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BRS YR2 > Early Fetal Development > Flashcards

Early Fetal Development Flashcards

1
Q

What are the possible causes of pregnancy loss?

A
  • errors in embryo-fetal development
  • failure of the embryo to implant in the uterine lining
  • unable to sustain the development of an implanted embryo/fetus
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2
Q

What is a miscarriage?

A

loss of a pregnancy prior to 23 weeks gestation

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3
Q

What is early clinical pregnancy loss?

A

<12 weeks gestation

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4
Q

What is late clinical pregnancy loss?

A

> 24 weeks gestation

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5
Q

What is a recurrect miscarriage/recurrent pregnancy loss?

A

UK: 3 or more pregnancy losses

US/EU: 2 or more

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6
Q

How to detect a pregnancy?

A
  • hcG test

- fetal heartbeat

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7
Q

What is a pre-clinical pregnancy loss?

A
  • pre-implantation (30%)

- post-implantation (30%) (3-4weeks gestation)

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8
Q

What is the most common cause of pregnancy loss before 12 weeks gestation?

A

Aneuploidy (50%)

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9
Q

Why does aneuploidy increase with maternal age?

A
  • during f meiotic arrest, the chromatids of homologous chromosomes are held together by cohesin proteins
  • cohesin proteins are not replaced, leading to loss of cohesion between chromatids with increasing age of the oocyte
  • If cohesion is lost, chromatids can separate and drift during meiotic division, rather than being segregated accurately by the spindle.
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10
Q

What signalling pathway underpins recurrent pregnancy loss?

A
  • Reduced levels of LIF in the uterine secretions of subfertile women (impacting implantation)
  • Non-selective uterus hypothesis
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11
Q

What is the non-selective uterus hypothesis

A
  • Uterus permits implantation of poor quality embryos

- Changes in uterine mucin expression in women with RM/RPL

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12
Q

What is required for viable development of the fetus and the placenta?

A

maternal and parentally-derived genomes

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13
Q

Why is maternal and paternal genomes required for normal fetal development?

A

imprinted genes

  • paternal: embryo>mother
  • maternal: restrict embryo for future pregnancies
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14
Q

What are Gestational Trophoblastic Diseases (GTD)?

A

a collection of disorders characterised by overgrowth of trophoblastic tissue

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15
Q

What are the 2 different types of GTDs?

A
  • benign (hydatidiform moles)

- malignant (gestational trophoblastic neoplasias)

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16
Q

How do complete hydatidiform moles arise?

A

empty egg fertilized by:

  • 1x sperm with genome duplication
  • 2 x sperm.
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17
Q

How do partial hydatidiform moles arise?

A

normal egg fertilized by:

  • 1x sperm with genome duplication
  • 2 x sperm
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18
Q

What may underly recurrent hydatidiform moles?

A

NLRP7 mutations

failure to recognise and clear a failed pregnancy

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19
Q

What is an ectopic pregnancy?

A

Implantation of the embryo at a site other than the uterine endometrium

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20
Q

Where do most ectopic pregnancies occur?

A

98% in the fallopian tube

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21
Q

How common are ectopic pregnancy?

A

1-1.5% of pregnancies

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22
Q

What are the treatment options for ectopic pregnancies?

A
  • expectant managemnet
  • chemotherapy (methotrexate)
  • surgery to remove the trophoblast +/- tube
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23
Q

What are the main risk factors for ectopic pregnancy?

A
  • history of ectopic pregnancies + infertility
  • certain STIs
  • Pelvic Inflammatory Disease
  • Endometriosis
  • maternal age >35yo
  • cannabis use (mothers)
  • smoking (mothers)
  • IVF
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24
Q

How does cigarette smoking increase the risk of the ectopic pregnancy?

A

Continine:

  • regulates the expression of PROKR1, a regulator of fallopian tube smooth muscle contractility.
  • induces pro-apoptosis protein expression in fallopian tube explants

Tobacco smoke inhibits ciliary function&raquo_space; ?reduce tubal transit of the embryo

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25
Q

How does cannabis use affect the fallopian tube?

