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Reproductive and Developmental Biology > Lecture 7 - Implantation and Placentation > Flashcards

Lecture 7 - Implantation and Placentation Flashcards

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1
Q

The early conceptus

A

from zygote to hatched blastocyst

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2
Q

Fertilized oocyte

A

ovum

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3
Q

-cyte at end of germ cell says

A

it’s haploid

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4
Q

-ium at end of germ cell says

A

diploid

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5
Q
A
  • polar body (finished meiosis because fertilized, extra DNA) on the left, inside
  • it’s been fertilized = 2n but not yet diploid nucleus
    • male and female pro nuclei that haven’t fused
  • ovum has 2 pro-nuclei
  • fuzzy bit around the outside = zona pellucida
    • still around oocyte even though fertilized
    • hardens as block to polyspermy
  • at edges of zona are cumulus cells that haven’t left yet
  • eg at bottom
  • 2 pro nuclei in center – once fuse get proper diploid cell, get mitosis
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6
Q

Zona pellucida

A
  • hardens to block polyspermy
  • cumulus cells at the edges
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7
Q

Once the 2 pro-nuclei fuse

A

get a proper diploid cell, mitosis

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8
Q

At the 2, 4, 8 cell conceptus

A
  • zona pellucida still there so can’t grow
  • when cells divide they’re smaller because restricted by zona pellucida unless stretch
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9
Q

The morula

A
  • zona starts to thin, start to get expansion of the “embryo” inside
  • embryonic growth - not yet an embryo
  • every cell (blastomere) in there is totipotent
    • can become anything
    • takeo ne out and not influence what’s left behind (totipotent will divide and replace it)
    • (pluripotent = many, has the potential to become several things)
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10
Q

Blastomeres in the morula are

A

totipotent

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11
Q

What is the function of the zona pellucida?

A
  • hardens to stop polyspermy
  • keeps the cells together
  • once this has a good structure can lose the zona
  • most mammals are polytocus
    • several embryos without zona around each = may mix
    • end up with chimeric, with blastomeres from one embryo to the other
  • zona prevents embryonic chimerism
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12
Q

Blastocyst

(picture)

A
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13
Q

Blastocyst

A
  • if a bowl of cells is dividing, will reach point where the sphere is bigger than the exponential series
  • a cavity will open up in the middle = blastocoel
  • this is now a blastocyst with cyst being a fluid-filled structure
    • growing cyst
  • see differentiation
    • eg morula totipotent will cells identical
  • cells areound the outside is trophoblast
    • tropho indicating growth
    • = growing sphere
  • pluriblast (inner cell mass ICM)
    • pluriblast makes up the embryo
    • so trophoblast goes on to make the placenta (contributes to)
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14
Q

Morula (b) vs. Blastocyst (e)

(picture)

A
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15
Q

Morula v Blastocyst

A
  • morula has identical blastomeres
    • totipotent - each one can make an embryo
  • blastocyst is a fluid-filled cavity, outside is trophoblast
    • cells don’t look the same
    • trophoblast has villi
      • later for attachment
  • pluriblast gives rise to layers of the embryo
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16
Q

Blastocyst derivatives

(picture)

A
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17
Q

Blastocyst has

A
  • trophoblast on the outside
  • pluriblast on the inside (inner cell mass)

(blastocyst → trophoblast and pluriblast

trophoblast → cytotrophoblast and syncytiotrophoblast

pluriblast → hypoblast and epiblast)

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18
Q

Trophoblast divided into

A

cytotrophoblast and syncytiotrophoblast

(blastocyst → trophoblast and pluriblast

trophoblast → cytotrophoblast and syncytiotrophoblast

pluriblast → hypoblast and epiblast)

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19
Q

Cytotrophoblast

A
  • individual trophoblast cells

(blastocyst → trophoblast and pluriblast

trophoblast → cytotrophoblast and syncytiotrophoblast

pluriblast → hypoblast and epiblast)

