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BRS 1: Development & Aging Domain > Overview > Flashcards

Overview Flashcards

1
Q

Three stages of embryo development

A

Embryogenic
Embryonic
Foetal

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2
Q

What occurs in the Embryogenic stage

A

Genesis of embryo
Pluripotent Stem Cells and extraembryonic stem cells
First trimester, 14-16 days post fertilisation

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3
Q

What occurs in the embryonic stage

A

Development of germ layers and body plan
Occurs during first trimester 16-50 days post fertilisation

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4
Q

What occurs in the foetal stage

A

Organ system migration
Growth and viability determined
Spans second and third trimester 50-270 days

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5
Q

What are some different measurements of the age of an embryo?

A
  • Fertilisation age- days since last ovulation plus 1
  • Gestational age- days since the start of the last period plus 14
  • Carnegie stage- 23 stages, based on the features of the embryo and not time.
    This can measure upto 60 days, and allows for comparison between different species.
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6
Q

6 stages of embryo development

A
  1. Fertilisation
  2. Cleavage
  3. Compaction
  4. Implantation
  5. Gastrulation
  6. Neurulation
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7
Q

What is the cleavage stage and how long does it last

A

Newly formed zygote begins to divide from 1cell to 8cells
1-4 days

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8
Q

What is an embryo known as following cleavage stage?

A

A morula
16-200 cells in size

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9
Q

At what point does the development of the embryo come under exclusive control of the zygotic genome, and what is this point known as?

A

The point of cleavage stage when 4 cells divide to from 8 cells .
Known as either :
Maternal to zygomatic transition (MZT)
Embryonic genome activation (EGA)

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10
Q

How is development of the embryo controlled before MZT / EGA

A

Via maternal mRNA

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11
Q

Describe the compaction stage

A

Outer cells of zygote flatten out as they are pushed against zona pellucida
Inner cells form attachments - tight junctions and desmosomes

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12
Q

Describe the blastocyst

A

Day 5-6
Stage of zygote following compaction
Zygote hatches from zona pellucida, forming trophoectoderm and inner cell mass (2regions of cell form)
Blastocoel cavity forms

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13
Q

Why does the blastocoel cavity form?

A

Trophectoderm cells pump Na+ into cavity, followed by water

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14
Q

What day does peri-implantation occur

A

Around day 7-9

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15
Q

What cell populations arise from peri-implantation stage which leads to two distinct regions

A

Trophectoderm - Cytotrophoblast cells, syncitiotrophoblast cells
Inner cell mass - Epiblast, Hypoblast

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16
Q

Function of cells in Trophectoderm

A

Cytotrophoblast cells - stem cells giving rise to syncitiotrophoblasts

Syncitiotrophoblast- destroy uterine endometrium to allow for implantation

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17
Q

3 events of day 12

A

Bi-laminar disc begins to form
Epiblast and Hypoblast form amniotic cavity
Syncitiotrophoblasts begin to secrete beta hCG

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18
Q

Describe gastrulation

A

Day 14
Determination of body axis, formation of germ layers
Primitive streak - determines body axis, gives rise to germ layers as cells migrate down invagination
Epiblast cells are first to migrate and form endoderm
Remaining Epiblast cells above primitive stream form ectoderm
Remaining Epiblast cells between ectoderm and endoderm form mesoderm

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19
Q

Which systems and organs do each germ layer form?

A
  1. Endoderm- GI tract, the liver, pancreas, lung, thyroid
  2. Ectoderm- Central nervous system, neural crest, skin epithelia, tooth enamel
  3. Mesoderm- blood, muscle, gonads, kidneys, adrenal cortex, bone, cartilage
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20
Q

Outline the 4 key events of days 13-17.

A
  • Notogenesis
  • Neurulation
  • Somitogenesis
  • Formation of the gut tube
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21
Q

What is neurulation?

A

Neurulation describes the formation of the neural tube driven by the notochord.

The notochord is a mesoderm-derived structure in the embryo which drives cell migration. This is important for neurulation as it stimulates the ectoderm to form the neural plate.

