Developmental of female Developmental of female genital system genital system

By: E. SuryadiBy: E. Suryadi

Development of OvariesDevelopment of Ovaries In embryos lacking a Y chromosome, In embryos lacking a Y chromosome,

gonadal development occurs very slowlygonadal development occurs very slowlyAfter tenth week the characteristic cortex After tenth week the characteristic cortex

begins to develop.begins to develop.The primary sex cords do not became The primary sex cords do not became

prominent in the gonads of female prominent in the gonads of female embryos and then they degenerate.embryos and then they degenerate.

During the fetal period, secondary sex During the fetal period, secondary sex cords called cortical cords extend from the cords called cortical cords extend from the germinal epithelium into the underlying germinal epithelium into the underlying mesenchymemesenchyme

At about 16 weeks, the cortical cords At about 16 weeks, the cortical cords begin to break up into isolated cell cluster begin to break up into isolated cell cluster called primordial follicles. They consist called primordial follicles. They consist oogonium, surrounded by a single layer of oogonium, surrounded by a single layer of flattened follicular cells flattened follicular cells

During fetal the flattened follicular cells During fetal the flattened follicular cells change become cuboid , and the structure change become cuboid , and the structure is called a primary follicleis called a primary follicle

Development of GonadsDevelopment of Gonads

Molecular regulation...Molecular regulation... Spesific genes that induce ovarian development ---> Spesific genes that induce ovarian development --->

DAX1, located on the short arm of the X chromosome DAX1, located on the short arm of the X chromosome and acts by downregulating SF1 activity, thereby and acts by downregulating SF1 activity, thereby preventing differentiation of sertoli and leydig cells.preventing differentiation of sertoli and leydig cells.

The secreted growth factor WNT4 also contribute to The secreted growth factor WNT4 also contribute to ovarian differentiation, and its early expression in the ovarian differentiation, and its early expression in the gonadal ridge is maintained in female but gonadal ridge is maintained in female but downregulated in males.downregulated in males.

In the absence of MIS, the paramesonephric In the absence of MIS, the paramesonephric (m(mȕllerian) ducts are stimulated by estrogens to forms ȕllerian) ducts are stimulated by estrogens to forms the uterine tubes,uterus,cervix & upper vagina.the uterine tubes,uterus,cervix & upper vagina.

Estrogen also act on the ext.genitalia to form the labia Estrogen also act on the ext.genitalia to form the labia majora&minora,clitoris & lower vagina.majora&minora,clitoris & lower vagina.

Formation of Ovarian Primordial FolliclesFormation of Ovarian Primordial Follicles

Germs cells go on to differentiate into oogonia, proliferate, and Germs cells go on to differentiate into oogonia, proliferate, and enter the first meiotic division to form primary oocytesenter the first meiotic division to form primary oocytes

These meiotic oocytes stimulate adjacent somatic support cells These meiotic oocytes stimulate adjacent somatic support cells to differentiation into follicle cells (or granulosa cells) that then to differentiation into follicle cells (or granulosa cells) that then surround individual oocytes and form primordial follicles within surround individual oocytes and form primordial follicles within the ovarythe ovary

Follicle cells arrest further oocyte development until pubertyFollicle cells arrest further oocyte development until puberty

Formation of Ovarian Primordial FolliclesFormation of Ovarian Primordial Follicles

The absence of testosterone The absence of testosterone cause the disappearance of cause the disappearance of mesonephric ducts and mesonephric ducts and tubules, except a few vestigestubules, except a few vestiges

Two remnants, the epoophoron Two remnants, the epoophoron and paroophoron are found in and paroophoron are found in the mesentery of the ovary and the mesentery of the ovary and a scattering of tiny remnants a scattering of tiny remnants called Gartner’s cysts cluster called Gartner’s cysts cluster near the vaginanear the vagina

The mullerian ducts, in The mullerian ducts, in contrast, develop uninhibited, contrast, develop uninhibited, become fimbriae and oviductbecome fimbriae and oviduct

From 7th week to 5th month

Maturation and Maturation and DifferentiationDifferentiation

In FemaleIn Female- Oogonia/oocytes not enveloped by a - Oogonia/oocytes not enveloped by a granuloses cell layer become atreticgranuloses cell layer become atretic- begin at menarche (the first menstrual - begin at menarche (the first menstrual cycle)cycle)- Folliculogenesis/hormonogenesis/- Folliculogenesis/hormonogenesis/

steroidogenesis steroidogenesis

In maleIn male- Spermatogenesis- Spermatogenesis

three phases: metotic, meiotic, three phases: metotic, meiotic, spermiogenesisspermiogenesis

