B8.002 Development of the Reproductive System Flashcards
conditions with gonadal failure
klinefelters (XXY)
turner (XO)
triple X females (XXX)
gonadal migration failures
hydrocele
cryptorchidism
congenital inguinal hernia
mullerian duct defects
abnormal uterine forms
penile defects
hypospadias
epispadias
disorders of sexual development
ambiguous external genitalia
congenital adrenal hyperplasia (females)
androgen insensitivity syndrome (males)
5 alpha reductase deficiency (males)
for the first 6 weeks of human life…
no known phenotypic difference between males and females
genetic sex
determined at fertilization/conception by the sperm
gonadal sex
determined at about the 6th embryonic week when a bipotential gonad is induced to form either a testis by the SRY gene (on Y chromosome) or an ovary
phenotypic sex
determined from the 7th embryonic week through birth and on to puberty
full differential requires proper hormone function
psychological sex
imprinting and learning of sexual behavior
timing likely parallels behind phenotypic sexual development and both gender identity and sexual preference occur over a lifetime
components of psychological sex
- gender identity
- gender roles
- gender orientation, the choice of sex partners
what determines sex?
SPERM
can be X or Y
eggs can only be X
X chromosome genes
essential for human life
2000 genes
one X randomly and permanently inactivated in females
just another reason that i don’t understand why historically men are regarded as the superior sex like we literally don’t even need their stupid DNA to survive but its fine its fine i wonder if we could take 2 X eggs and mush them together and eliminate the need for sperm altogether? like why are they even necessary
turner syndrome
X sperm + O egg
gonadal dysgenesis
95% of infants are spontaneously aborted in the 1st trimester
triple X syndrome
X sperm + XX egg
phenotypically normal
lethal abnormal meiotic event
Y sperm + O egg
klinefelters
Y sperm + XX egg
extra X inhibits testis development
seminiferous tubule dysgenesis
Y chromosome genes
60 genes
23 proteins
holandric traits
extra X chromosome
whether in males or females, often associated with an increased risk of learning disabilities and delayed development of speech and language skills
phenotypes of XXX females
may be taller than normal
may produce normal offspring
delayed development of motor skills, weak muscle tone, and behavioral and emotional difficulties are possible, but vary widely among those affected
premature ovarian failure (< 40) is common
90% NOT DIAGNOSED AS THEY HAVE NO OR FEW SYMPTOMS
klinefelters phenotype
small to normal penis small testicles (spermatogenesis not functional when extra X is present in germ line)
turner syndrome phenotype
half have puffy hands and feet at birth in addition to wideness and webbing of neck (50% diagnosed at birth)
adults: infertility, short stature, lymphedema, webbed skin behind neck, low airline, widely spaced nipples, small breasts, brown spots, small finger nails, horseshoe kidney (15%), ovarian failure
normal puberty doesn’t occur without hormone therapy
NORMAL INTELLIGENCE
cardio effects of turner
coarctation of the aorta (1 in 15)
bicuspid aortic valve
aortic dissection in adulthood
risks of egg donation in turner
only 40% of pregnancies normal
high risk endeavor
male genetic signals
SRY
SOX9
SF1
female genetic signals
WNT4
DAX1
TAFII 105
3 cell types from which the gonads develop
- coelomic (future peritoneal cavity lining)
- underlying mesenchyme from intermediate mesoderm (mesonephros)
- primordial germ cells which migrate from the yolk sac
origin of wolffian duct
mesonephric duct (2nd kidney stage)
origin of mullerian duct
paramesonephric duct
develops as an invagination of the coelomic epithelium
why oviducts are open to the peritoneal cavity
oogonia
primordial germ cells within the developing ovary
10% of cells within the ovary by weeks 7-9
divide mitotically
follicular cell origin
mesenchymal cells surround oogonia and become follicular cells
enter a protracted stage of meiosis
oocytes
female germ cell in meiosis
primordial follicles
oocytes surrounded by flattened follicular cells
first seen at week 14
what happens if an oocyte isnt surrounded by follicular cells?
