonads:The phase of indifferent gonads (Genital Ridge): 

The gonads do not acquire male or female morphological features until the 7th week of development. A pair of longitudinal ridges lie ventro-medial to the mesonephric kidney. These are epithelium covered condensations of mesenchyme & are called genital or gonadal ridges.

Neural tube Dorsal aorta Dorsal mesentery Mesonephros Gonadal ridges Gut

Gonadal Ridges


Germ cells start appearing in these ridges after 5th week. Primordial germ cells appear in the endoderm of the yolk sac. They migrate by ameboid movements, via dorsal mesentery, reach the genital ridges during 5th week & invading the genital ridges in the 6th week. If they fail to reach the ridges, the gonads do not develop.

Migratory Path Of Primordial Germ Cells From The Yolk Sac Along The Hindgut Mesentery, To The Urogenital Ridge At Approximately 5 Weeks

The covering epithelium proliferates and sends cluster of cells into the underlying mesoderm known as the cells of the sex cords. It is impossible to differentiate between the male and the female gonad. Hence the gonad is known as the indifferent gonad.
the germ cells
mesenchymal stroma (potential theca/Leydig cells).
sex cords (granulosa or Sertoli cells)

The phase of Gonadal Differentiation

The differentiation of the gonads into testis depends on the presence of sex determining region or gene (SRY) located on the short arm of the Y chromosome. Deletion of this SRY gene results in XY female.
Testis Differentiation sex determining region or gene (SRY)


Ovarian Differentiation Occur in the absence of Y chromosome and SRY protein it occurs two weeks later (about the 8th week).

Y chromosome contains the SRY (sex-determining region on Y) gene on its short arm. The protein product of this gene is a transcription factor that initiates a cascade of downstream genes that determine the fate of primordia of the sexual organs. The SRY protein is the testis-determining factor; its presence influences the male development, while its absence establishes the female development.

Ovary

If no Y chromosome is present, the gonad, by default, forms an ovary; the cortex develops, the medulla regresses, and oogonia begin to develop within follicles. The surface epithelium give rise to a second generation of cords, the cortical cords (secondary sex cords). These cords will split into cell clusters, each holding a primitive germ cell. Germ cell develop into oocyte and surrounding cord cells become a single layer of flat cells, the flolicular cells & whole structure as the primordial follicle.

44 + XY 44 + XX Y Influence Absence of Y

Indifferent Sex Testis Ovary Medullary cords develop Medullary cords degenerate No cortical cords Cortical cords develop Thick tunica albuginea No tunica albuginea
Y Chromosome Influence


The oogonia are derived from the primitive germ cells by a series of about 30 mitoses, for fewer than the number required for spermatogenesis. Beginning at about the end of the third month, the oogonia enter meiosis I, but this this process is arrested at a stage called dictyotene, in which the cell remains until ovulation occurs many years later. Many of the oogonia degenerate before birth, and only about 400 mature into ova during the 30 years or so of sexual maturity of the female.

(4th month) (Oogonia) Germ cell surrounded by a single layer of epithelial cells

Oogonia
Primary Oocytes 1st meiotic division and arrest in prophase
(20th week) The ovary contains about 7 million germ cells Degeneration and atresia begins
At birth approximately 2 Million germ cells remain.


Descent of the Ovaries
Descent of the gonads in female is much less. Ovaries move and settle just below the rim of the true pelvis. At the same time as the ovary descends extraperitoneally into the abdominal cavity, two ligaments develop and these appear to help control its descent: Cranial genital ligament forms the suspensory ligament of the ovary, where as the caudal genital ligament forms the ligament of the ovary proper and the round ligament of the uterus. The later extends into the labia majora.

Genital Ducts: Indifferent Stage

Both male and female embryos start with two pairs of genital ducts: the mesonephric ducts and paramesonephric ducts. The Mesonephric (Wolffian) duct: run on either side of the primitive gut as a longitudinal ridge, covered by the coelomic epithelium. The Mullerian duct (Paramesonephric ducts): Runs lateral to the Mesonephric duct. At its caudal part the Mullerian ducts pass medially across the front of the Wolffian ducts. The Mullerian ducts, from each side, meet and fuse as a single solid rod of cells. They further extend caudally until they make contact with the urogenital sinus; produce a prominent elevation in its posterior wall, known as the Mullerian tubercle.