Changes during oogenesisChanges during oogenesis At birth the human ovaries contain about 1 At birth the human ovaries contain about 1

million oocytesmillion oocytes The complex of the ovum (oocyt) and its The complex of the ovum (oocyt) and its

surrounding cellular surrounding cellular as a follicle as a follicle During change from primordial follicle to During change from primordial follicle to

primary follicleprimary follicle- flattened granulosa cell become - flattened granulosa cell become cuboidal cuboidal granulosa cell.granulosa cell.- oocytes enlarge from - oocytes enlarge from ± 15± 15m to 100m to 100mm- oocytes begins to produce the zona - oocytes begins to produce the zona pelluzidapelluzida

Only about 400 oocytes will reach maturity Only about 400 oocytes will reach maturity and become ovulated and become ovulated

FOLLICULOGENESISFOLLICULOGENESIS

Under predominantly FSH stimulationUnder predominantly FSH stimulationFollicle will grow in size, from 150Follicle will grow in size, from 150m to m to

2-3 cm2-3 cmGranulosa and theca cell proliferate Granulosa and theca cell proliferate Increase oestrogen and progesteronIncrease oestrogen and progesteron

Three stage of Three stage of folliculogenesisfolliculogenesis

1.1. RecruitmentRecruitment

- the gonadotropin dependent- the gonadotropin dependent- some follicle leaves the restino - some follicle leaves the restino primordial poolprimordial pool- occurs during days 1-4, menstrual - occurs during days 1-4, menstrual cyclecycle

2. Selection2. Selection- to the species characteristic - to the species characteristic ovulatory ovulatory quotaquota

- mechanism unclear- mechanism unclear

- unknown criteria- unknown criteria

- days 5-7 of menstrual cycle- days 5-7 of menstrual cycle

3. Dominance3. Dominance- usually only one follicle- usually only one follicle- the dominant follicle secretes a - the dominant follicle secretes a substance, its called selectronsubstance, its called selectron- selectron to inhibit the - selectron to inhibit the development of development of potentially potentially competing folliclecompeting follicle- a week before ovulation- a week before ovulation

Development of The Genital Ducts Development of The Genital Ducts

The Indifferent Stage consist two pairs of The Indifferent Stage consist two pairs of genital ducts: genital ducts:

1.ductus mesonephridicus (Wolffian ducts) 1.ductus mesonephridicus (Wolffian ducts)

2.ductus paramesonephridicus (Mullerian 2.ductus paramesonephridicus (Mullerian

ducts) ducts)

Development of Genital DuctsDevelopment of Genital Ducts

Mesonephric duct Mesonephric duct epididymis , defferen epididymis , defferen duct & ejaculatory duct, seminal glandduct & ejaculatory duct, seminal gland

The Paramesonephric duct The Paramesonephric duct develop develop lateral to the gonads and mesonephric lateral to the gonads and mesonephric ducts, pass caudally, parallel to the ducts, pass caudally, parallel to the mesonephric ducts, until they reach the mesonephric ducts, until they reach the future pelvic region of the embryo, and to future pelvic region of the embryo, and to develop to the tuba uterina, and uterus.develop to the tuba uterina, and uterus.

Mullerian DuctsMullerian Ducts

Recall that the distal tips of the growing mullerian Recall that the distal tips of the growing mullerian ducts adhere to each other just before they contact ducts adhere to each other just before they contact the posterior wall of the pelvic urethra.the posterior wall of the pelvic urethra.

The wall of the pelvic urethra at this point form a The wall of the pelvic urethra at this point form a slight thickening called the sinusal tubercleslight thickening called the sinusal tubercle

Mullerian DuctsMullerian Ducts

The MD begin to fuse from their caudal tips cranially, forming a The MD begin to fuse from their caudal tips cranially, forming a short tube with a single lumen, called uterovaginal canal or short tube with a single lumen, called uterovaginal canal or genital canal, becomes the uterus and possibly contributes to genital canal, becomes the uterus and possibly contributes to the cranial portion of the vaginathe cranial portion of the vagina

The unfused cranial part of MD become the fallopian tubesThe unfused cranial part of MD become the fallopian tubes The tunnel shaped cranial opening become the infundibula of The tunnel shaped cranial opening become the infundibula of

the fallopian tubesthe fallopian tubes

Development of VaginaDevelopment of Vagina Vaginal epithel develop from endoderm of urogenital sinus and Vaginal epithel develop from endoderm of urogenital sinus and

fibromuscular wall tissues of vagina origin from mesenchym .fibromuscular wall tissues of vagina origin from mesenchym .