apoptosis
steroid influence on ovarian development
little steroid production by fetal ovary
is NOT necessary for development of female tubular/ductal structures or female external genitalia
3 step overview of ovarian development
- ovarian development lags slightly behind testicular development
- cortical sex cords differentiate into follicular cells and incorporate primordial germ cells, which will subsequently form oogonia. surrounding follicular cells inhibit completion of meiosis until puberty
- clusters of follicular cells surround the central oogonium and inhibit female germ cells in the first meiotic division
primordial germ cells that enter the gonad at 6th week
1,300
oocytes at 20th week
300,000
oocytes at birth
295,000
oocytes at puberty
180,000
ovulated eggs during reproductive years
500
oocytes at menopause
0
importance of AMH levels
anti mullerian hormone
expressed in granulosa cells of growing follicles
expression highest in preantral and small antral follicles
levels decrease with age in premenopausal women
levels correlate strongly with # of antral follicles, aka they can reflect the size of your primordial follicle pool
relationship between genital system and urinary system
close conjunction
male accessory repro organs develop from embryonic urinary system structures
inherent phenotype
FEMALE
THE FUTURE IS FEMALE
#FEMINISM
function of AMH in males
suppresses female structures
comes from testicular sertoli cells
what does the paramesonephric (mullerian) duct form in females
oviducts
uterus
upper 1/5 of vagina
outline the development of the non gonadal female reproductive organs
caudal ends of paramesonephric ducts grow together as they join the urogenital sinus, forming a joint midline structure, the uterovaginal primordium
uterovaginal primordium forms 1/5 of the vagina and the cervix and uterus
where the uterovaginal primordium meets the urogenital sinus, it induces the sinusal tubercle forming the distal 4/5 of the vagina
discuss the presence of vestigial structures formed from urogenital ducts
in both males and females, remnant of embryonic urogenital structures can be present and cause little or no harm
female remnant of mesonephric ducts that did not undergo complete apoptosis
- paroophoron
- epoophoron
- duct of Gartner
male remnants of paramesonephric ducts
appendix of the testis
prevalence of congenital uterine anomalies
5% of women
10% of women with recurrent pregnancy loss
examples of congenital uterine abnormalities
midline septum (septate uterus) Y shaped (bicornate uterus) one horn (unicornate uterus) double uterus (didelphys)
midline septum problems
reduced fertility levels and 1st trimester loss
bicornate/unicornate uterus problems
low birth size and premature delivery
cloaca
expansion of rectum separated into: 1. urogenital sinus 2. rectum separated by formation of 3 folds (collectively the urorectal septum) 1. superior Tourneux 2. L and R Rathkes
subdivision of urogenital sinus in females
- sinovaginal bulbs: form distal 4/5 of vagina from sinusal tubercle
- urethra and bladder
why should you check newborns for the presence of an anus?
may have:
- rectoprostatic urethral fistula
- rectocloacal canal
- rectovaginal fistula
how is the broad ligament formed
fusion of paramesonephric ducts from each side bringing together peritoneal folds
ovaries located on posterior surface
vesicouterine pouch
anterior to uterus
rectouterine pouch
posterior to uterus
function of the broad ligament
supports the uterus in the midline
overview of development of the testis
primordial germ cells (gonocytes) migrate into the gonadal ridge
mesenchymal cells surround PGCs and differentiate into sertoli cells
this combo forms sex cords, the precursors to seminiferous tubules
mesenchymal cells also differentiate into interstitial Leydig cells between developing sex cords
function of embryonic sertoli cells
produce AMH
prevents femal reproductive structures from forming from the mullerian ducts by inducing apoptosis
function of embryonic leydig cells
produce testosterone
induces male reproductive structure differentiation from the mesonephric duct structures (rescuing them from spontaneous apoptosis in normal females)
function of dihydrotestosterone in embryonic testis
external genitalia formation
more potent than regular testosterone
structures derived from the mesonephric (wolffian) duct
epididymis
vas deferens
ejaculatory duct
seminal vesicle
origin of prostate gland
develops from invagination of prostatic urethra (urogenital sinus endoderm)
describe the differential migration of growing mesonephric ducts and ureter
mesonephric ducts continue to migrate inferiorly, ending up opening within the prostatic urethra, inferior to the bladder into the urethra
future vas deferens opens through the prostate gland into the urethra
two ligaments involved in descent of gonads
- superior suspensory ligament
2. gubernaculum
describe the gubernaculum
extends from inferior pole of the gonad through the inguinal canal into the labioscrotal swellings
does not contain muscle, but rather a band of mesenchymal tissue
“pulling” = lack of growth while the embryo gets bigger
processus vaginalis
extension of peritoneum
hernaties through the abdominal wall just anterior to the path of the gubernaculum
carries layers of the extensions of the abdominal wall that will form the layers of the inguinal canal and in males the coverings of the spermatic cord and testis
final descent of testis into scrotum
mediated by T and insulin like growth factor 3 from leydig cells
hiccups or uterine contractions help push testes
deep inguinal ring
opening in transversalis fascia
superficial inguinal ring
opening in external oblique aponeurosis
when do the testes migrate to the deep inguinal ring?
