Nineteen Flashcards
(20 cards)
When is genetic sex determined? How long are the gonads undifferentiated? What determines differentiation? Another name?
The fetus’ chromosomal or genetic sex is
determined at the time of fertilization
Gonads undifferentiated until 7 weeks
Gonadal differentiation determined by SRY
(sex-determining region on Y) on short arm
of Y chromosome
The SRY protein is testis-determining factor
(TDF) gene
If no Y chromosome present, default
differentiation is to an ovary
Describe the development of sex cords in males. Describe the tubule system from testis to urethra.
If primordial germ cells are XY, TDF signals
continued proliferation and penetration of
primitive sex cords deep into the medulla–>
testis or medullary cords. Thick tunica albuginea develops around cords.
Medullary cords connect to rete testis which connect to efferent ductules—>epididymis–>ductus deferens—>urethra (this occurs in prostate and right before the seminal vesicle connects with the tubule).
Describe the development of sex cords in females.
Without TDF from Y chromosome, primitive
sex cords broken up into irregular clusters
containing groups of primitive germ cells
Primitive sex cords or medulary cords
disappear and are replaced by a vascular
stroma to form the ovarian medulla
Cortical cords develop.
Of what origin are female ducts? Male?
All embyros start out with mesonephric and
paramesonephric ducts
Paramesonephric = female ducts
(Mullerian)
Mesonephric = male ducts
(Wolffian)
Describe the differentiation of male ducts, including the tubule system from testis to urethra. Describe the development of male glands.
SRY upregulates production of
steroidogenesis factor 1 (SF1) that stimulates
differentiation of Sertoli and Leydig cells
Sertoli cells in the male gonad begin making
mullerian inhibiting factor (MIF), causing
regression of the paramesonephric ducts
Leydig cells begin making testosterone ~ 9
weeks
Testosterone binds to androgen receptors in
mesonephric ducts to stimulate their continued
growth
Main portion of the mesonephric duct acquires
smooth muscle to become the ductus deferens
Mesonephric ducts also form the epididymis and
efferent ductules which join the rete testis of the
gonad
Androgens influence mesenchymal cells at the
urethra to interact with nearby epithelium to
differentiate into male glands (prostate and
seminal vesicles)
Describe the differentiation of female ducts.
If no Y chromosome, then no Sertoli cells
produce MIF and no Leydig cells produce
testosterone
Paramesophric ducts continue to grow because
no MIF
Mesonephric ducts regress because no
stimulation from testosterone
Both paramesonephric ducts develop into the fallopian tubes with fimbriae. At the caudal section, the two ducts fuse and uterine septum eventually dissociates forming the lumen of the uterus. The tips of the ducts bind to the urogenital sinus and the sinovaginal bulbs. The sinovaginal bulbs form the caudal 2/3 of the vagina and the paramesonephric ducts form the rostral 1/3 and the cervix.
Describe the parts of the differentiation of the external genitalia that are shared.
Undifferentiated until 6 weeks gestation
At 3 weeks, mesenchyme cells from the
primitive streak migrate around cloacal
membrane to form a pair of cloacal folds
These folds fuse to form the genital tubercle
At 6 weeks, cloacal membrane divides into
urogenital and anal membranes, and the cloacal
folds become urethral folds and anal folds
A second pair of swellings forms lateral to the
urethral folds to form genital swellings which
develop into scrotum or labia majora
Describe the differentiation to male external genitalia.
Testosterone made by the Leydig cells is
converted to dihydrotesoterone (DHT) by an
enzyme (5 a reductase) which stimulates rapid
growth and elongation of the genital tubercle to
form the penis
The urethral folds get pulled forward and closer
to each other and eventually fuse (penile urethra)
Genital swellings migrate caudally and fuse to
become the scrotal sacs
Describe the differentiation to female external genitalia.
Default development of the external genitalia is to
female structures if no DHT can be recognized by
the appropriate cells
Minimal growth in the genital tubercle (clitoris)
Urethral folds remain unfused (labia minora)
Genital swellings do not fuse (labia majora)
Open urogenital sinus remains as a cleft
(vestibule)
What is kleinfelter syndrome? How is it characterized? Caused?