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20
Q

Syncytiotrophoblast

A
  • fused cells
  • individual cytotrophoblast cells fuse to give syncytium (large multinucleate cell)
  • placenta with 1 cell covering the whole thing

(blastocyst → trophoblast and pluriblast

trophoblast → cytotrophoblast and syncytiotrophoblast

pluriblast → hypoblast and epiblast)

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21
Q

Together the cytotrophoblast and the syncytiotrophoblast contribute to the

A

chorion

(placental membrane)

(blastocyst → trophoblast and pluriblast

trophoblast → cytotrophoblast and syncytiotrophoblast

pluriblast → hypoblast and epiblast)

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22
Q

Pluriblast can be divided into

A

hypoblast (small growing cells) and epiblast (the ones on the outside)

(blastocyst → trophoblast and pluriblast

trophoblast → cytotrophoblast and syncytiotrophoblast

pluriblast → hypoblast and epiblast)

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23
Q

Hypoblast

A

goes on to form the yolk sac

(blastocyst → trophoblast and pluriblast

trophoblast → cytotrophoblast and syncytiotrophoblast

pluriblast → hypoblast and epiblast)

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24
Q

Epiblast

A

gives layers of our embryo (endo meso ectoderm)

  • will also give rise to ectoderm and extraembryonic mesoderm
  • amniotic tissue around ICM
  • extraembryonic tissue around the trophoblast

(blastocyst → trophoblast and pluriblast

trophoblast → cytotrophoblast and syncytiotrophoblast

pluriblast → hypoblast and epiblast)

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25
Q

The amniotic ectoderm and the extraembryonic mesoderm form

A

the amnion

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26
Q

The endoderm produces

A

allantois

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27
Q

Blastocyst hatching

(picture)

A
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28
Q

Blastocyst hatching

A
  • has to hatch to leave zona pellucida behind
  • the blato needs to hatch to be able to attach
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29
Q

Embryo attachment

(picture)

A
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30
Q

Embryo attachment

A
  • apposition - the embryo physically touches endometrium
    • is reversible
  • adhesion then irreversible
  • can then invade
  • compares apposition adhesion invasion in atherosclerosis (WBC through clogged artery)
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31
Q

Embryo attachment

2 phases

A
  • apposition
    • reversible
    • coming together with endometrium
  • followed by adhesion/adherence
    • stickiness
  • molecular mechanisms differ between species and include redundancy (several molecules fulfill the same functions)
    • redundant because it’s not allowed to go wrong
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32
Q

Embryo attachment

need to down-regulate

A

endometrial molecules which would block/deter adherence

  • can repel or attract embryo
  • so need to get rid of anything to deter embryo
  • eg MUC1 gets in the way so must get rid of it
  • has sugars attached through serine and threonine residues
  • eg MUC1
    • encodes O-linked glycoprotein
      • up-regulated by progesterone
      • down-regulated by blastocyst
  • gets rid of protective layer
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33
Q

Embryo attachment

need to up-regulate molecules which facilitate

A

adherence (/attraction)

eg LIF1

  • estrogen-induced cytokine with paracrine roles in
    • decidualization of endometrium
      • change in endometrium that makes it ready for the embryo
    • up-regulation of EGF family
  • differences in mammals but MUC1 important and LIF1 important, also need upregulation of EGF family
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34
Q

Embryo attachment

EGF family members include

A

heparine-binding EGF-like growth factor (HB-EGF)

  • activates EGF receptors plus heparine sulphage glycoproteins (HSPG) on TB to dissolve ZP
  • HB-EGF responsible through EGF receptors for dissolving zona pellucida
  • here blastocyst needs to hatch before attaches to endometrium
  • upregulate LIF1 then this to dissolve zona pellucida so embryo can hatch
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35
Q