A
  • reduced CB1 receptor (cannaboid receptor in fallopian tubes) levels
  • THC acts directs, perturbing embryo transit
    (embryo retention in mice)
  • endocannabinoid levels are elevated in ectopic pregnanies
  • THC may act directly on fallopian tube to delay embryo transport
  • alter the balance of endocannabinoids (the tone), balance of production and breakdown of endocannabinoids, leading to a disruption to the embryo environment
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26
Q

What 2 types of folding does the primitive gut arise from?

A
  • ventral folding (head and tail end curl together)

- lateral folding (where the 2 sides of the embryo roll)

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27
Q

What is the fertilisation age?

A
  • measured from time of fertilisation (+1 day from last ovulation)
  • difficult to know the exact time of fertilisation (IVF)
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28
Q

What is the gestational age?

A
  • calculated from the time of the beginning of the last menstrual period
  • determined by the fertilization date (+14 days) if known, or early obstetric ultrasound and comparison to embryo size charts
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29
Q

What is the carnegie stage?

A
  • 23 stages of embryo development based on features not time
  • allows comparison of development rates between species
  • covers the window of 0-60 days fertilization age in humans
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30
Q

When is the embryogenic stage?

A

14/16 days post fertilisation

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31
Q

What is the embryogenic stage?

A
  • establishing the early embryo from the fertilised oocyte
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32
Q

What is the embryogenic stage characterised by?

A

the formation of:

  • pluripotent embryonic cells (fetus)
  • extaembryonic cells (contribute to the support structures like the placenta)
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33
Q

When is the embryonic stage?

A

16-50 days post fertilization

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34
Q

What is the embryonic stage characterised by?

A
  • establishment of the germ layers and differentiation of tissue types
  • establishment of the body plan
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35
Q

When is the fetal stage?

A

50-270 days post fertilisation

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36
Q

What is the fetal stage characterised by?

A
  • major organ systems are now present
  • migration of some organ systems to the final location
  • extensive growth and acquisition of fetal viability (survival outside of the womb)
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37
Q

What makes up the first trimester?

A

first 12 weeks of pregnancy

  • embryogenic stage
  • embryonic stage
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38
Q

What makes up the second and third trimester?

A
  • fetal stage

12 week

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39
Q

When does the transition between embryo to fetus occur?

A

at the end of the first trimester

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40
Q

What is the structure formed immediately after fertilisation?

A

zygote (1 cell)

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41
Q

What does the zygote develop into?

A

cleavage stage embryos

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42
Q

How many cells are in cleavage stage embryos?

A

2-8 cells

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43
Q

What does the cleavage stage embryos (8 cells) develop into?

A

morula (16+ cells)

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44
Q

What does a morula (16 cells) develop into?

A

blastocyst (200-300 cells)

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45
Q

Where are all of these divisions occuring in?

A

the zona pellucida

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46
Q

When does the maternal-zygotic transition occur?

A

at the 4-8 cell stage

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47
Q

What happens before the maternal-zygotic transition?

A
  • none of the genes of the embryo are transcribes

- the embryo relies on maternal mRNAs and proteins to get through the first divisions

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48
Q

Where does the embryo get the maternal mRNA and proteins needed to get through the first divisions?

A

they are synthesized and stored during oocyte development pre-ovulation

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49
Q

What happens if the embryo does not have these maternal mRNAs and proteins to get through the first divisions?

A

failure to synthesise, store or interpret may impair embryonic development

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50
Q

What happens in the maternal-to-zygotic transition?

A
  • transcription of embryonic genes (zygotic genome activation)
  • increased protein synthesis
  • organelle (mitochondria, Golgi) maturation
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51
Q

When does compaction occur?

A

at 8 cell stage or later (morula)

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52
Q

What is the result of the compaction?

A

the formation of the first 2 distinct cell types

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53
Q

What happens in compaction?

A
  • outer cells are pressed against the zona pellucida
  • change from spherical to wedge shaped
  • outer cells connect through tight gap junctions and desmosomes
  • forms barriers to diffusion between inner and outer embryo
  • outer cells become polarized
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54
Q

What happens when a compacted morula develops into a blastocyst?

A

inner and outer cells reorganise to form the blastocoel cavity

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55
Q

What is the Zona Pellucida?

A

hard protein shell inhibiting polyspermy and protects the early embryo

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56
Q

What do the inner cells formed in compaction give rise to?