7th month
takes about 4-5 days to get through inguinal canal
locations of cryptorchid testes
not all the way descended at birth 62% are within the inguinal canal 26% within abdominal cavity 8% at deep inguinal ring 4% at superficial inguinal ring
orchioplexy
placing testicle into scrotum
should be performed prior to 1 year of age for maximal changes of fertility
if child reaches 10, remove testicle due to cancer risk
cryptorchidism
failure of full descent of testes into scrotum
2-3% of full term newborns
hydrocele
persistent processus vaginalis large enough to only permit passage of peritoneal fluid
1-2% of newborn males
normally resolve in a few months
congenital inguinal hernia
persistent processus vaginalis that allows herniation of intestine into scrotum
1-2% of baby boys
spontaneously resolve by 2 years in some cases
layers in adult scrotum
from outer to inner
- external abdominal oblique»_space;>external spermatic fascia
- internal abdominal oblique»_space;> cremasteric fascia and muscle
- transversus abdominus (doesn’t contribute to scrotum)
- transversalis fascia»_space;> internal spermatic fascia
descent of the ovaries
gubernaculum guides ovaries into the pelvis and forms the proper ligament of the ovary and round ligament of the uterus
female hydrocele
fluid collection along the canal of nuck (around round ligament of the uterus as it passes through the anterior abdominal wall into the labia majora)
4 common embryonic structures to external genitalia of both sexes
genital tubercle
urogenital folds
urethral groove
labioscrotal swelling
genital tubercle derivative
female: clitoris
male: penis (glans)
urogenital fold derivatives
female: labia minora
male: penis body/shaft
urogenital groos derivatives
female: opening of urethra and vagina
male: opening of urethra
labioscrotal swelling derivatives
female: labia majora
male: scrotal wall
hypospadia
failure of fusion of the urogenital fold to meet in a midline
opening of the urethra on the ventral surface of the penis or scrotum
1 in 125 male births
epispadia
opening on the dorsal surface of the penis
more unusual than hypospadia
1 in 30,000 males
should you circumcise boys w hypo/epispadias?
no
need foreskin for repair
how are hypospadias classified
location of the meatus
what is a disorder of sex development (DSD)
discrepancy between external and internal genitals
“hermaphrodite”
true hermaphrodism
individual born with ovarian and testicular tissue
extremely rare
pseudohermaphroditism
child is born with external genitalia that doesn’t match the expected gonadal tissue present
DSD
46, XX intersex
chromosomes of a woman, ovaries of a woman, but external genitals that appear male
female fetus exposed to excess males before birth
causes of 46, XX intersex
congenital adrenal hyperplasia (most common)
male hormones taken or encountered by mother during pregnancy
testosterone producing tumor (often ovarian) in mother
pathogenesis of congenital adrenal hyperplasia
defects in cortisol pathway in adrenal results in excess production of ACTH hormones and an excessive stimulation of adrenal fetal cortex
this leads to androgen production which tends to masculinize the external genitalia of genetic females
**male infants have no unusual phenotpe
1 in 15,000
genetics of CAH
autosomal recessive
95% of the time due to defective 21 hydroxylase which causes reduced aldosterone and cortisol and excess levels of adrenal androgens
other symptoms of CAH (not related to genitalia)
high rate of sodium loss in urine (due to lack of aldosterone) > dehydration hyperkalemia metabolic acidosis cortisol deficiency poor weight gain vomiting
fate of children with CAH
vomiting, severe dehydration, and circulatory collapse by 2-3rd week of life
treatment of CAH
mineralocorticoids
karyotyping to determine sex
generally females are not surgically altered until female grows old enough to participate in decision making
46, XY intersex
chromosomes of a man
external genitals incompletely formed, ambiguous, or female
internal testes may be normal, malformed, or absent
causes of 46, XY intersex
problems with testes (not producing hormones) problems with T receptor problems with T formation AIS
androgen insensitivity syndrome
most common cause of 46, XY intersex
hormones are normal, but receptors to male hormones dont function properly
over 150 different defects in androgen receptor have been identified
phenotypic females, no internal structures (no androgen function to create male structures, but AMH still present to inhibit female structure)
appearance of individuals with 5-alpha reductase deficiency
cause of 46, XY intersex
can have either normal male external genitalia, ambiguous genitalia,or normal female genitalia
have internal male structures but usually have female external genitalia
often raised as girls
function of 5-ARD
converts T > DHT
DHT helps masculinize external genitalia
puberty in 5-ARD deficient individuals
some individuals experience masculinization
approx 60% choose to then live as males
