Talk:2009 BGD-B Lecture Sexual Differentiation: Difference between revisions
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Revision as of 16:45, 27 May 2009
Development of the Genital System Dr Mark Hill Cell Biology Lab, SOMS Room G20 Wallace Wurth Bldg m.hill@unsw.edu.au UNSW Copyright Notice
Background
Notes
Fertilization
Week 1
Gastrointestinal Tract
Kidney
Endocrine
Urinary Bladder - early
Endoderm Yolk sac, yolk stalk, gastrointestinal tract Hindgut Allantois extending into connecting stalk
Movie: Hindgut - Urogenital Sinus Urinary Bladder - Septation Cloaca divided (week 6) Urorectal septum Posterior- rectum Anterior- urogenital sinus Continuous with allantois Apex of developing bladder Urachus Median umbilical ligament
Sex Chromosomes
X Chromosome
1400+ genes
150 million base pairs
95% determined
Chromosome Y
200+ genes
50 million base pairs
50% determined
Sex Determination
Humans (week 5-6)
Germ cells migrate into gonadal ridge
Gonads (male/female) identical at this stage
Indifferent
Gonad development dependent on sex chromosome
Y testes
No Y ovary
DNA with SRY Protein
SRY protein binds DNA
Testes determining factor (TDF)
Transcription factor
Bends DNA 70–80 degrees
Black
SRY protein HMG box
Red coil
DNA double helix
After Haqq et al. 1994 and Werner et al. 1995
SRY on Gonad Development
Gonad
gastrulating mammalian embryo
cells signaled by neighbours
form primordial germ cells (pgc)
migrate into genital ridges which develop into gonads
Primordial germ cells develop into
eggs, if gonad is becoming an ovary
sperm, if gonad is becoming a testis
Gonad will develop into an ovary unless its somatic cells contain a Y chromosome
Carnegie stage 13/14
Kidney 3 Stage Development
Pronephros, Mesonephros, Metanephros
Nephrons Movie: Germ Cell Migration Internal Genital Organs All embryos form paired Nephric duct Mesonephric duct (Wolffian) See kidney development Paramesonephric duct (Mullerian) Humans 7th week Invagination of coelomic epithelium Cord grows and terminates on urogenital sinus Male Gonad (testes) secretes Mullerian duct inhibitory factor (MDIF) Causes regression of paramesonephric duct Testosterone Retains mesonephric duct Female - opposite Movie: Germ Cell Migration Movie: Germ Cell Migration Movie: Germ Cell Migration SRY on Gonad Development Differentiation of Human Gonads Movie: Gonad Development Gonad Differentiation Overview Male Mesonephric Duct (st22) Movie: Bladder Fetal Testis Infant Ovary Infant Ovary Ovary - Germ Cell Numbers External Genitalia Internal Genital Tract Female - paramesonephric - uterus Male - mesonephric - ductus deferens External Genital Organs All embryos initially same (indifferent) Testosterone Differentiates male External Genital Organs External Genitalia Hormone Dependent Genitalia Male Hormone dependent anatomy Genital Ligaments Movie: Gonad Descent Both male and female gonads descend See also Abnormalities - Cryptorchidism
Puberty - Hormone Axis LH & FSH Difference in timing increased gonadotrophin secretion and stimulate gonadal maturation rise in testosterone and estradiol secretions in males and females respectively positive feedback of estradiol in females also occurs during puberty Tanner Stages - External Genitalia Tanner Stages - Mammary Tanner Stages Genital Abnormalities Chromosomal Hermaphroditism Gonadal Dysfunction Tract Abnormalities External Genitalia Gonadal Descent Chromosomal Turner’s Syndrome Monosomy XO 99% non-viable embryos Fail to sexually mature at puberty Klinefelter’s Syndrome 47, XXY Begin normal male, become infertile Tall, mental dullness, behaviour problems Males 46, XX Develop as male, infertile adults Part of SRY gene located on one X Sex Reversal in Humans Hermaphroditism True 46,XX Gonads both ovary and teste tissues Ovotestes or ovary and testes Male Pseudohermaphrodites 46,XY Gonads of one sex, external genitalia of opposite Various causes Female Pseudohermaphrodites 46,XX Gonads are ovaries, external genitalia ambiguous Hyperplastic adrenals secrete androgens Gonadal Dysfunction Gonads fail to develop properly Gonadal Dysgenesis Swyer’s syndrome 46,XX Mixed Gonadal Dysgenesis 45,X/46,XY Primary Hypogonadism Affected females 46,XX Primary Hypogonadism Defective anterior pituitary production of gonadotropin Lack of gonadotropin-releasing hormone Tract Abnormalities Many different forms Uterine Associated with other anomalies Paramesonephric duct (0.1-0.5% of women) several classifications Unicornuate, bicornuate uterus Vagina Agenesis, atresia See also endocrine disruptors http://embryology.med.unsw.edu.au/Notes/endocrine2.htm Ductus Deferens Uni- or bilateral absence Failure of mesonephric duct to differentiate External Genitalia Multi-factoral Chromosomal, single gene, environmental Developmental arrest gives ambiguous Hypospadias Common male (1 in 300) failure of urogenital folds to fuse results in a proximally displaced urethral meatus Gonadal Descent Cryptorchidism One or both testes fail to descend into scrotum 1:30 live male births May be associated with other abnormalities Undescended Ovaries reasonably rare, also be associated with other uterine malformations (unicornuate uterus) Virilization of a Genetic Female with Ovaries Fetal androgens congenital adrenal hyperplasia (CAH) adrenal adenoma or hyperplasia Maternal androgens ovarian or adrenal tumors Latrogenic exogenous androgens or progestagens with androgenic activity Androgen Insensitivity Syndrome XY karyotype and presence of testes Externally develop female secondary sex characteristics Internally women lack Müllerian duct derivatives have undescended testes Sex and Brain Differentiation Brains of males and females differ regions specialized for reproduction Also in other regions (controlling cognition, etc) where sex differences are not necessarily expected Differentially susceptible to neurological and psychiatric disease 2 sources of sexually dimorphic information complement of sex chromosome genes mix of gonadal hormones sex differences in brain attributed to differential action of gonadal hormones evidence for sex chromosome effects on both neural and non-neural systems XX and XY cells differentiate even before they are influenced by gonadal hormones even if exposed to similar levels of gonadal steroids Hormone Axis - Reproduction Infections Infections