A

pluripotent embryonic cells (contribute to fetus)

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57
Q

What do the outer cells formed in compaction give rise to?

A

extra-embryonic cells that contribute to the extra-embryonic cells

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58
Q

What is the name given to the outer cell border formed during compaction?

A

trophoectoderm

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59
Q

What is a Blastocoel?

A

fluid-filled cavity formed osmotically by trophoblast pumping Na+ ions into the cavity

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60
Q

When does hatching occur?

A

day 5-6

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61
Q

Why does hatching occur?

A
  • to escape the zona pellucida

- to implant the blastocyst

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62
Q

How does hatching occur?

A
  • enzymatic digestion

- cellular contraction

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63
Q

When do the peri-implantation events occur?

A

day 7-9

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64
Q

What happens on the initial implantation of the blastocyst to the uterine endometrium?

A
  • trophoectoderm separates into the syncytiotrophoblast
    and cytotrophoblast
  • inner cell mass seperates into an epiblasts and hypoblasts
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65
Q

What is a syncytiotrophoblast?

A
  • invasive
  • destroys local materal cells in the endometrium
  • creates interface between embryo and maternal blood supply
66
Q

What is a cytotrophoblast?

A

cells that remain individual to provide a source of syncytiotrophoblast cells

67
Q

What are epiblasts?

A

cells that the fetal tissues will derive from

68
Q

What are hypoblasts?

A

cells that form the yolk sac (extraembryonic structure)

69
Q

When is the bi-laminar embryonic disc formed?

A

day 12+

70
Q

What happens in the bi-laminar embryonic disc formation?

A
  • some cells seperate from epiblasts due to the formation the amniotic cavity
  • the amnion cells with contribure to the extra-embryonic membranes
  • the leaves a 2-layer disc of epiblast and hypoblast
71
Q

What is the embryo ready for when the formation of the bi-laminar embryonic disc has occured?

A

gastrulation

72
Q

What is secreted by syncytiotrophoblasts?

A

hCG

73
Q

When is hCG secreted by syncytiotrophoblasts?

A

when the bi-laminar embryonic disc has formed

74
Q

What process follows the formation of the bilaminar embryonic disc?

A

gastrulation

75
Q

What is gastrulation?

A

the process where the bi-laminar embryonic disc undergoes reorganisation to form a tri-laminar disc

76
Q

When does gastrulation start?

A

15 days after fertilization

77
Q

What is the primitive streak?

A
  • a thickened structure formed on the midline in the epiblasts (near the caudal end)
78
Q

What does the formation of the primitive streak define?

A
  • the major body axes of the embryo

- cranial and caudal end, and left and right side

79
Q

What happens at the cranial end of the embryonic disc?

A

the primitive streak expands to create a primitive node containing the primitive pit (that continues to the caudal end) to form a primitive groove

80
Q

What happens once the primitive groove has been formed?

A

the cells of the epiblast migrate inwards, towards the streak, detach from the epiblast and slip in into the interior of the embryo

81
Q

What process happens once the primitive groove has been formed?

A

invagination

82
Q

Describe the process of invagination.

A

the cells of the epiblast migrate inwards, towards the streak, detach from the epiblast and slip in into the interior of the embryo (between the 2 layers of the embryonic disc)

83
Q

What happens when epiblasts invaginate through the primitive groove?

A
  • invade the hypoblast
  • displace the hypoblast cells
  • eventually replaced by a new proximal cell layer, the definitive endoderm
84
Q

How is the definitive endoderm formed?

A
  • the epiblasts invade the hypoblast, displace the hypoblast cells
  • eventually replaced by a new proximal cell layer, the definitive endoderm
85
Q

When has the majority of the hypoblast been replaced?

A

by day 16

86
Q

What happens to the remaining cells of the epiblast that don’t move through the primitive groove?

A

form the ectoderm

87
Q

What is the ectoderm?

A

the most exterior, distal layer

88
Q

What happens to the invaginated epiblast cells that remain in the space between the ectoderm and the the definitive endoderm?

A

form the mesoderm

89
Q

What forms the mesoderm?

A

invaginated epiblast cells that remain in the space between the ectoderm and the the definitive endoderm

90
Q

What happens when the formation of the definitive endoderm and the mesoderm is complete?

