1 Development of the female Reproductive System Dr. Susheela Rani
2 Genital System Gonads Internal genitals External genitals
3 Determining sex chronology of events Genetic sex Determined at fertilization Gonadal sex 6 th week Phenotypic sex Behavioural Sex Differentiation of Psyche - Preoptic and Median region of Hypothalamus
4 Genetic Sex Genetic sex of an embryo is determined at the time of fertilization, depending on whether the spermatocyte carries an X or a Y chromosome.
5 The Master Gene that determines Gender SRY (Sex determining Region Y gene) Has a testis-determining effect on the indifferent gonads. Small gene (a single exon) Localized on the shorter arm of the Y chromosome (Yp) Gets expressed in the gonadal cells Controls a whole number of further genes on the autosomes as well as on the X chromosome. Causes development of Testes
6 Pseudo autosomal regions PAR1 and PAR 2 Yellow Heterochromatin redundant DNA sequences Pink SRY Region for Sex Determining Gene- Dark red ZFY, Y linked Zinc Finger Protein Orange Spermatogenesis Genes in long arm Azoospermia factor AZF Telomeres green Centromeres - Blue
9 It is not the number of gonosomes that is decisive for the gender, but rather the presence or absence of the Y-chromosome
10 Aneuploidy and Euploidy of Gonosomes Karyotype Phenotypic Gender Gonad Syndrome Fate 45, XO Female Ovaries Turner s Atrophy of Ovaries in the fetus 45, YO Absence of X chromosome is lethal 46, XX Female Ovaries Normal Woman 47, XXX Female Ovaries Normal fertility Normal Development Normal Development 46, XY Male Testes Normal Man Normal Development 47, XXY Male Testes Klinefelter s Small Testis Aspermatogenesis 47, XYY Male Testes Normal fertility Normal Development
11 Gender by Ultrasound Earliest gestational age that fetal gender may reliably be determined CRL 60 mm (gestational age 12+2)
12 Development of the Gonads
13 Primordial Germ Cells Primordial germ cells originate in the epiblast 3 rd week PGC migrate and reside among the endodermal cells in the wall of the yolk sac close to allantois. 4 th week, - Migrate by amoeboid movements along the dorsal mesentery of the hind gut 5 th week Reach the genital ridge 6 th week Reach the primitive gonads
15 Development of the Gonads The Urogenital ridge arises from the Intermediate mesoderm It consists of: Nephrogenic cord - Urinary apparatus Genital ridge Gonads The genital ridge extends from the upper thorax to claoca. Middle part develops into gonads Cranial and caudal parts form the Gubernaculum
16 In the female, the upper gubernaculum forms the suspensory ligament of ovary. The lower gubernaculum extends from the lower pole of the ovary as the ovarian ligament and then to the uterine tube angle, where it continues as the round ligament of uterus
17 Indifferent Gonad Shortly before and during arrival of PGC, the epithelium of the genital ridge proliferate, penetrate the underlying mesenchyme. They form the primitive sex cords In both male and female embryos, these cords are connected to surface epithelium and it is impossible to differentiate between the male and female gonad. This Gonad has a Cortex and Medulla
18 Differentiation of Ovaries The differentiation of the ovaries happens at 8weeks (later than that of the testes. Primitive Ovary has 2 regions Cortex, containing all the elements of the parenchyma Medulla, which shares the elements of the stroma with the cortex.
19 Development of Stroma In female embryos with an XX sex chromosome complement and no Y chromosome, primitive sex cords dissociate into irregular cell clusters These clusters, containing groups of primitive germ cells, occupy the medullary part of the ovary. Later, they disappear and are replaced by a vascular stroma that forms the ovarian medulla
20 Development of Cortex 4 th month Surface epithelium proliferates and penetrates the underlying mesenchyme - forms a second generation of cords, cortical cords These cords split into isolated cell clusters. 5 th month - Each cluster has oogonium with a layer of epithelial cells called follicular cells. This constitutes the Primordial follicle which contains oocytes that have entered into the prophase of the first meiosis
21 Germ cells in Ovary 70 L at 20 weeks 3 L at birth 30,000 at Puberty 300 are used from Puberty to Menopause
22 Internal genital Organs
23 Formation of uterus 7 th to 8 th week Up to the 7th week two canal systems on each side exist in both sexes. In the 8th week the paramesonephric ducts (Müller) fuse in the lower portion after they have crossed medially on both sides of the mesonephric duct (Wolff).
24 Formation of Uterus after 8 weeks Formation of the utero-vaginal canal through fusion of the lower section of the two paramesonephric ducts From the upper section - on both sides - arise the fallopian tubes with their ampullae.