The neural plate is then further stimulated to invaginate, forming the neural groove and the two neural folds, where the multipotent neural crest stem cells can be found.

The neural folds fuse to form the neural tube from the neural groove, and the neural tube is overlaid with epidermis.

The neural tube initially remains open, however the head end usually closes by day 23, and the tail end usually closes by day 27

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22
Q

What are some problems which may arise if the neural tube doesn’t close? (8)

A
  • Anencephaly- brain does not develop due to head-end opening
  • Spina bifida
  • Deafness
  • Cardiac defects
  • Facial defects
  • Gut innervation defects
  • Pigmentation defects
  • Encephalocele
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23
Q

Where may the neural crest cells migrate and what do they give rise to?

A
  • Cranial NCs- cranial neurones, glia, lower jaw, middle ear bones, facial cartilage
  • Cardiac NCs- aortic arch / pulmonary artery septum, large artery wall muscle
  • Trunk NCs- dorsal root ganglia, sympathetic ganglia, adrenal medulla, aortic nerve clusters, melanocytes
  • Vagral & Sacral NCs- parasympathetic ganglia, enteric nervous system ganglia
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24
Q

Describe somitogenesis.

A

The formation of somites, from paired blocks of paraxial mesoderm which flank the neural tube and notochord.

The somites begin to form at the head and are formed down the axis.

The somites develop into:

  • Sclerotome- giving rise to the bones, ribs and cartilage
  • Dermomytome- which splits into the dermatome and the myotome.
  • Dermatome- gives rise to the dermis
  • Myotome- gives rise to the muscles
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25
Q

What is the primitive tube and how is it formed?

A

The primitive gut formed from the yolk sac by ventral and lateral folding.

-

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26
Q

What three regions does the primitive tube form, and what do they consist of?

A
  1. Foregut- oesophagus, stomach, upper duodenum, liver, gallbladder, pancreas
  2. Midgut- lower duodenum, remainder of small intestine, ascending colon, first two thirds of transverse colon
  3. Hindgut- last third of transverse colon, descending colon, rectum, upper anal canal
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27
Q

How does the heart develop in utero?

A

From the tube of mesoderm around day 19, beating by day 22.

The foetal heartbeat is detectable by around 6 weeks

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28
Q

How do the lungs develop in utero?

A

The lungs arise from the lung bud and also the endodermal structure adjacent to the foregut.

They split into two at the end of week 4, and progressively branch.

29
Q

How do the gonads develop in utero?

A

The gonads develop from the mesoderm as bipotential structures known as gonadal/genital ridges.

30
Q

What gene is linked to the development of testis/ovaries?

A

The SRY gene- present in the Y chromosome.

This directs gonadal cells to become Sertoli cells, triggers development of the testis and leads to formation of Leydig cells, and testosterone production.

The absence of the SRY gene causes gonadal cells to adopt a granulosa cell fate and causes ovary development, which is enforced by the FOXL2 gene

31
Q

What are the 3 main causes of early pregnancy loss?

A
  • Aneuploidy
  • Failure of embryo to implant
  • Unsustained development of implanted embryo
32
Q

Define miscarriage.

A

The loss of a pregnancy prior to 23 weeks of gestation

33
Q

What constitutes as an early clinical pregnancy loss?

A

Any pregnancy loss before 12 weeks of gestation

34
Q

What constitutes as a late clinical pregnancy loss?

A

Loss of a pregnancy after 24 weeks of gestation

35
Q

Define Recurrent Miscarriage (RM) / Recurrent Pregnancy Loss (RPL)

A

The definition of this is different depending on state, but in the UK the definition is three or more pregnancy losses, either consecutive or not.

-

36
Q

How can maternal age cause aneuploidy?

A
  • Oocytes undergo meiosis whilst the foetus is in the womb
  • Homologous pairs cross over before the second meiotic division, and stay crossed over for a prolonged period of time
  • These oocytes remain in this state until they are mature, this is referred to as oocyte meiotic arrest
  • Oocyte meiotic arrest can last up to 50 years
  • The pairs of homologous proteins are held together by cohesin protein such as REC8 and SMC2.
  • These cohesins are fewer in number as a person ages, and so deterioration of cohesins can lead to aneuploidy
37
Q

What is genetic imprinting?

