applied embryology Flashcards
What are the pre-requisits for a pregnancy to occur
functioning gametes - viable sperm and mature egg
patent reproductive pathway - vagina, cervix, uterus and fallopian tubes
release of the egg for fertilisation
ovulation - can survive for 1 day once released
picked up by the fimbrial end of the fallopian tube where it waits to meet the sperm
sperm reaching the egg for fertilisation
sperm released into the vagina
has to travel up through the cervix, uterine canal and fallopian tube to reach the egg in order to fertilise it
what happens during fertilisation
sperm enters the egg and unites with its nucleus
what follows fertilisation
organised series of cell division
cell numbers increase and form an early blastocysts ~day 5
embryo then implants into the womb
what is the outer layer surrounding the egg called
zona pellucida
what helps the sperm get into the egg
cap on the sperm head (acrosome) releases hydrolytic enzymes
helps it dissolve the zona pellucida and fet into the perivitelline space
what is the perivitelline space
the space between the egg and the zona pelludica
what occurs in the perivitelline space during fertilisation
sperm binds to the protein receptos an the plasma membrane of the egg and sperm fuse
sperm then releases its nucleus whih enters the egg
what happens once a sperm has released its nucleus into the egg
cortical reaction - egg plasma membrane becomes a tough wall and doesn’t let any more sperm in
what happens if multiple sperm enter the egg
abnormal fertilisation
these eggs aren’t capable of further cell division or pregnancy
what is the first stage in the egg following fertilisation called
pronuclei stage
2 nuclei in the fertilised egg (1 from egg and 1 from sperm)
what stages occur during day 1-5 following fertilisation
day 1 - pronuclei forms 2 - 1st cell division 3 - cell division continues 4 - formation of Morula 5 - blastocyst forms
what is a morula
cells continue to divide and numbers increase rapidly until you cannot count them but they form into a ball of cells - morula
this then organises into a blastocyst embryo
organisation of cells in the blastocyst
2 cell groups:
outer layer - trophoblast, placenta forms from this
inner layer - inner cell mass, this is where the embryo develops
what layer of the blastocyst invades the maternal endometrium
trophoblast
what are the 4 steps for implantation to occur
hatching
apposition
adhesion
invation
what is hatching
blastocyst has to come out of the zona
trophoectoderm cells produce protease to dissolve the zona in preparation for implantation
what is apposition
first connection between blastocyst and endometrium
apposes to microvilli like structure (pinopodes) expressed on receptive endometrium
how does the maternal endometrium become receptive
under hormonal preparation which happens in every monthly cycle
what is adhesion
earliest implantation sign
trophoblast of the blastocyst adheres to the epithelial layer of the maternal endometrium
embyronic tissue starts to actively secrete hCG
what is invasion
trophoblast proliferation and differentiation
crossing of the epithelial BM and invasion of endometrial stroma to form the placenta
uterine spiral arteries remodelled by the invasive trophoblast - placentation starts
what happens with inability to hatch
infertility
premature hatching can result in abnormal implantation in the uterine tube - ectopic
what regulates apposition and adherence
a number of growth factors and cytokines
this all has to happen in sync as well as with hormones for the implantation to happen
decidualisation prior to invasion
pre-requisite for trophoblast invasion and placentation
involves transformation of stromal cells of maternal endometrium every month under the effect of progesterone
what changes occur to the endometrium under the effect of progesterone prior to invasion
stromal cell differentiation - elongated fibroblast cells converted into decidual (rounded epithelial cells)
angiogenesis - increased vascular permeability
increased macrophages, lymphocytes and decidual leukocytes (uterine natural killer cells) for maternal immune tolerance
why are the changed in the endometrium important for invasion
transform the endometrium into a vascular receptive tissue for blastocyst invasion
describe placentation
invading trophoblast forms 1y chorionic villi
with infiltration of extra-embryonic mesoderm these become 2y villi
when capillaries form they become 3y villi
invasion of cytotrophoblast remodels spiral arteries to increase blood flow
what are the 2 cell layers of the trophoblast
inner part close to the inner cell mass = cytotrophoblast
outer part = syncytiotrophoblast
these are the parts which will develop into villi
placentation - what is the main function of villi
establish the connection with the maternal circuation
what is the mature placenta formed from
chorionic villi
intervillous space
placental septae
cotyledons - subunits of the placenta
what are the functions of the placenta
immunological barrier gas exchange nutrient exchange waste excretion endocrine functions - secreted hCG
what is embryogenesis
first 8wks of embyro development post-fertilisation
embryoblast development
