Early fetal development

Question 1

how can time spent in embryo-fetal development be measured

Answer 1

3 different methods:

fertilization age

gestational age

carnegie stage

Question 2

what is fertilisation age

how is it measured

Answer 2

the number of days/weeks that have passed since fertilization occured

it is difficult to know the exact date on fertilisation when conceiving using natural methods (i.e. not IVF)

therefore the date of fertilisation is inferred as being 1 day after ovulation occured (as fertilisation must occur within 24 hrs of ovulation, ovulation date will be 14 days after the start of the period menses bleeding)

(not very useful measure practically)

Question 3

what is gestational age

how is it measured

Answer 3

number of days/weeks that have passed since the start of the last menstrual period

can be determined in 3 ways:
if woman knows date of last period (when bleeding first started) - will be number of days since then
or can minus 14 days from the fertilization date
or can do early obstetric ultrasound and compare embryo to size charts

Question 4

what is the difference between gestational and fertilisation age

Answer 4

both measure time spent in embryo-fetal development

fertilisation age is always 14 days longer than gestational age

fertilisation age - time elapsed since fertilisation occurred

gestational age - time elapsed since start of last menstrual period

Question 5

what is carnegie stage

how is it measured

Answer 5

made up of 23 stages of embryonic development

measures embryo development based on features it has not time spent in utero (i.e. structures or features that are present or absent)

allows direct comparison of developmental rates and events between species

covers time period from fertilisation date to approx 60 days post fertilisation

Question 6

how is carnegie stage different from gestational age and fertilisation age

Answer 6

fertilisation and gestational age measure embryonic-fetal development based on time

carnegie stage measures embryonic-fetal development based on embryo features not time
also only covers time period from fertilisation date - 60 days post fertilisation

Question 7

how can pregnancy be divided according to embryological development

Answer 7

embryogenic stage: 14-16 days post-fertilization
first trimester

embryonic stage: 16-50 days post fertilization
first trimester

fetal stage: 50-270 days post fertilization (approx. 8-38 weeks)
second and third trimester

(each trimester is 12 weeks)

Question 8

what occurs in the embryogenic stage of fetal development

Answer 8

time period between fertilisation date to 14/16 days post fertilisation

early embryo being formed from fertilised oocyte

characterised by formation of 2 distinct cell types:
pluripotent embryonic cells - contribute to fetus
extraembryonic cells - contribute to support structures e.g. placenta

(1st trimester)

Question 9

what occurs in the embryonic stage of development

Answer 9

time period between 16-50 days post fertilization

establishment of germ layers

differentiation of tissue types

establishment of body plan

(still 1st trimester)

Question 10

what occurs in the fetal stage of development

Answer 10

50-270 days post fertilisation (approx 8-38 weeks)

major organ systems are now present

migration of some organ systems to their final location

extensive growth + acquisition of fetal viability - ability of fetus to survive outside womb

(2nd and 3rd trimesters)

Question 11

when does a fetus become an embryo

Answer 11

roughly at the end of 1st trimester

(transition from embryonic to fetal phase)

Question 12

describe the first few days of life

Answer 12

ovulation - oocyte released from ovary into fallopian tube

oocyte fertilised by sperm → zygote (made up of 1 cell)

zygote undergoes mitotic divisions → cleavage stage embryos (made up of 2 then 4 then 8 cells)

cleavage stage embryo undergo mitotic divisions → morula (made up of over 16 cells)

morula undergoes mitotic divisions → blastocyst (made up of over 200 cells)

all occurring whilst oocyte then early embryo is migrating along fallopian tube to uterus

zona pellucida remains intact throughout whole process → mitotic divisions are occurring within restrictions of zona pellucida

Question 13

label the stages of cell development in the first few days of life

Answer 13

note: intact zona pellucida

Question 14

what is the maternal to zygotic transition

when does it occur

what are its main features

Answer 14

it is when development control is transferred from mother to embryo
before the transition, no embryonic genes are transcribed, maternal mRNA and maternal proteins synthesised + stored during oocyte development (pre-ovulation) are responsible for allowing zygote to divide to form embryo (i.e. to go from 1 → 2 → 4 cells)

after the transition occurs the zygote’s genome is activated → its own genes are transcribed, therefore reliance on maternal mRNAs + proteins are lost, embryo undergoes increased protein synthesis + maturation of organelles - especially mitochondria and golgi (as they are involved in metabolism and protein synthesis + distribution)

occurs when the embryo is mitotically dividing from 4 to 8 cells (cleavage stage embryos period)

Question 15

what is the importance of maternal mRNAs and protein development before ovulation

Answer 15

very important

because embryo is reliant on the maternal mRNA and proteins to undergo its first few mitotic divisions (as none of its own genes are transcribed until the maternal to zygotic transition at the 4 to 8 cell stage)

so if these maternal mRNAs or proteins are not synthesised, stored or interpreted correctly during oogenesis → can lead to impaired embryonic developement