A

The ability of a gene to be expressed is dependant on the sex of the parent passing in the gene

38
Q

What are parthenogenetic and androgenetic embryos?

A

These terms both describe embryos with two sets of haploid chromosomes from the same parent.

Parthenogenetic = two sets of haploid chromosomes from mother

Androgenetic = two sets of haploid chromosomes from father

39
Q

What are benign growths of the uterus due to nonviable egg implantation called?

A

Hydatidiform moles. They can be complete (there is no foetal tissue) and partial (there is some foetal tissue)

40
Q

What are 3 forms of gestational trophoblastic neoplasia?

A
  • Invasive moles
  • Choriocarcinoma
  • Placental site trophoblastic tumour
41
Q

What percentage of pregnancies are ectopic, and what percentage of ectopic pregnancies occur in the fallopian tubes?

A

Between 1 and 1.15% of pregnancies are ectopic, with 98% of these occurring in the fallopian tubes.

42
Q

Why are ectopic pregnancies medical emergencies?

A

They are nonviable pregnancies and can rupture, leading to haemorrhage and potentially death of the mother.

43
Q

What are some risk factors for ectopic pregnancies?

A

Smoking and past ectopic pregnancies are risk factors.

Some theorised risk factors include IVF, cannabis smoking, and becoming pregnant older than 35

44
Q

How do early embryos gain nutrition?

A

Histiotrophic support- uterine gland secretions and the breakdown of endometrial tissue provide nutrients

45
Q

How do embryos gain nutrition from the start of the 2nd trimester?

A

Haemotrophic support- through haemochorial-type placenta, where maternal blood contacts the foetal membrane.

46
Q

What are the two foetal membranes?

A
  1. Amnion (inner foetal membrane)
  2. Chorion / Trophectoderm (outer foetal membrane)
47
Q

What is the allantois?

A

The outgrowth of the yolk sac along the connecting stalk from the embryo to the chorion, which is coated in mesoderm and eventually vascularises to form the umbilical cord.

48
Q

Describe the formation of chorionic villi.

A

Cytotrophoderm in the chorion extend into the placenta- forming the initial cavity. This is the primary chorionic villus.

Mesoderm cells coat the cavity. This is the secondary chorionic villus

Blood vessels enter the villi. This is the tertiary chorionic villus.

Extravillous trophoblastic cells invade maternal spiral arteries, where they become endovascular extravillous trophoblast cells. These cells widen the arteries to lower the pressure of the blood within. Failure to do this can result in pre-eclampsia.

-

49
Q

By what mechanism does the foetus receive Oxygen?

A

Higher foetal haemoglobin oxygen affinity, alongside low foetal O2 tension and high maternal O2 tension

50
Q

By what mechanism does the foetus receive glucose?

A

Facilitated diffusion

51
Q

By what mechanism does the foetus receive water?

A

Diffusion

52
Q

By what mechanism does the foetus receive electrolytes?

A

Some by diffusion, some by active co-transport

53
Q

By what mechanism does the foetus receive calcium?

A

It is actively pumped

54
Q

By what mechanism does the foetus receive amino acids?

A

Active transport to foetus, reduced maternal urea excretion

55
Q

Describe late foetal development of the circulatory system

A
  • The gas exchange surface for the foetus is at the placenta
  • Ventricles act in parallel
  • Vascular shunts bypass the pulmonary and hepatic circulation, though these close at birth
56
Q

Describe late foetal development of the respiratory system.

A
  • Primitive air sacs develop and surfactant is produced at around 20 weeks.
  • The primitive air sacs have vascularised by 28 weeks
  • The production of surfactant is upregulated by term
  • The foetus shows rapid respiratory movements during REM, for 1-4 hours each day
57
Q

Describe late foetal development of the Gastrointestinal system.

