male genital tract Normal sexual development of males and females Abnormalities of sexual development Objectives: to describe the normal embryology of male and female sexual differentiation to explain the major characteristics of those with intersex problems to explain the major characteristics of the common developmental abnormalities of both female and male genital tracts Sexual Differentiation Normal sexual development Requires coordinate interplay Correct chromosome complement and composition Proper migration of germ cells from yolk sac to urogenital ridge for initial induction Normal sexual development Requires coordinate interplay Appropriate hormone production by gonad Proper response by target organs to secreted hormones Normal sexual development Y chromosome of males leads to formation of testis SRY antigens of primitive gonad initiates determination into testis Only Genital ridge contains receptors for SRY antigens SRY antigen binding with genital ridge receptors: responsible for differentiation into testis Normal sexual development Medullary cords of primitive gonad differentiation into seminiferous tubules Sertoli cells of seminiferous tubules develop and begin producing MIS causing regression of mullerian ducts Differentiation of interstitial cells into Leydig cells which produce testosterone Normal sexual development Testosterone stimulates development of wolffian duct system to form vas deferens, seminal vesicles and epididymis Testosterone reduced to dihydrotestosterone which regulates development of external genitalia in males Normal sexual development Absence of Y chromosome and SRY antigens Primitive gonad differentiates into ovary Female development of mullerian duct system and external genitalia: an autonomous process Normal female not exposed to MIS Mullerian ducts form fallopian tubes, uterus, cervix and upper portion of vagina Absence of testosterone causes regression of wolffian ducts Normal sexual development Absence of Y chromosome and SRY antigens Absence of dihydrotestosterone Genital tubercle forms clitoris In males: glans penis Genital folds form labia minora In males: penile urethra Genital swellings form labia majora In males: scrotal sacs Urogenital sinus forms lower vagina Clinical findings in a newborn infant that raise the possibility of intersexuality Apparent Male Bilateral nonpalpable testes in a full- term infant Hypospadias associated with separation of the scrotal sacs Undescended testis with hypospadias Intermediate Ambiguous genitalia Clinical findings in a newborn infant that raise the possibility of intersexuality Apparent female Clitoral hypertrophy of any degree Foreshortened vulva with single opening Inguinal hernia containing a gonad ambiguous genitalia according to gonadal histology 1. Ovary
CAH
Placental aromatase deficiency
Maternal source of virilization
ambiguous genitalia according to gonadal histology 2. Testis Leydig cell hypoplasia Testosterone biosynthesis defect 5-Α -reductase deficiency Androgen insensitivity ambiguous genitalia according to gonadal histology Ovary and testis True hermaphroditism 4. Dysgenetic gonads Gonadal dysgenesis Denys-Drash and Frasier syndromes Smith-Lemli-Opitz syndrome Camptomelic dwarfism Initial evaluation of ambiguous genitalia Inter-sex problems Male pseudohermaphrodite Female pseudohermaphrodite Dysgenetic gonads True hermaphrodite Male pseudohermaphrodite Androgen insensitivity syndrome Abnormal Prenatal Abnormal Prenatal Differentiation Differentiation Sex Chromosome and Sex Chromosome and Hormonal Disorders Hormonal Disorders Androgen Insensitivity Androgen Insensitivity Syndrome Syndrome 46, XY At puberty, breast Undescended testes development and other Lacks a normal set of either signs of normal female male or female internal sexual maturation appear, structures but menstruation does not Normal female genitals and a occur. shallow vagina Female Sterile DHT-deficient males Abnormal Prenatal Differentiation Sex Chromosome and Hormonal Disorders DHT-deficient males 46, XY Undescended testes at birth; testes descend at puberty Vas Deferens, seminal vesicles, and ejaculatory ducts, but no prostate; partially formed vagina. Ambiguous at birth (more female than male); at puberty, genitals are masculinized. Female pseudohermaphrodite fetally androgenized females Abnormal Prenatal Abnormal Prenatal Differentiation Differentiation Sex Chromosome and Sex Chromosome and Hormonal Disorders Hormonal Disorders Fetally Androgenized Females Fetally Androgenized 46, XX Females Ovaries Normal female (individuals Normal female with adrenal malfunction Ambiguous (typically more must be treated with male than female) cortisone to avoid Fertile masculinization. Female, but significant level of dissatisfaction with female gender identity; very oriented toward traditional male activities. Dysgenetic gonads True hermaphrodite Abnormal Prenatal Differentiation Hermaphrodites True hermaphrodites. Exceedingly rare