Embryo attachment

other proteins implicated in embryo apposition include

A
  • integrins (on the TB)
    • bind selectins on endometrium cells
  • selectins (on the endometrium)
  • ECM molecules (eg laminin, fibronectin, collagen)
    • for binding
  • trophinin-bystatin-tastin complex
    • specific complex for embryo attachment
  • Frizzled-Notch interactions
    • Frizzled is the ligand
  • each of these pairs will cause to stick but have each of these to make sure they stick/implant
  • majority (80%) of embryos don’t pass here, even with this redundancy
36
Q

Timing of embryonic events

A

(post ovulation)

  • conceptus enters uterus at 3 days
  • 3-4.5 days to form blatocyst
  • moust, rat as soon as it forms in tattaches
  • all within a week of ovulation the embryo is attached (not necessarily implanted)
  • time to form blastocyst is slightly slower
  • attachment is longer for embryo to attach (free-flating in uterine cavity)
  • becuase not attached - how does it get nourishment
  • normally go for nearest blood vessel but doesn’t here - floats for a bit
37
Q

Embryo implantation

blastocyst implantation can be

A
  • invasive
  • non-invasive
38
Q

Invasive blastocyst implantation

A

breach endometrial epithelium to invade the underlying stroma

(eg primates, carnivores, and rodents)

39
Q

Non-invasive blastocyst implantation

A

endometrial epithelium intact (or locally disrupted)

(eg ungulates)

40
Q

Invasive vs non-invasive embryo implantation

A
  • invasive = blastocyst breaches the endometrium epithelium into the endometrial wall
  • non-invasive = attaches and stays on surface of uterus (local disruption but not invasive)
41
Q

Non-invasive implantation

A
  • blastocyst grows rapidly (extraembryonic growth
  • maximizes surface area to absorb uterine nutrients
  • eg pig blastocyst elongates x50 (2 to 100 mm) on day 6 to day 12 pc
  • embryo-maternal interfacea cross epithelium (caruncles-cotyledons)
    • embryos not through the epithelium but sit on the surface
    • cotyledon on embryo
    • caruncle on endometrium
    • sit together but never breach each other
  • blastocyst has 2 cell populations
    • trophoblast around grows quicly to give maximum surface area
    • free-floating must absorb nutrients across the surface
42
Q

Invasive implantation

A
  • blatocyst implants while small (extraembryonic growth)
  • trophoblast invades between epithelium into underlying stroma, but embryo part stays really small
  • depth of invasion limited by speed of stromal/decidual response - poor decidual response triggers deeper invasion
  • the blastocyst can’t grow until it hooks up to a blood supply (ass opposed to above feeding off uterine secretions)
  • stroma undergoes decidualization (quality of response decides how well it invades
    • good decidual response = doesn’t need to invade very far
    • poor decidual response = embryo keeps burrowing down through the endometrium until it hooks up to a blood vessel
43
Q

Invasive implantation

blastocyst

A
  • blastocyst with external trophoblast, internal cavity, pluriblast/inner cell mass to go on to give the embryo proper
  • the blastocyst with trophoblast around the outside with villa with zona in the way to stop embryo to binding before it gets to the uterus
    • without you get ectopic pregnancy - anywhere other than uterus
  • trophoblast then interdigitates
44
Q

Invasive implantation appears to be

A

an inflammatory cascade

  • up-regulation of MMPs and, simultaneously, of TIMPs
    • MMPs break down extracellular matrix
    • TIMPs = tissue inhibitors
    • upregulate MMPs and inhibitors to control
  • increased PGs (via PTGS/COX-2)
  • positive effect on human implantation of endometrial scratching
45
Q

Endometrial scratching

A

(invasive implantation)

  • cause inflammation in women who are having trouble conceiving
    • not all women
    • this technique of scratching the endometrium before putting the embryos back doesn’t work for all women
    • if look just at women who have miscarriage or repeated pregnancy failure – scratch their endometrium and replace embryos the chances of conceiving go up massively
    • problem with the inflammation so have to mechanically cause inflammation before put embryo in
    • so inflammatory cascade is required for embryo attachment and implantation, even if you have to cause it
46
Q