Indifferent Stage

Genital Ducts (6th Week)
Male
Female

Molecular Regulation of Genital Duct Development

Male sex determination is controlled by the SRY gene, the testis determining factor on the Y chromosome. SRY gene product act as a transcription factor that induces expression of downstream genes leading to production of Mullerian inhibiting substance (MIS), and testosterone .

Stage of Ductal differentiation (8 weeks):

Differentiation of male internal organs - The Mullerian Inhibiting Hormone (MIH) (Sertoli cells ): responsible for regression of the ipsilateral paramesonephric ducts - Testosterone (Leydig cells): responsible for development of the mesonephric duct into the male internal genitalia

Differentiation of Female Internal Organs In the absence of testes (MIF and testosterone) the mesonephric system regress and the Mullerian duct develop to give the fallopian tube, uterus, and upper vagina.


The paramesonephric (mullerian) duct:
The coelomic epithelium lateral to the Wolffian duct is invaginated to form the Mullerian duct which grows caudally, at first it is solid, but later it becomes canalized It deviates more and more medially till it meets its fellow of the opposite side . The septum between the 2 Mullerian ducts disappear . The proximal parts of the Mullerian ducts form the fallopian tubes , while the distal parts meet together to form the body and cervix of the uterus and the upper 4/5 th of the vagina . The stroma and muscles develop from the surrounding mesoderm .

Uterus

Genital Ducts in FemaleA(After 8th week), B(After descent of Ovary)


Remnants of the mesonephric (wolffian) ducts that may persist in the anterolateral vagina or adjacent to the uterus within the broad ligament or mesosalpinx.

Vagina

The Mullerian ducts reach down to the urogenital sinus and at the meeting point , form the Mullerian tubercle which meet a pair of endodermal sinovaginal bulbs which arise from the urogenital sinus . These evaginations, the sinovaginal bulbs, proliferate and form a solid vaginal plate. By the 5th month, the vaginal plate is entirely canalized to form vagina. The lumen of the vagina remains seperated from the urogenital sinus by a thin tissue plate, the hymen, which consists of the epithelial lining of the sinus and a thin layer of the vaginal cells. It usually develops a small opening during perinatal life.

9 Weeks 12 Weeks Newborn

Vagina

Development of the External Genitalia:

There is a common indifferent stage consisting of two genital folds, two genital swellings and a midline anterior genital tubercle.
The Phase of undifferentiated external genitalia


Differentiation to male phenotype:
The testis begins secretion of testosterone by the 8-9th week. masculinization of the genitalia is observed about a week later (the 10th week) and is completed by the 14th week. However the target cells of the external genitalia must be able to convert testosterone to its active product Dihydrotestosterone (DHT) under the influence of the intracellular enzyme 5 alpha reductase

Differentiation to female phenotype:

In the absence of DHT the bipotential external genitalia differentiate into female

Clitoris develops from the genital tubercle (by slight elongation) Labia minora develop from the genital folds (by remaining separate) Labia majora develop from the genital swellings (by enlarging greatly) Vestibule develops from the lower most part of the urogenital sinus.

External Genitalia In Female

5 Week Embryo Newborn

Glans penis Glans clitoris Urethral groove Urethral orifice Vestibule of vagina Labia minora Labia majora Scrotal raphe Scrotum Anus
External Genitalia of 12 Week Old Fetus
Female
Male

Summary of Normal Sex Differentiation

genetic sex is determined at fertilization. testes develop in XY fetus, ovaries develop in XX fetus. XY fetus produces MIS and androgens and XX fetus does not. XY fetus develops Wolffian ducts and XX fetus develops Mullerian ducts. XY fetus masculinizes the female genitalia to make it male and the XX fetus retains female genitalia.

Gonadal development

SRY-gene (TDF) Short arm of Y chromosome
Bipotential Gonad
2 X chromosomes
Receptors For H -Y antigen
OVARY
TESTES
Present
Absent


Leydig cells
Sertoli cells
Testosterone
Mullerian inhibiting factor
Wollfian duct
5a-reductase
Urogenital sinus
Regression of Mullerian ducts
Male external genitalia
Male internal Genital organs
DHT
TESTIS
Male development

Urogenital sinus

Female external genitalia . Lower part of vagina
OVARY
Mullerian ducts
Female internal genital Organs . Most of upper vagina . Cervix and uterus . Fallopian tubes
Neutral Development
Absence of androgen exposure
Female development


Anatomy
EXTERNAL GENITALIA (the vulva) include ; 1-The mons pubis 2- The labia majora 3- The labia minora 4- The clitoris 5- The vestibule and the vestibular orifice 6- The greater vestibular glands

Bartholin’ glands Bartholin's glands, each about the size of a small pea, lie at the base of each bulb and open via a 2 cm duct into the vestibule between the hymen and the labia minora. Some times the ducts of this gland obstruct leading to Bartholin cyst and if infection develop it may lead to Bartholin abscess.