wk2-3 - formation of bilaminar disc and development of amniotic sac, yolk sac, extraembryonic mesoderm and chorionic cavity
wk3-4 - differentiation of bilaminar disc into trilaminar structure - 3 germ layers (endoderm, mesoderm, ectoderm), through gastrulation and neural tube formation
wk5-8 - organogenesis
what are the different parts of the blastocyst and what are the cell types
inner cell mass (embryoblast) - pluripotent cells
bilaminar disc - epiblast (undergoes gastrulation) and hypoblast (forms extraembryonic mesoderm)
blastocele - fluid filled cavity
inner layer cytotrophoblast forms chorionic villi
inner cell mass differentiation
inner cell mass differentiates into bilaminar epiblast (columnar epithelial cells) and hypoblast
2 cavities form - yolk sac on side of hypoblast and amniotic cavity on side of epiblast
epiblast differentiation/gastulation
3 germ layers form - ectoderm, mesoderm, endoderm (day 13-16)
gastrulation starts with a groove appearing in the caudal end of epiblast (primitive streak)
newly formed trilaminar disc w/ 3 layers is called gastrula and forms the different organ systems
how is the endoderm formed
epiblast cells migrate into the hypoblast layer displacing them
how is the mesoderm formed
further epiblast cells migrate through primitive streak between the epiblast and the hypoplast/endoderm to form the mesoderm
how is the ectoderm formed
remaining epiblast becomes the ectoderm
what forms from the ectoderm
epidermis CNS PNS hair and nails neuroendocrine organs (adrenal medulla, pituitary) enamel of teeth
what forms from the mesoderm
dermis MSK structures CVS kidneys ureters trigone of bladder gonads (not germ cells) adrenal cortex visceral and parietal linings (pleura, pericardium, peritoneum)
what forms from the endoderm
lining of GI tract parenchyma of liver pancreas thyroid parathyroid tonsils and thymus bladder (not trigone)
what are the 3 major subunits of the mesoderm
paraxial - forms MSK structures
intermediate - forms kidney, ureter and gonads
lateral plate
what is a dizygotic pregnancy
≥2 eggs fertilising and implanting
non-idential
what is a monozygotic pregnancy
1 embryo splitting
timing of embryo splitting determines nature of pregnancy
identical twins
what type of twins are more common
non-identical
what is the risk of multiple pregnancy
natural conception - 1-2%
fertility treatments have increased the rates, target to keep <10%
DCDA twins
division day 1-4 post fertilisation
20%
MCDA twins
division day 5-8 post fertilisation
75%
seen in fertility treatment
MCMA twins
division day 7-14 post-fertilisation
5%
high risk twins - shared placenta, higher incidence of fetal death
conjoined twins
division >14 days post fertilisation
<1%
how is the urinary system linked to the gonads
kidney and ureter and repro system develop from the urogenital ridge in the intermediate mesoderm (same origin)
urogenital ridge differentiates into gonadal ridge medially which gives rise to gonad and nephrogenic cord laterally (forms kidney and ureter)
urinary system develops ahead of repro system from wk4
development of urinary system
kidney, ureter, bladder and urethra
kidney and ureter develop from 3 overlapping system in nephrogenic cord portion of urogenital ridge (pronephros, mesonephros and metanephros)
kidney develop in pelvis and then ascend into abdo with final position by wk12
bladder and urethra formed from urogenital sinus (part of cloaca) which also gives rise to parts of female and male repro tract
what are the 3 stages of development of the kidneys and ureter
pronephros - non-functional
mesonephros - functional but transient
metanephros - kidneys
where does the kidney form from
metanephric mesenchyme
what forms the ureter
ureteric duct
what is the cloaca
common temporary outlet for digestive, urinary and genital tract in embryonic life
nephric duct drains into this
what is the nephric duct
connects pronephros, mesonephros and metanephros
what are 6 examples of renal anomalies
renal agenesis horseshoe kidney pelvic kidney duplex kidney duplex ureter and calyceal system
what is renal agenesis
no kidney
one of the metanephric ducts or none develop
gives rise to a unilateral kidney system
complete renal agenesis = no kidney
what is a pelvic kidney
kidneys have failed to ascend from the pelvis to the abdomen
what is a horseshoe kidney
fusion of the kidneys during ascent
get stuck so cannot ascend any further
where is the cloaca located and what are its coverings
caudal end of the enfolded yolk sac
covered in cloacal membrane which is formed by the fusion of the ectoderm and endoderm
what does the urorectal septum form
cloaca is divided by the urorectal septum to form:
urogenital sinus
anal canal
what does the urogenital sinus form
bladder and urethra
what forms the trigone of the bladder
mesonephric duct below the ureteric bud is incorporated into the bladder as the trigone
where does the indifferent gonad develop
in the gonadal ridge
what is the gonadal ridge related to
closely related to the mesonephros
where do the primordial germ cells originate from
do not originate in the gonadal ridge
they migrate to the gonads from the endoderm lining of the yolk sac via the hindgut at wk6
what forms the primitive sex cords
epithelium of gonadal ridge
what forms the indifferent gonad