A

epiblast cells no longer migrate towards the primitive streak

91
Q

What happens to the ectoderm throughout gastrulation?

A

the ectoderm continues to form from the cranial to the caudal end of the embryo

92
Q

What layer is closest to the cranial end?

A

the ectoderm

93
Q

What layer is closest to the caudal end?

A

the definitive endoderm

94
Q

What indicates that gastrulation is complete?

A

the formation of 3 distinct primary germ layers

95
Q

What organs does the endoderm give rise to?

A
  • GI tract
  • liver, pancreas
  • lung
  • thyroid
96
Q

What organs does the ectoderm give rise to?

A
  • CNS and neural crest
  • skin epithelia
  • tooth enamel
97
Q

What organs does the mesoderm give rise to?

A
  • blood (endothelial cells, RBCs, WBCs)
  • muscle (smooth, skeletal and cardiac)
  • gonads
  • kidneys and adrenal cortes
  • bone and cartilage
98
Q

What happens after gastrulation?

A

the formation of the notochord

99
Q

What is the notochord?

A

a rod-like tube structure formed of cartilage-like cells

100
Q

Where does the notochord form?

A
  • from the primitive streak
  • towards the head of the embryo
  • under the ectoderm
101
Q

What is the funciton of the notochord?

A
  • key organizing centre for neurulation (releases growth factor signals) and mesoderm development
102
Q

How does the notochord control the development of the neural system?

A

controlling the neural plate

103
Q

What is the neural plate?

A

an thickened area of ectoderm that sits on top of the embryo

104
Q

What is the neural tube?

A

signals from the notochord move through the embryo and direct the neural plate to form it

105
Q

How does the notochord form the CNS?

A
  • the notochord sends signals to the neural plate
  • for a part to invaginate to move towards the notochord to form the neural groove
  • for 2 areas of the neural plate to move up, creating 2 crests called the neural fold
106
Q

Where do the neural folds run?

A

along the cranio-caudal axis

107
Q

What is within these neural folds?

A

specified neural crest cells

108
Q

What happens to the neural folds as development progresses?

A
  • neural folds move together over the neural grove
  • they fuse, forming a hollow tube
  • this tube it overlaid with epidermis (ectoderm)
  • migration of the neural crest cells from neural folds
109
Q

What is neurulation?

A

the formation of the neural tube and CNS

110
Q

What happens to the neural tube as development occurs?

A
  • closure at tail and head end

- closure at head end precedes the formation of brain structures

111
Q

When does the closure of the head end of the neural tube occur?

A

around day 23

112
Q

When does the closure of the tail end of the neural tube occur?

A

day 27

113
Q

What defects are associated with failure of the neural tube closure?

A
  • anencephaly

- spina bifida

114
Q

What is anencephaly?

A

absence of most of the skull and brain, due to head end closure failure
(1/10,000)

115
Q

What is spina bifida?

A

open neural tube at birth, usually lower spine due to failure to close tail end - varying severity
(0.4-5/1000)

116
Q

What are neural crest cells?

A
  • ectoderm derived
  • plastic
  • migrate extensively during development
117
Q

What are the different derivative of neural crest cells?

A
  • cranial NC
  • cardiac NC
  • trunk NC
  • Vagral and Sacral NC
118
Q

What do cranial neural crest cells contribute to?

A
  • cranial neurones
  • glia
  • lower jaw
  • middle ear bones (ossicles)
  • facial cartilage
119
Q

What do cardiac neural crest cells contribute to?

A
  • aortic arch/pulmonary artery septum

- large artery wall musculoconnective tissue

120
Q

What do trunk neural crest cells contribute to?

A
  • dorsal root ganglia
  • sympathetic ganglia
  • adrenal medulla
  • aortic nerve clusters
  • melanocytes
121
Q

What do vagral and sacral neural crest cells contribute to?

A
  • parasympathetic ganglia

- enteric nervous system ganglia

122
Q

What do defects of neural crest migration/specification lead to?

A

diverse birth defects including:

  • pigmentation disorders
  • deafness
  • cardiac and fetal defects
  • failure to innervate the gut
123
Q

What comes after neurulation and neural tube formation?

