1 GENITO-URINARY EMBRYOLOGY Genital and urological tracts are intimately associated developmentally and anatomically. All 3 layers contribute to development: 1. Intermediate Mesoderm nephric system male genital duct system wolffian (meso-nephric) ducts mullerian (para-meso-nephric) ducts portions of the gonads 2. Endoderm and Ectoderm cloaca and the cloacal membrane external genitalia Two stages of development: 1. Ambisexual/Indifference phase (week 1-6) initial stage of gender indifference - the primordia of both sex ducts appear and develop independently of genetic sex or hormonal influence 2. subsequent stage of male/female differentiation - the crucial stage of gonadal differentiation in which hormonal control of sex duct growth is paramount Although chromosomal sex is determined at the moment of fertilization, gonadal development will continue as female unless there is activation of the histocompatibility-Y (H-Y) antigen. Lateral mesoderm proliferates to form urethral and genital folds. A genital ridge forms on the ventromedial aspect of the genital fold and protrudes into the coelom. Primitive germ cells migrate into this region and evolve into the sexually bipotential gonads. The overlying epithelium projects into each gonad forming the primary sex cords. I. URETHRA Primitive Urogenital sinus develops week 4-6 from cloacal expansion of the hindgut Continuous superiorly with allantois forming the bladder The pelvic urethra forms o Membranous urethra in females o Membranous and prostatic urethra in males The definitive urogenital sinus forms 2 o Vagina vestibules in females o Penile urethra in males At the end of week 5, a wedge of mesenchyme - the urorectal septum - begins to descend separating the cloaca into a rectum dorsally and a urogenital sinus ventrally. The urorectal septum completes its descent fusing with the cloacal membrane to form the perineal body. II. DUCTS Initially 2 pairs of genital ducts: i. the mesonephric duct a. becomes the primary genital duct in the M ii. the para-mesonephric ducts a. main genital duct of the F Differentiation of the ducts is influenced by 2 testicular hormones: a) mullerian inhibiting substance polypeptide produced by the Sertoli cells. causes regression of the para-mesonephric duct (Mullerian). b) testosterone analogue produced by the interstitial cells of Leydig. Stimulates: masculine development of the Wolffian ducts, elongation of the genital tubercle to form a penis, formation of the penile urethra, fusion of the scrotal swellings, 3 development of the prostate and seminal vesicles. NB No gonadal hormones are required for the development of the female phenotype, thus if the testes do not function as male endocrine organs then the external genitalia will be female. The mesonephric duct (Wolffian) Elongates and becomes convoluted to form the epididymis. Caudally, it is encased in a thick muscular coat as the vas deferens. Distally forms an out-pouching that develops into the seminal vesicle. Beyond this it becomes the ejaculatory duct. In the male, the para-mesonephric duct degenerates except for a small cranial portion which becomes the appendix testis. The Para-mesonephric duct (Mullerian) 3 parts: a) cranial longitudinal portion - becomes the fallopian tube b) central transverse portion - becomes the uterine fundus and corpus c) caudal longitudinal portion - fuses with its counterpart on the opposite side to become the cervix of the uterus and the provisional vagina. A layer of mesenchyme around the para-mesonephric duct becomes the myometrium. The Mullerian tubercle forms where the fused lower portions of the Mullerian ducts push into the posterior wall of the urogenital sinus. The vaginal plate forms from “sinovaginal bulbs” present between the tubercle and the ducts themselves. The Mullerian tubercle is the site of the future hymen. 4 III. EXTERNAL GENITALIA By the end of the fifth week a pair of swellings called the cloacal folds develop on either side of the cloacal membrane These folds fuse just anterior to the cloacal membrane to form a midline swelling - genital tubercle o appears in the ventral midline between the cloacal membrane and the allantois Week 7 – fusion of the urorectal septum with cloacal membrane creates perineum Portion of the cloacal fold flanking the urogenital membrane is called the urethral fold A new pair of swellings, labioscrotal swellings appear on either side of the urethral folds Endodermal lined uretheral groove continuous with the definitive urogenital sinus extending onto the genital tubercle develops in the week 6 Urogenital membrane ruptures at the end of week 7 Male Undifferentiated external genitalia Female genital tubercle clitoris Urethral folds labia minora scrotum Labioscrotal fold labia majora Penile urethra Definitive uro-genital vestibule of Glans and shaft penis penile shaft / foreskin sinus vagina 5 In the Male Endodermal urethral groove becomes temporarily filled by endodermal urethral plate which then recanalises to 6 form an even deeper groove As the urethral plate disintegrates the urethral groove deepens and an anterior urethra is formed. The genital tubercle elongates forming the penis. The urethral groove lying ventrally does not reach the tip of the phallus. Initially blind ended Terminal portion of the urethra is formed by an ectodermal invagination from the tip of the glans The urethral folds fuse over the urethral groove to form the urethra and the midline raphe by week 14. The urethral folds also form the foreskin. The labioscrotal swellings fuse in the midline to form the scrotum and move posteriorly. One of the hallmarks of the masculinization process is the formation of the raphe scroti rather than the nonunited structures in the female. The corpora cavernosa differentiate at 13 weeks from consolidated mesenchyme in the dorsal portion of the phallus. The mesenchyme around the urethra becomes the corpus spongiosum. In the Female The genital tubercle bends caudally to form the clitoris. The urethral plate does not traverse this structure hence the urethra opens proximally. The labioscrotal fold and urethral folds do not fuse o The labioscrotal swellings elongate on each side to form the labia majora. o The urethral folds form the labia minora, The definitive uro-genital sinus forms the vestibule of the vagina. The prepucial folds and the corpus cavernosa of the clitoris form at 13 weeks. The prepucial folds form a hood, incomplete ventrally. The junction between ectoderm and endoderm is at the inner border of the labia minora. By the 3rd foetal month, the external genitalia are identifiable as female. 7 8