combination of germ cells and primitive sex cords
indifferent gonad is capable of developing into a testis/ovary
what determines whether the indifferent gonad becomes a testis/ovary
Y chromosome contains SRY gene
SRY produces testis determining factor
protein acts on the indifferent gonad to promote the formation of the testis
in rare cases following a translocation error, a male can be born w/ 46 XX karyotype
development of the ovary
migrating germ cells enter the ovary
primitive sex cords extends into the medulla but degenerate
2y sex cords (cortical cords) develop and surround the germ cells –> ovarian primordial follicles
ovarian follicle pool established at 20wks gestation
development of the testis
migrating germ cells enter the testis
primitive sex cords extend into medulla and forms testis cords which transform into future seminiferous tubules and rete testis
sertoli cells are derived from surface epithelium under effect of AMH
Leydig cells are produced from intermediate mesoderm and produce testosterone from wk8 onwards
where do the testis develop
posterior abdo wall and then descend through the deep inguinal ring ~7mths into the scrotal sac
why do the testis have to descend
scrotal sac temp is lower than body temp
required for proper spermatogenesis
what % have undescended testis
2-3%
can be in the abdo area or somewhere in the inguinal canal
what is cryptochordism
when is it checked for
what is the management
undescended testis
checked for in all male infants
early corrective surgery to prevent effects on fertility later on
what is cryptochordism
when is it checked for
what is the management
undescended testis
checked for in all male infants
early corrective surgery to prevent effects on fertility later on
what are the 2 sets of genital ducts
mesonephric duct next to the gonad
paramesonephric duct laterally
what is AMH and why is it important
Anti-Mullerian hormone
presence/abscence determines which of the genital ducts develops and which regresses
males - presence of AMH causes paramesonephric ducts to regress and these don’t form any part of the adult
where do the mesonephric duct and paramesonephric duct open into
urogenital sinus
which ducts remain in males and females
Mesonephric - Male
paramesonephric - female
what do the mesonephric ducts drian
aka Wolffian ducts
drain mesonephros into the cloaca
what does the mesonephric duct form
in both males and females it forms the trigone part of the bladder?
persistence of mesonephric duct in males
persists under the effect of testosterone
forms epididyms, vas deferens and seminal vesicles
regression of mesonephric duct in females
remnants might remain as epophoron, paraophoron (small cysitc structures lateral to ovary) and gartners duct cyst
what is gartner’s duct cyst
benign lesions on lateral vaginal wall
female reproductive tract development
absence of AMH
paramesonephric ducts continue to develop, mesonephric ducts regress
paramesonephric ducts grow medially and fuse - fused portions canalises to form uterus and upper 2/3 of vagina
unfused portions give rise to fallopian tubes
paramesonephric ducts fuse w/ urogenital sinus at the sinus tubercle, point of fusion –> hymen
what forms the lower 1/3 of the vagina
urogenital sinus
development of external genitalia
on either side of the cloacal membrane folds develop - urogenital folds
these fuse anteriorly –> genital tubercle
lateral to this are the labioscrotal swellings
as the cloaca is split by the urorectal septum the anus is separated off
male external genitalia development
genital tubercle elongates to form the penis
labioscrotal swelling folds fuse posteriorly - form scrotum
urogenital folds fuse posterior to anteriorly to form penile urethra (spongy urethra)
glans penis will canulate at the tip to form the final part of the urethra
female external genitalia
urogenital folds form labia minora
labioscrotal folds form labia majora
genital tubercle forms clitoris
male repro tract anomalies
penile - micropenis, hypospadia
testicular - absence, undescended (cryptochordism)
absence of vas deferens - CF
absence of seminal vesicles
how does a micropenis occur
tubercle doesn’t elongate fully
what is hypospadias
development problem causing urethral opening to be abnormally located e.g. undersurface of penis
female repro tract anomalies
common - 4-7%
no one agreed classification system (ASRM, ESHRE/ESGE)
association w/ renal tract anomalies
uterine
vaginal
MKRH syndrome
uterine anomalies
underdevelopment - uterine agenesis, unocornuate uterus
fusion - didelphys uterus, bicornuate
resorption - septate uterus, arcuate uterus
how do uterine anomalies occur
paramesonephric ducts on one or either side don’t develop properly - agenesis or unicornuate
ducts don’t fuse correctly in the middle (no fusion - didelphys, part fusion - bicornuate)
fused part of ducts doesn’t undergo canalisation, remains as fibromuscular band (uterine septum), septation can be partial or complete
vaginal anomalies
vaginal septa - longitudinal or transverse
imperforate hymen
vaginal agenesis - absent or underdeveloped uterus and vagina
MKRH syndrome
Mayer Rokitansky Küster Hause
aka Mulleria agenesis syndrome
failure of paramesonephric ducts to develop normally - absence of all female repro tract