A

somitogenesis

124
Q

What is somitogenesis?

A

the formation of blocks of mesoderm along the axis of the embryo, somites

125
Q

What are somites?

A

arise from paired blocks of paraxial mesoderm flanking the neural tube and notochord

126
Q

What happens in somitogenesis?

A
  • blocks of paraxial mesoderm condense and bud off in somite pairs
  • one of each pair either side of the neural tube
  • starts at the head end and progresses towards the tail down the long axis
  • rate of budding is species specific, (1 pair/90 minutes, 44 pairs)
127
Q

What are the mesodermal tissues that are derived from somites?

A
  • sclerotome

- dermomyotome.

128
Q

What does the sclerotome give rise to?

A
  • vertebrae

- rib cartilage

129
Q

What does the dermomyotome give rise to?

A
  • dermatome

- myotome

130
Q

What does the dermatome give rise to?

A
  • dermis of the skin
  • some fat
  • connective tissues of the neck and trunk
131
Q

What does the myotome give rise to?

A

the muscles of the embryo

132
Q

When does the formation of the gut tube tend to occur?

A

day 16+

133
Q

What is the yolk sac involved in?

A

early hematopoiesis along with other developmental processes

134
Q

What is the yolk sac derived from?

A

the hypoblasts

135
Q

What does the primitive gut arise from?

A

2 types of folding in the embryo

  • ventral
  • lateral
136
Q

What is ventral folding?

A

where the head and tail ends curl together

137
Q

What is lateral folding?

A

where the 2 ends of the embryo roll

138
Q

What does the folding achieve?

A

it pinches off part of the yolk sac to form the primitive gut

139
Q

What is the primitive gut organised into?

A
  • foregut
  • midgut
  • hindgut
140
Q

What is derived from the foregut?

A
  • esophagus
  • stomach
  • upper duodenum
  • liver
  • gallbladder
  • pancreas
141
Q

What germ layer is the gut derived from?

A

the endoderm

142
Q

What is derived from the midgut?

A
  • lower duodenum and rest of small intestine
  • ascending colon
  • first 2/3 of the transverse colon
143
Q

What is derived from the hindgut?

A
  • last 1/3 of the transverse colon
  • descending colon
  • rectum
  • upper anal canal
144
Q

What germ layer does the heart derive from?

A

the mesoderm

145
Q

When does the heart start forming?

A

day 19

146
Q

When does heart beating and pumping blood commence?

A

day 22

147
Q

When is a fetal heart beat detectable?

A

from around 6 weeks gestational age

148
Q

Where do lungs arise from?

A

the lung bud

149
Q

What germ layer do the lungs derive from?

A

endoderm (adjacent to foregut)

150
Q

When do the lungs form?

A

in the 4th week of development

151
Q

When do the separate lungs form?

A

lung bud splits into 2 at the end of the 4th week, progressively branching during development

152
Q

What germ layer do the gonads derive from?

A

mesoderm

153
Q

What is the first stage of development of gonads?

A

bipotential structures known as gonadal/genital ridges

154
Q

What happens in the further development of gonads if the embryo is XY?

A 
- presence of XY gene on Y chromosome directs gonadal cells to become sertoli cells
triggering:
- Leydig cell formation
- testis development 
- testosterone production
155
Q

What happens in the further development of gonads if the embryo is XX?

A
  • absence of SRY leads to gonadal cells adopting a granulosa cell fate and ovary development
  • is re-enforced by FOXL2
156
Q

What are the cohesin proteins involved in maintaining cohesion between chromatids?

A
  • REC8

- SMC2

157
Q

What characterises a complete hydatidiform mole?

A

absent fetal tissue

158
Q

What characterises a partial hydatidiform mole?

A

fetal tissue present

159
Q

What are some rare forms of Gestational Trophoblastic Neoplasias?

A
  • invasive mole

- choriocarcinoma

160
Q

What are some very rare forms of Gestational Trophoblastic Neoplasias?

A
  • Placental Site Trophoblastic Tumour (PSTT)

- Epithelioid Trophoblastic Tumour

161
Q

What does the placenta that accompanies a hydatidiform mole look like?

A

presence of grape-like villi

BRS YR2 (70 decks)

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