individuals who have both ovarian and testicular tissue in their bodies; their external genitals are often a mixture of male and female structures. Developmental anomalies of female genital tract Cloaca Urogenital sinus Vaginal anomalies Cervical anomalies Uterine anomalies Vaginal anomalies Cloacal malformation Urogenital sinus Vaginal atresia Vaginal anomalies Embryology Tissue origins for internal genital and urinary structures Mullerian ducts Fallopian tubes Uterus Upper third vagina Urogenital sinus Lower third vagina Metanephric ducts ureters Final anatomy of the female genital tract results from pairing, fusion and recanalization of the mullerian ducts, which grow caudally to join cloaca Vaginal anomalies Cloacal malformation Single opening on perineum with no separate opening for vagina or anus Flat labia Phallus small Sex rearing depends on size of phallus Vaginal anomalies Vaginal anomalies Urogenital sinus defects occur in normal females because of failure of urethra and vagina to separate Normal rectum Uterus bicornuate Results from failure of fusion of mullerian ducts to form mullerian tubercle and vaginal plate Takes place after urorectal septum separates rectum from urogenital sinus Vaginal anomalies Embryology Congenital androgen insensitivity syndrome Bilateral cryptorchid testes Elaborates normal mullerian inhibitory substance Only distal third vagina forms Vaginal anomalies Embryology Urogenital sinus and cloacal malformation Caudal regression syndromes Can present with variety of vaginal, bladder, renal and rectal anomalies Urogenital sinus Mullerian ducts do not fuse to form mullerian tubercle Vaginal plate not formed Vaginal anomalies Vaginal atresia Complete Proximal Distal Vaginal anomalies Vaginal atresia Complete Failure of mullerian ducts to reach urogenital sinus Fallopian tubes normal Uterus bicornuate and rudimentary Ovaries always normal Vaginal anomalies Vaginal atresia Proximal Result of failure of mullerian ducts to fuse to form mullerian tubercle Fallopian tubes, uterus and cervix hypoplastic or absent Vaginal anomalies Vaginal atresia Distal Sinovaginal bulbs originate from urogenital sinus forming vaginal plate Failure of proliferation of sinovaginal bulbs Distal vaginal atresia Cervix, uterus and fallopian tubes normal Vaginal anomalies Vaginal atresia Manifestations In infancy Hydrocolpos Hydrometrocolpos At menarche, Hematocolpos Hematometrocolpos Large midline mass Sharp, intermitent abdominal abdominal pain Present among patients with distal vaginal atresia Absent among patients with proximal vaginal
atresia, vaginal or uterine hypoplasia or
agenesis Vaginal anomalies Vaginal atresia Meyers-Rokitansky syndrome Congenital absence of vagina combined with abnormal or absent uterus Features Primary amenorrhea with congenital absence of vagina 46, XX karyotype Uterus varies from complete to rudimentary bicornuate cords to complete absence Normal ovarian function and ovulation Normal breast development and body configuration Frequent association of renal, skeletal and other congenital malformations Uterine anomalies Not symptomatic during childhood Problems related to infertility or complications of pregnancy Uterine anomalies Cervical atresia Hypoplasia of uterus Uterine aplasia Uterine duplication Uterine tube duplication Uterine anomalies Cervical atresia Rare Failure of development and canalization of cervical portion of fused paramesonephric ducts Uterine anomalies Hypoplasia of uterus Uterine aplasia Normal ovaries Well-developed female characteristics and cyclical breast changes Amenorrhea rare Uterine anomalies Unicornuate uterus Aplasia of one paramesonephric duct Accompanying fallopian tube usually absent or rudimentary Uterine anomalies Uterine duplication Caused by abnormal fusion of paramesonephric ducts Genital folds fail to unite normally Result: Complete bicornuate uterus with two cervices Duplication of uterine horns Uterine anomalies Uterine tube malformations Cause sterility or abnormal pregnancy Small supernumerary or accessory tubes attached to fimbriated ends Developmental anomalies of male genital tract Testicular anomalies Disorders of penis Disorders of scrotum Disorders of the inguinal canal Disorders of penis Disorders of penis Disorders of scrotum Empty scrotum Retractile testis Ectopic testes(3%) Dysgenetic or atrophic testes(5%) Absent testes(3%) True undescended testes(89%) Disorders of the inguinal canal inguinal anatomy Thank you. Table 1. Simplified classification of testicular germ cell tumors Infantile tumors Teratoma (mature) Yolk sac tumor Gonadoblastoma Tumors of young adult age Preinvasive lesion: Carcinoma in situ (CIS, gonocytoma) Seminoma (classic) Nonseminoma Embryonal carcinoma Teratoma Mature Immature With malignant transformation Extra-embryonic elements Choriocarcinoma Yolk sac tumor (endodermal sinus tumour) Combined tumor (elements of both seminoma and nonseminoma) Spermatocytic seminoma (spermatocytoma