Question 16

when would the maternal to zygotic transition occur

what are the features associated with this

Answer 16

4 to 8 cell stage

Question 17

what is compaction

what are its main features

when does it occur

Answer 17

process which starts the formation of 2 distinct cell lineages

occurs around the 8 cell stage (then divides to form morula)

as more cells form due to mitosis the outer cells of embryo are pressed against the zona pellucida → change in shape from spherical to wedge-shaped

these outer cells then develop connections with each other through tight gap junctions + desmosomes → this means that there is a diffusion barrier between the inner and outer cells of embryo

outer cells also become polarised (apical + basal polarity)

2 distinct cell populations in embryo - inner and outer

Question 18

how do the cell populations formed in compaction contribute to further embryonic development

Answer 18

morula → blastocyst

following compaction the inner + outer cells reorganize themselves as cell division continues to allow formation of blastocoeal cavity (inner cells clump to form a mass together, outer cells become shell-like layer)

2 distinct populations

inner cells - pluripotent embryonic cells → contribute to fetus development

outer cells = trophectoderm - extra embryonic cells → contribute to extraembryonic structures which support development e.g. placenta

Question 19

what is the zona pellucida

what is its function

Answer 19

hard protein shell surrounding embryo

prevents polyspermy and protects early embryo

limits embryonic development by restricting size until hatching occurs

Question 20

how does blastocyst form

Answer 20

inner cells have formed a mass together (pluripotent embryonic cells)

trophoblasts (extra embryonic cells) which form outer layer actively pump Na+ ions into cavity

this creates osmotic potential for water to enter → fluid filled blastocoel cavity forms

(zona pellucida is still present)

Question 21

what is hatching

why is it necessary

Answer 21

necessary because zona pellucida limits the developmental potential of the embryo by limiting the size to which it can grow (i.e. number of cells which can form)

escape of blastocyst from zona pellucida shell - achieved through combination of enzymatic digestion + cellular contraction by embryo → weaken a point of zona pellucida which allows blastocyst to extrude itself out of the shell → implant in endometrium

blastocyst needs to hatch, otherwise it can’t implant in endometrium

Question 22

label this

Answer 22

Question 23

draw out process of pre-implantation development

Answer 23

Question 24

describe the cellular changes that occur in the peri-implantation period (7-9 days post fertilisation)

Answer 24

trophectoderm forms 2 cell lineages - syncytiotrophoblasts and cytotrophoblasts

syncytiotrophoblasts are invasive cells → invades endometrium by destroying maternal endometrial cells, ultimately degrades capillary endothelial cells → creates interface between embryo and maternal blood

cytotrophoblasts - continue to divide to provide a source of syncytiotrophoblasts

inner cell mass forms 2 cell lineages as well - hypoblasts and epiblasts

epiblasts - cells which the fetal organs + tissues will be derived from

hypoblasts - cells which will form the yolk sac (located on underside of epiblasts cells, facing cavity)

Question 25

label the cells what are the functions of each

Answer 25

Question 26

what allows the pregnancy to be detected on test

Answer 26

secretion of beta HcG by syncytiotrophoblasts which starts once embryo has implanted in endometrium and bi-laminar disc formed (around 12 days post fertilisation)

Question 27

describe the cellular changes that occur in peri-implantation period (12+ days post fertilisation)

Answer 27

syncytiotrophoblasts continue to invade maternal endometrium (cytotrophoblasts continue dividing to be a source of syncytiotrophoblasts) epiblasts become separated by formation of amniotic cavity: epiblasts above the amniotic cavity → form amnion → gives rise to extra embryonic structures epiblasts below the amniotic cavity and the layer of hypoblasts form bilayer embryonic disc formation of the bilayer embryonic disc signifies that the embryo is ready for gastrulation

Question 28

label the diagram what are the functions of the cells what is the significance of this

Answer 28

Question 29

draw flow diagram of the cell lineages that form during the transition from morula to blastocyst

Answer 29

Question 30

what is the bilaminar disc when does it form what is its significance

Answer 30

2 layers of cells - epiblast and hypoblasts formed around 12+ days post fertilisation when amniotic cavity forms and separates the epiblasts into 2 different populations formation of the disc signifies that embryo is ready for gastrulation

Question 31

what is gastrulation when does it occur

Answer 31

starts once bilaminar disc has formed (12+ days post fertilisation) and occurs in week 3 (post fertilisation) differentiation of the bilaminar disc into the 3 primary germ layers - endoderm, mesoderm and ectoderm very important process - as the germ layers are precursors for organs of fetus

Question 32

describe the process of gastrulation

Answer 32

(occurs in 3rd week post-fertilisation) thickened structure forms in midline of embryo near caudal end → this is the primitive streak at cranial end primitive streak expands to form primitive node primitive pit (circular depression) forms in primitive node primitive pit extends along midline towards caudal end of streak → forms primitive groove once primitive groove has formed there is invagination of epiblasts through primitive groove the epiblasts that migrate through the groove then invade hypoblasts and replace them → forms definitive endoderm epiblasts which continue to migrate through primitive groove once endoderm has formed, deposit to form a new layer (between the epiblasts and endoderm) → mesoderm once endoderm and mesoderm have formed the remaining epiblasts which did not migrate is called the ectoderm whole process is the formation of 3 germ cell layers from bilaminar disc (cells in different layers are exposed to differentiate environments → signals them to become different derm layers)