Decidualization

A
  • mother provides deciduon - endometrium which responds to the embryo being there
    • in decidualization whent he conceptus attaches we see in the underlying stroma (myometriuim doesn’t change):
  • rapid changes in endometiral stroma underlying the conceptus, including
    • increased vascular permeability
    • oedema
    • losening of the ECM between cells
    • stromal cell differentiation
47
Q

Decidualization

inflammatory cascade mediated by:

A
  • increased prostaglandins
  • pro-inflammatory cytokines
    • eg IL-11 (doesn’t normally appear on list)
  • VEGFs
    • vascular endothelial growth factor - want more blood vessels
  • angiopoietins
    • about angiogenesis
    • the tissue will become highly vascularized to form a placenta
  • prolactin-related peptides
    • eg proliferin
    • for tissue growth, but wouldn’t have expected to be there (expect inflammatory mediators)
48
Q

Decidualization

up-regulation of

A

11βHSD1 enzyme

  • makes cortisol from cortisone
  • generates active cortisol from intert cortisone
  • hydroxyl group gives cortisol its name (the alcohol cortisol needs to be active)
  • increases cortisone around
  • cortisol active, cortisone inert
  • cortisol to cortisone switches the enzyme off completely
  • in decidualization as the endometrial cells decidualize upregulate the enzyme that does the opposite
    • turns cortisone into cortisol to increase the amount of cortisol
  • upregulate MMPs as well as TIMPs to keep MMPs under control
  • here want prostaglandins and inflammatory cascade but don’t want to go too far (only localized) so upregulate machiner to make anti-inflammatory steroid
49
Q

Decidaulization

rodents

A
  • induced by presence of embryo
  • primary (local) followed by secondary (widespread) decidualization reactions
  • rodents only decidualize if there’s an embryo there
    • normal rat/mouse think anything in its uterus must be an embryo
    • respond to something in uterus not necessarily embryo
    • get primary then secondary just because “embryo” there
50
Q

Decidualization

primates

A
  • occurs spontaneously in response to progesterone
    • where from?
    • progesterone from gland corpus luteum
      • most species polytocus so have several corpa lutea which make progestrone to make the endometrium
  • decidualization every month (assumes an embryo is there) and so prepares for pregnancy
  • in some species the deciduon only forms in the event of pregnancy (rodents)
  • in others deciduize every month assuming a pregnancy should be there
51
Q

Placental classification

Classify mammalian placenta on the basis of

A

extent/shape of placenta

52
Q

Placental classification

types

A
  • discoid
  • zonary
  • cotyledonary
  • diffuse
53
Q

Discoid placentas

A

also bidiscoid

distinct disc on particular region of implanting blastocyst to become embryo

  • primates
  • lagomorphs
  • rodents
  • insectivores
  • bats
54
Q

Zonary placentas

A

placentas in a discrete zone

  • carnivores
  • seals
  • elephants
55
Q

Cotyledonary

A
  • sheep
  • cows
  • giraffes
  • deers
  • goats
56
Q

Diffuse placentas

A
  • general contact between embryo and reproductive tract
  • diffuse foci but lots of them between the embryo and the endometrium
  • prosimians (discoid shape is late evolution in primates, primate ancestors still have diffuse)
  • pigs
  • horses
  • camels
  • moles
  • cetaceans
  • kangaroo
57
Q
A
  • discoid
  • entire conceptus trophoblast everywhere
  • special piece of trophoblast interacts with deciduon and forms the placental disc which is then delivered as afterbirth
58
Q
A
  • zonary
  • carnivores
  • coceptus still elliptical
  • just a single zone like a belt to form the placenta
59
Q
A
  • cotyledonary
  • gray is conceptus (embyo)
  • purple is contact point with uterus
  • cotyledon meets with coruncles to bind on endometrium
60
Q
A
  • diffuse
  • lots of points of contact
  • not even distinct cotyledons
61
Q

Classify mammalina placenta on the basis of

A

maternal tissue in contact with the conceptus

62
Q

Placental classification

classify mammalian placenta on the basis of maternal tissue in contact with the conceptus