Kleinfelter syndrome
47 XXY
Characterized by infertility, gynecomastia,
varying degrees of impaired sexual maturation
Nondisjunction of the XX homologues is the
most common causative factor
What is Turners syndrome? Describe the pathogenesis. How is it characterized?
Gonadal dysgenesis or Turner’s syndrome
45 X
Primordial germ cells migrate to undifferentiated
gonad but few if any follicles develop and germ cells
degenerate
Placental and maternal estrogens stimulate
paramesonephric duct development
No Y chromosome = regression of mesonephric
ducts and no testosterone effect on external
genitalia
Normal external genitalia with uterus but absent
breasts
Amenorrhea due to streak ovaries
Short stature, webbing of the neck, coarctation
of the aorta, shield chest with widely spaced
nipples
Associated with renal anomalies, especially
horseshoe kidney
What is pure gonadal dysgenesis? Pathogenesis?
Pure gonadal dysgenesis
46 XX or 46 XY (normal karyotype)
Primordial germ cells do not develop or migrate
into genital ridge and therefore, no gonad develops
No testosterone, no MIF–>mesonephric ducts
regress and female external genitalia
Placental and maternal estrogens stimulate
paramesonephric duct development
What is a true hermaphrodite? How is it characterized? What does the phenotype depend on?
True hermaphrodite
Gonads of both sexes are present so that
patient has both active testicular and ovarian
tissue
Phenotype depends on relative contribution
of each
What causes the following? How are they characterized?
Unicornuate uterus
Bicornuate uterus
Uterus didelphys
Uterine septum
Longitudinal vaginal septum
Transverse vaginal septum
Paramesonephric anomalies from lack of fusion
of the paramesonephric ducts
Unicornuate uterus-uterus formed from only one duct
Bicornuate uterus-Uterine septum fails to be resorbed. Failure of fusion. Caudal part unitary, rostral separate”Heart shaped”
Uterus didelphys-Ducts fail to fuse—>two uteruses possibly with 2 cervices
Uterine septum-failure of resorption
Longitudinal vaginal septum
Transverse vaginal septum
What is a gartners duct cyst? What is a cyst of morgagni?
Persistence of caudal portion of mesonephric
ducts leads to lateral vaginal wall cyst =
Gartner’s duct cyst
Persistence of cephalad portion leads to cyst of
Morgagni = paratubal cyst
Describe the two pathogeneses of abnormal genitalia? Causes ?
Ambiguous genitalia
Either XY with some resistance to normal
virilization (partial androgen insensitivity
syndrome with defective androgen receptors)
Or XX with exposure to elevated levels of
androgens during fetal life or later (congenital
adrenal hyperplasia, maternal ingestion of
androgens)
What is androgen insensitivity syndrome? What is the pathogenesis? How is it characterized?
Androgen insensitivity syndrome
Karyotype XY but defective testosterone
receptors in tissues
Gonads are testes and make testosterone and
MIF
MIF causes paramesonephric ducts regress
Testosterone cannot stimulate external genitalia
to develop into penis or stimulate development
of mesonephric ducts since the receptor is
defective
Phenotype – normal female
Normal external female genitalia, minimal
body hair, primitive or absent paramesonephric
structures (eg. no uterus), female breasts
What is hypospadias? Epispadias? Bladder exstrophy?
Hypospadias
Abnormal opening of the urethra along the
ventral (inferior) aspect of the penis due to
incomplete fusion of the urethral folds
Epispadias
Urethral meatus is on the dorsal aspect of the
penis
Bladder exstrophy
Bladder mucosa is exposed on the outside and
features epispdias
Describe the descent of the gonads.
Mass of undifferentiated mesenchymal cells
develops on either side of vertebral column
(gubernaculum)
Cephalad end attaches to lower poles of
developing gonads
Caudal end moves through inguinal canal and
attaches to genital swellings
Swelling of the cephalad portion of the
gubernaculum enlarges the inguinal ring and
the peritoneum descends into the ring (process
vaginalis)
Process vaginalis is then resorbed leaving only the tunica vaginalis behind.
Describe how a congenital inguinal hernia can occur? A hydrocele?
With no obliteration of the processus
vaginalis, congenital inguinal hernia can
develop
With irregular obliteration of the processus
vaginalis, cysts can form in the inguinal
canal and may secrete serous fluid causing a
hydrocele