Question 33

what is the significance of the primitive streak

Answer 33

thickening of epiblasts defines the major planes of the body: divides it into left and right (as it forms in the midline) and cranial and caudal (forms closer to caudal end)

Question 34

label the germ cell layer

Answer 34

Question 35

fill in this table on the organs derived from each germ layer

Answer 35

Question 36

what is the first major event which occurs after gastrulation describe what happens why is it significant

Answer 36

formation of the notochord - occurs around day 13+ notochord forms from primitive streak and grows along the midline towards the cranial end of the embryo **forms underneath the ectoderm** rod-like tube formed of cartilaginous-like cells important as the notochord acts as a key organizing centre for **neurulation** (process of CNS development) and mesoderm development (especially important for muscles)

Question 37

describe the process of neuralation

Answer 37

process in which neural plate forms the neural tube (which then goes on to form CNS) - directed by notochord notochord acts as the major signalling organiser for neurallation notochord (underneath ectoderm) sends signals to the neural plate above it (neural plate is an area of thickened ectoderm) the signals from the notochord stimulate the neural plate ectoderm to invaginate → formation of neural groove and for 2 area of neural plate to rise up and form ridges → formation of neural folds (which run along cranio-caudal axis) neural crest cells in neural folds are specified over next few days neural folds move closer to each and fuse together over neural groove → forms hollow neural tube as the neural tube forms the neural crest cells migrate away from folds

Question 38

label this diagram what process is occurring here

Answer 38

Question 39

label the diagram what process has just occurred to form this structure what will happen next

Answer 39

neurulation - formation of neural tube from neural plate can see that the neural tube has a complete lumen → therefore neural ridges have fused across length of the embryo and epidermis has formed over the top (derived from ectoderm) and that neural crest cells have migrated away from folds now the ends of the neural tube need to close, head end will close at day 23, tail end will close at day 27 (neurulation begins in around day 13+ and continues into 4th week)

Question 40

why is closure of the neural tube important

Answer 40

closure at head end = day 23 closure at tail end = day 27 head end needs to close in order for brain structures to form failure of neural tube closure is common birth defect: head end failure (much more drastic) - ancephaly tail end failure - spina bifida

Question 41

what are neural crest cells what is their function

Answer 41

neural crest cells are multipotent ectoderm derived cells which are highly plastic and migrate extensively from neural folds during development: they are classified according to where they end up in the embryo → lead to formation of various tissues in each location

Question 42

what is the clinical significance of neural crest cells

Answer 42

defects of neural cell migration and specification are relatively common - problems with them going to the right location and developing into the right cell when they are there can cause a diverse range of birth defects depending on which neural crest cells are affected trunk NC → pigmentation disorders cranial NC → deafness, facial defects cardiac NC → cardiac defects vagral and sacral NC → faecal defects + no gut innervation

Question 43

what are somites how do they form

Answer 43

pairs of condensed blocks of paraxial mesoderm formed through somitogenesis: paraxial mesoderm is found on either side of the neural tube (above notochord) blocks of paraxial mesoderm condense in pairs (one on either side of neural tube) and bud off (appear) at the same time → synchronized budding to form somites somitogenesis starts at cranial end and progress towards caudal end down long axis occurs in segmented animals rate at which the somites bud (appear) and the number of somite pairs is species specific in humans 1 par buds every 90mins and there are 44 pairs

Question 44

what is shown in this picture what can be noted about their appearance

Answer 44

somites - paired blocks of condensed paraxial mesoderm on either side of the neural tube in humans they will stop forming at 44 pairs somites closer to the cranial end are more defined than the caudal → this makes sense as somite formation begins at the cranial end

Question 45

why are somites important how do they do this

Answer 45

they give rise to important mesodermal tissues

Question 46

label this diagram

Answer 46

Question 47

how does the gut form in the embryo

Answer 47

primitive gut forms around day 16+: ventral folding - cranial and caudal ends of embryo fold inwards together lateral folding - both side of embryo fold inwards together ventral and lateral folding cause section of yolk sac (derived from hypoblasts) to be pinched off this pinched off part forms primitive gut → then is subdivided into foregut, midgut and hindgut

Question 48

what does the foregut give rise to

Answer 48

endoderm derived

Question 49

what does the midgut give rise to

Answer 49

endoderm derived

Question 50

what does the hindgut give rise to

Answer 50

endoderm derived

Question 51

what germ layer is the heart derived from when does it start to form when does it start pumping blood

Answer 51

mesoderm

Question 52

what germ layer are the lungs derived from when do they start to form

Answer 52

endoderm

Question 53

what germ cell layer are the gonads derived from how do they become sex specific

Answer 53

mesoderm

Question 54

draw flow chart of cell lineages that form from morula onwards

Answer 54

Question 55

following gastrulation what are the major events that occur in order

Answer 55