Internal reproductive organs

1-The vagina 2-The uterus 3-The fallopian tubes 4-The ovaries

The vagina

* It is a fibromuscular canal lined with stratified squamous epithelium . It is longer in the posterior wall (9 cm) than anteriorly (7 cm). The vault of the vagina is divided into 4 fornices ; posterior, anterior and two lateral. *The vaginal walls are rugose with transverse folds *It has no glands. *The epithelium is thick and rich in glycogen, the growth of Doderlein's bacillus a normal commensal of the vagina that breaks down the glycogen to form lactic acid, producing a PH of around 4.5

The vagina

Age changes #At birth, the vagina is under the influence of maternal oestrogens, so the epithelium is well developed. After a couple of weeks, the effects of oestrogen disappear and the PH rises to 7 and the epithelium atrophies. # At puberty, the reverse occurs. # At the menopause, the vagina tends to shrink and the epithelium atrophies

The uterus

It is a fibromuscular organ & in non-pregnant state is situated entierly within the pelvis. Pre-pregnancy; 7*5*3 cm, weight 70 g. Full term; 30*25*20 cm, weight 1000 g. It consist of The corpus (body) The cervix

The corpus of uterus

It is the upper part of the uterus consist of : 1-the fundus, the uppermost part. 2-cornu, which is the site of insertion of the Fallopian tube. 3-the isthmus, when uterus tapers to a small central constricted area, ends by attaching to the cervix. The constriction at the isthmus where the corpus joins the cervix is the anatomical internal os. Uterus is in anteflexion and anteversion position. In around 20% of women, this tilt is not forwards but backwards-retroversion and retroflexion. The uterus consists of 3 layers *peritoneum; the outer serosol layer; laterally it spreads out to form the leaves of the broad ligament. *myometrium; the middle muscular layer; *endometrium; the inner mucous layer; covered by a single layer of columnar epithelium . This epithelium is under go cyclical changes and lost due to effects of pregnancy & menstruation.


The uterine support
Uterus is supported by ligaments: 1-transverse cervical( cardinal ligaments) 2-round ligament 3-uterosacral ligaments.

The cervix

Is a narrower than the body of the uterus approximately 2.5-3 cm in length It consist of two parts : * supra vaginal part: lined with columnar ep. *vaginal part :protruding into the vagina, lined with stratified squamous ep. The squamocolumnar junction is also known as the transformation zone.

The cervix

Age changes * After birth, the disappearance of maternal oestrogens causes the uterus to decrease in length by around one third and cervix is then twice the length of the uterus. *At puberty, the corpus grows much faster and the size ratio reverses. *After menopause, the uterus atrophied, the mucosa becomes very thin, the glands almost disappear & the wall becomes less muscular.

The fallopian tube (oviduct)

Each tubes about 10 cm long The tubes convey the ovum from the ovary towards the uterus & its the site of fertilization which provides oxygenation & nutrition for sperm, ovum & zygote. It is distinguished in to 4 parts: 1-interstitial part 2-the isthmus 3-ampulla 4-infundibulum

The ovaries

The blood supply
1-Ovarian A. 2-Uterine A. 3-Vaginal A. 4-Internal pudendal A

The lymphatic drainage

***Ovaries and tubes_____para aortic LN. ***Uterus, cervix and upper⅔ of vagina____internal iliac, obturator and external iliac LN, common iliac and para aortic LN. ***Vulva, lower⅓ of vagina.___superficial inguinal and femoral LN


The nerve supply
*Pudendal nerve (S2,3,4) Sensory fibers from the mons and labia also pass in the ilioinguinal and genitofemoral n. to the 1st lumber root. *Posteriofemoral cutaneous n. *Sympathetic n. fibers of the pre aortic plexus *Para sympathetic fibers from S2, S3, S4.