Female Genital Ducts and GlandsFemale Genital Ducts and Glands

Mullerian DuctsMullerian Ducts

The endodermal tissue of the sinusal tubercle in the posterior The endodermal tissue of the sinusal tubercle in the posterior urethra continues to thicken, forming a pair of evaginating urethra continues to thicken, forming a pair of evaginating swellings called the sinuvaginal bulbs that fuse to form the swellings called the sinuvaginal bulbs that fuse to form the vaginal plate which will become the inferior part of the vaginavaginal plate which will become the inferior part of the vagina

The endodermal membrane temporarily separates lumen of the The endodermal membrane temporarily separates lumen of the vagina from the base of the urogenital sinus (vaginal vestibule) vagina from the base of the urogenital sinus (vaginal vestibule) degenerates after the 5 degenerates after the 5thth month month the remnant persists as the remnant persists as the vaginal hymen the vaginal hymen

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EpoEpoööphoronphoronParoParoööphoronphoronOvarian ligament Ovarian ligament Atrophied mesonephric duct Atrophied mesonephric duct Cysts of GartnerCysts of GartnerHymenHymenSuspensory ligament of ovarySuspensory ligament of ovaryFallopian tube (ampulla)Fallopian tube (ampulla)Vesicular appendage (Morgani)Vesicular appendage (Morgani)UterusUterusRound ligament of uterusRound ligament of uterusVaginaVaginaInsertion of the round ligament Insertion of the round ligament of uterus at the genital swellingof uterus at the genital swelling

Development of Female External GenitaliaDevelopment of Female External Genitalia

Feminization of female external genital induced by Feminization of female external genital induced by estrogenestrogen, which produced by the placenta & fetal , which produced by the placenta & fetal ovaries.ovaries.

Growth of the phallus Growth of the phallus form the clitoris, at 18 weeks, form the clitoris, at 18 weeks, the urogenital folds join to form the urogenital folds join to form the frenulum ofthe frenulum of the the labia minora, labia minora,

The unfused parts of the urogenital folds form the The unfused parts of the urogenital folds form the labia labia minora.minora.

The labioscrotal folds fuse posteriorly to form the The labioscrotal folds fuse posteriorly to form the posterior labial comissureposterior labial comissure and anteriorly to form the and anteriorly to form the anterior labial comissureanterior labial comissure and and mons pubismons pubis

Female External GenitaliaFemale External Genitalia

Development of External GenitaliaDevelopment of External Genitalia

In the 5In the 5thth week, a pair of swelling called urogenital week, a pair of swelling called urogenital folds develop on either sidefolds develop on either side

There is an expansion of the underlying mesoderm There is an expansion of the underlying mesoderm flaking the anal membrane forming the anal foldsflaking the anal membrane forming the anal folds

A new pairs of swellings, the labioscrotal swellings A new pairs of swellings, the labioscrotal swellings then appears on either side of the urethral foldsthen appears on either side of the urethral folds

Development of External GenitaliaDevelopment of External Genitalia

Starting the 4Starting the 4thth month, the absence of month, the absence of testosterone in the female embryo, the testosterone in the female embryo, the primitive perineum doesn’t lengthen and the primitive perineum doesn’t lengthen and the labioscrotal and urethral folds don’t fuse labioscrotal and urethral folds don’t fuse across the midlineacross the midline

Male derivativeMale derivative Indifferent structureIndifferent structure Female derivativeFemale derivative

testistestis gonadgonad ovaryovary

SpermatozoaSpermatozoa Primordial germ cellsPrimordial germ cells OvaOva

Seminiferus tubulus Seminiferus tubulus (sertoli cells)(sertoli cells)

Sex cordsSex cords Follicular cellsFollicular cells

Efferent ductulesEfferent ductules Mesonephric tubulesMesonephric tubules EpoophoronEpoophoron

Epididymal duct, Epididymal duct, ductus defferensductus defferens

Mesonephric (Wolffian)Mesonephric (Wolffian)

ductduct

Degenerates (ovarian, Degenerates (ovarian, round ligament )round ligament )

Degenerates Degenerates Paramesonephric Paramesonephric (Mullerian) duct(Mullerian) duct

Uterine tubes, uterus, Uterine tubes, uterus, part of vaginapart of vagina

Bladder, protaste Bladder, protaste urethraurethra

Early urogenital sinusEarly urogenital sinus Bladder, urethra, Bladder, urethra, vaginavagina

Lower urethra, bulbo Lower urethra, bulbo urethral glandurethral gland

Definitive urogenital sinusDefinitive urogenital sinus Vestibule, Major Vestibule, Major vestibular glandvestibular gland

PenisPenis Genital tubercle = phallusGenital tubercle = phallus clitorisclitoris

Floor of penile urethraFloor of penile urethra Urogenital foldUrogenital fold Labia minoraLabia minora

ScrotumScrotum Genital swellingsGenital swellings Labia majoraLabia majora

Abnormal Development of Uterus Abnormal Development of Uterus