Development of external & internal genitalia by Dr.Preksha

development of external and internal genitalia ovaries embryology

1. DEVELOPMENT OF EXTERNAL & INTERNAL GENITALIA DR. PREKSHA JAIN DR. MEDHA NAGPURE

2. Embryonic structures involved are intermediate mesoderm & the cloaca INTERMEDIATE MESODERM : Part between paraxial & lateral plate mesoderm Forms bulging cranial to caudal = Nephrogenic cord 4 structures develop lateral to medial P aramesonephric duct Mesonephric duct Mesonephros Gonad DEVELOPMENT OF UROGENITAL SYSTEM

3. GONADS 4 th week Thickened mesothelium on medial side of mesonephros Gonadal ridges @ 7 th wk Divide into CORTEX & MEDULLA Migration of primordial germ cell along dorsal mesentery reach @ 6 th wk

4. 46XY 46XX INDIFFERENT GONAD TESTIS OVARY SRY GENE MIS PARAMESONEPHRIC DUCT TESTOSTERONE MESONEPHRIC DUCT DHT EXTERNAL GENITALIA ESTROGEN PARAMESONEPHRIC DUCT EXTERNAL GENITALIA

5. PARAMESONEPHRIC DUCT Mullerian ducts form 5-6 th week. Formed by invagination of coelomic epithelium. Wolffian ducts serve as migration template. If wolffian duct fails mullerian duct donot develop. Fuse with other side caudally in midline to form UTERO-VAGINAL CANAL & sheet of peritoneum which forms BROAD LIGAMENT Caudal end joins phallic part of UGS In females it forms tubes, uterus & upper 1/3rd of vagina In males remnants forms prostratic utricle (~uterus ) & appendix of testis

6. 3 phases of M ullerian duct development PHASES GENE Selection of cells in coelomic epithelium Lim 1 Epithelial invagination Wnt family Duct elongation Duct differentiation Pax2 Pax8

7. MALE EMBRYONIC STRUCTURE FEMALE Testis INDIFFERENT GONAD Ovary Seminiferous tubules CORTEX Follicles Rete testis MEDULLA Rete ovary Gubernaculum testis GUBERNACULUM Ovarian & Round lig Efferent ductules MESONEPHRIC TUBULES Epo & paraoophoron Duct & appendix of Epididymis Ductus deferens Ejaculatory duct & Seminal vesicle Ureter, renal pelvis, Collecting duct MESONEPHRIC DUCT Duct of epoophoron Duct of Gartner No homologous Same Appendix of testis PARAMESONEPHRIC DUCT Uterus, Tubes, upper 1/3 rd of vagina & Hydatid Bladder Urethra Prostate Prostatic utricle UROGENITAL SINUS Bladder Urethra Urethral & paraurethral glands Vagina

8. Penis Glans penis GENITAL TUBERCLE Clitoris Glans clitoris Ventral aspect of penis URETHRAL FOLDS Labia minora Scrotum GENITAL SWELLINGS Labia majora

9. UTERUS & TUBES Begins @ 7-8wk completes by 12 th wk EPITHELIUM: fused paramesonephric duct MYOMETRIUM: surrounding mesoderm increase in thickness & unfused parts embedded to form fundus TUBES: develop from unfused paramesonephric ducts FIMBRIAE: invagination of coelomic epithelium

10. CERVIX & VAGINA @ 20 th week condensation of stromal cells around fused mullerian duct forms cervix Part where Uterovaginal canal ( meso ) & Phallic part of UGS ( endo ) meet lead to formation of vaginal plate. Sinovaginal bulb form from endoderm Vaginal plate from mesoderm & endoderm Canalisation of vaginal plate Hymen( endo ) is junction of vagina plate & UGS

11. EXTERNAL GENITALIA Elongation of UG membrane occurs Mesoderm on both sides heap up to form primitive URETHRAL FOLDS later forms Labia Minora ( endo & ecto ) 3 elevations (9 weeks): GENITAL TUBERCLE forms clitoris GENITAL SWELLINGS forms Labia Majora UG membrane breaks leads to formation of VESTIBULE

12. 9 weeks 10 weeks 12-14 weeks

13. OVARY Genital ridges develop on medial side of mesonephros by thickening of coelomic epithelium Cords of cells(sex cords or medullary cords) grows into underlying mesoderm Primordial germ cells migrate to form oocytes Sex cord breaks forms masses that surround one oocyte to form PRIMORDIAL FOLLICLE INTERSTITIAL GLANDS differentiate from mesenchyme of gonad

14. DEVELOPMENT OF OVARY Stages: Indifferent gonad stage Differentiation Oogonal multiplication & oocyte formation Follicle formation

15. BIPOTENTIAL GONAD TESTIS OVARY TDF on SRY gene on Y AMH SOX9 FGF9 CORTICAL REGRESSION MEDULLARY PROLIFERATION Lack of SRY DAX1 WNT4 RSPO1 CORTICAL PROLIFERATION MEDULLARY REGRESSION LEYDIG CELLS SERTOLI CELL TESTOSTERONE WOLFFIAN DUCT DHT MALE EXTERNAL GENITALIA AMH MULLERIAN DUCT FEMAL EXTERNAL GENITALIA 2 wk later

16. 2.Differentiation Male phenotype depend on AMH & testosterone Female phenotype depend on absence of these products AMH Receptor gene mutation in 46XY – I nternal female genitalia External male genitalia Small amount of AMH in ovary help in oocyte maturation & follicular development Serum AMH levels correlate with follicles present & response to ovulation induction

17. LH HCG & ACTH 20 WEEKS STIMULATION OF LEYDIG CELLS TESTOSTERONE

18. 3.OOGONAL MULTIPLICATION & OOCYTE FORMATION 6-8wk 20 wk (7 million)

19. 4.Follicle formation

20. Ovary forms in lumbar region descends to true pelvis. Gubernaculum extend from ovary to labium majus . Attach at junction of tube & uterus. Persists as Round ligament DESCENT OF OVARY

21. Intermediate mesoderm: 3 rd week Pronephros : 4 th week & regress Mesonephros : 4 th week function @ 6-10 th week Metanephros : 4 th week function from 12 th week Mullerian ducts: 6 th week Primordial germ cells develop in yolk sac : 4 th Migrate : 6 th Gonads remain as indifferent : 6 th Interstitial cells produce testosterone : 8 th Sec sex cords: 10-12 th Primordial follicles: 16th Urethral folds: 3 rd mth External genitalia: 7 th and 9 th week Urorectal septum: 4 th and 7 th week Vagina: 20 th TIME TABLE OF EVENTS