25 End of 3 rd month The separating wall dissolves in the uterus and the vagina. The uterus lengthens and is subsequently canalized. Out of the lower section arises the upper part of the vagina. It joins with the vaginal lamina, which arises from the urogenital sinus and forms the lower portion of the vagina.
26 Female sex organs 7 th week The utero-vaginal canal comes up against the urogenital sinus and forms the sinu-vaginal eminence.
27 Female sex organs 12 th week This sinu-vaginal eminence becomes thicker due to epithelial proliferation. This also leads to a epithelial proliferation in the SUG epithelium. Together they form the vaginal plate.
28 Female sex organs 3 rd month Canalization of the vaginal plate
29 Female sex organs- 5 th month Vaginal canal is completely canalized, but the lumen is separated from the SUG by the hymen.
30 Female sex organs 9 th month Normally, the hymen tears open at the time of birth. The uterus and the vagina then have a connection to the vaginal vestibule.
31 The Exgternal Genitalia
32 Indifferent Ext Genitalia 6 th week In front, the cloacal membrane is delimited by a swelling, the future genital tubercle, that at the rear continues in the two cloacal folds.
33 Indifferent Ext Genitalia 7 th week Urorectal septum subdivides the cloacal membrane into urogenital and anal membranes.
34 Indifferent Ext Genitalia 9 th week From the cloacal folds around the urogenital orifice arise the urethral folds and, from the one around the anal orifice, the anal folds. Outside the urethral folds a further prominence arises on both sides, the genital swelling. It is important to remember that the morphology of the external genitalia in both sexes is very similar up to the 9th week.
35 Differentiated female genitalia 10 th week In the female, the genital tubercle lengthens only a little and shrinks again while forming the clitoris. The urethral folds do not fuse and the urogenital sinus remains wide open.
36 Differentiated female genitalia 12 th -14 th wk The urethral folds do not fuse the labia minora arise from them. From the genital swellings arise the labia majora. They fuse only in the rear part and form the posterior labial commissure that is continued towards the rear by the perineum.
37 ESHRE Classification of Uterine anomalies
40 Disorders of Sexual Development 46XX DSD 46XY DSD Sex Chromosome DSD
41 Disorders of sexual development classification
42 Disorders of Sexual Development 46XX DSD 46XY DSD Sex Chromosome DSD
43 46XX DSD Disorders of Gonadal Devpt. Androgen Excess Other disorders
44 Disorders of Gonadal Devept Ovotesticular DSD - True Hermophroditism, both testis and Ovary, Ext Genital devept depending on level of androgens Testicular DSD Sex Reversal, Abnormal Inactivating mutation of genes coding for Testes, SRY + SRY -, Infertile males or Ambiguous genitalia Gonadal Dysgenesis Primary amen, Hypogonadotropic, hypogonadism, streak gonads, problem with autosomes involved in gonadal devpt.
45 46XX DSD Disorders of Gonadal Devpt. Androgen Excess Other disorders
47 Virilization of Ext. Genitalia Partial Complete
48 Disorders of Sexual Development 46XX DSD 46XY DSD Sex Chromosome DSD
49 46XY DSD Disordes of Testicular devpt Disorders of Androgen synthesis / Action
50 Disorders of Testicular Devpt Complete Gonadal Dysgenesis Swyer syndrome, female despite Y, Streak gonads, No AMH, No Androgens, Primary Amen at Pubery Partial Gonadal dysgenesis Testicular regression Normal devpt, torsion of testis in IU life, regression, absent testes at birth
51 Disorders of Androgen synthesis/ action Androgen synthesis defect LH Receptor defect AIS 5a reductase deficiency Disorders of AMH Male with Hernia uterine Inguinale
52 Androgen Insensitivity Syndromes Partial androgen insensitivity with descended testes in bifid labioscrotal folds Less severe partial androgen insensitivity with severe hypospadias and maldescent of testes
53 Hernia Uterine Inguinale
54 Disorders of Sexual Development 46XX DSD 46XY DSD Sex Chromosome DSD
55 Others - Disorders of Sex Chromosome 45,X0 Turner s and variants 47,XXY Kilnefelters and variants 45,X, 46,XXy MGD 46,XX/46, XY Chromosomal Ovotesticular DSD
59 Differentiation of female sex organs 7th week differentiation begins Mesonephric duct and its tubules atrophy Embryonic remnants of the mesonephric duct remain in the form of the epoöphoron, the paroöphoron at the level of the mesovarium, and a row of small cysts of Gartner. Paramesonephric duct develops further Upper nonfused portions Fallopian tubes Lower fused portion Uterovaginal Canal The septum in between disappears at the end of the 3rd month.
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