A
  • Endocrine pancreas function from start of term 2, insulin production from mid term 2
  • Liver glycogen is progressively deposited, this accelerated towards term
  • Large amounts of amniotic fluid are swallowed, debris and bile acids form meconium
58
Q

Describe late foetal development of the nervous system.

A
  • Foetal movements begin in late T1, detectable from ~14 weeks
  • Stress response from 18 weeks
  • Thalamus-cortex connections by 24 weeks
  • ## No conscious wakefulness, only slow-wave or REM sleep
59
Q

What are the three stages of labour?

A
  1. First stage- contractions begin, cervix dilates. This occurs in two phases:
    The latent phase- slow dilation to 2-3cm
    The active phase- rapid dilation to 10cm
    This can be long lasting (around 14 hours but potentially more)
  2. Second stage- Delivery of foetus
    This commences at 10cm dilation
    There are maximal myometrial contractions- intense and frequent
    This usually lasts 1-2 hours
  3. Third stage- expulsion of placenta and foetal membranes (afterbirth)
    Post-partum repair
60
Q

What are the four stages of cervix remodelling?

A
  1. Softening- measurable changes in compliance, but competency remains. This begins in the 1st trimester
  2. Ripening- monocytes infiltrate the cervix, IL-6 and IL-8 are secreted and hyaluronic acid is deposited. This occurs weeks or days before birth.
  3. Dilation- increased elasticity, increased hyaluronidase expression, increased hyaluronic acid breakdown, and decreased collagen content due to MMP activity. Occurs during labour
  4. Post-partum repair- recovery of tissue integrity and competency

Removal of collagen and hyaluronic acid leads to more elasticity

61
Q

How is the timing of parturition thought to be determined?

A

By changes in the foetal HPA axis.

This is because CRH promotes foetal ACTH and cortisol release, and increased cortisol release drives placental production of CRH- positive feedback.

CRH levels rise exponentially in the mother towards the end of pregnancy, and there is a decline in CRH-binding protein levels, so the level of bioavailable CRH increase.

There is also an increase in DHEAS production in the foetal adrenal cortex

62
Q

How does labour proceed despite high progesterone levels?

A

Progesterone receptors switch from the active signalling isoform PR-A, to the repressive isoforms PR-B & PR-C.

This causes a functional progesterone withdrawal.

In addition, there is increased oestrogen receptor alpha expression.

This means that the uterus becomes non-responsive to progesterone and sensitised to oestrogen.

63
Q

How do rising oestrogen levels impact prostaglandin synthesis?

A

Rising oestrogen levels increase prostaglandin synthesis in two ways:

  1. Increased activation of phospholipase A2 enzymes, generating arachidonic acid which is used in prostaglandin synthesis
  2. Increased stimulation of oxytocin receptor expression promotes prostaglandin release
64
Q

What three prostaglandins are important for pregnancy and what are their roles?

A
  1. PGE2 - cervix remodelling - promotes leukocyte infiltration, IL-8 release and collagen bundle remodelling
  2. PGF2-alpha - myometrial contractions - destabilises membrane potentials and promotes connectivity of myocytes with oxytocin
  3. PGI2 - myometrium - promotes myometrium muscle relaxation, relaxation of lower uterine segments and is important for relaxation of myometrium between contractions to allow blood flow to placenta.

Relaxins and nitric oxide are also implicated in cervical remodelling

65
Q

At what week does the foetal head engage with the pelvic space?

A

Between weeks 34-38. If this doesn’t occur, the baby is known as a breech baby, and a C section must be performed.

66
Q

What does pressure on the foetus cause?

A

The chin to press against the chest (flexion)

67
Q

What way should the foetus be facing?

A

Belly towards the spine of the mother following rotation, head towards the cervix following engagement of head with pelvic space.

68
Q

What events occur after delivery of the baby?

A
  • Rapid shrinkage of the uterus- area of contact between placenta with endometrium shrinks
  • Folding of foetal membranes
  • Collapse of villi following the clamping of the umbilical cord
  • Formation of hematoma between decidua & placenta
  • Contractions expel the placenta and any remaining foetal tissue

BRS 1: Development & Aging Domain (4 decks)

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