A
  • blood (maternal tissuue that contacts is blood)
    • eg primates, lagomorphs, rodents
  • capillary endothelium
    • eg carnivores with zonary have capillary endothelium
    • endothelial cells from mom’s capillaries between her blood flow and fetal blood flow
  • endometrial epithelium
    • eg sheep and cows
    • non-invasive placentation
    • fetal tissue not in touch with blood or vessels but endometrium and endothelium
  • epithelial syncytium (eg pics and horses)
    • fusion of cells between mother’s epithelium and binucleate cells (special trophoblast cells that come out from the fetus)
    • syncytium between mom’s epithelium and fetus’s binucleate cells
63
Q
A

a - haemachorial

d - endotheliochorial

e - epitheliochorial

f - synepitheliochorial

64
Q

Haemochorial

(picture)

A
65
Q

Haemochorial placenta

A
  • chorion bathed directly with blood
  • haemochorial placentation
    • involves blood and chorion
66
Q

Chorion

A

(fetal/embryonic membrane derived partly from the mesoderm - especially the trophoblast and cytotrophoblast and syncytiotrophoblast together)

67
Q
A

endotheliochorial

68
Q

Endotheliochorial placenta

A
  • chorion separated from blood by mom’s endothelial cells
  • capillary endothelium doesn’t break down
  • seen in carnivores, seals, elephants
69
Q

Epitheliochorial (picture)

A
70
Q

Epitheliochorial placenta

A
  • conceptus has choirion around it but maternal epithelium still intact because noninvasive placentation
71
Q

Synepitheliochorial

(picture)

A
72
Q

Synepitheliochorial placenta

A
  • epithelium fuses with binucleate cells out from chorion (chorion tropholastic cells) to get synepithelio-chorial
73
Q

Placental classification

classify mammalian placenta on the basis of

A

number of layers in chorionic trophoblast

  • how many layers of chorion are there in the trophoblast between the embryo which needs the nutrients and the mother
  • layers of chorion to be traversed by anything going into/out of the embryo
  • layers of chorion between maternal and embryonic circulation
  • 1 (eg primates, carnivores, pigs, horses)
  • 2 (eg lagomorphs)
  • 3 (eg rodents)
74
Q

Three layers of placental classification

A
  1. extent/shape of placenta
  2. maternal tissue in contact with the conceptus
  3. number of layers in the chorionic trophoblast
75
Q

Haemochorial placentae

primates =

A

haemomonochorial placenta

76
Q

Haemochorial placentae

lagomorphs =

A

haemodichorial placenta

77
Q

Hameochorial placentae

rodents =

A

haemotrichorial placenta

78
Q

Haemochorial placentae

A
  • primates = haemomonochorial placenta
  • lagomorphs = haemodichorial placenta
  • rodents = haemotrichorial placenta
79
Q

Epitheliochorial placentae

pig/horse =

A

diffuse epitheliochorial placenta

80
Q

Epitheliochorial placentae

sheep/cows =

A

cotyledonary synepitheliochorial placenta

(syncytium between endometrial epithelium and fetal binucleate cells)

81
Q

Haemochorial placentae can be

A

mono-

di-

tri-

-chorial

82
Q

Epithelio placentae

A

non-invasive

chorion fuses with epithelium from mother

diffuse placentae and cotyledonary placentae

83
Q

Epitheliochorial placentae

pig/horse =

A

diffuse epitheliochorial placenta

84
Q

Epitheliochorial placentae

sheep/cow =

A

cotyledonary synepitheliochorial

(syncytium between endometrial epithelium and fetan binucleate cells)

85
Q

Placentome

A

placenta only contacts at a discrete point

86
Q

Diffuse vs Cotyledonary

A
  • cotyledonary - really distinct areas with defined structure with contact between placenta/embryo and mother
  • diffuse - light contact points all the way over the conceptus
87
Q
A

Reproductive and Developmental Biology (8 decks)

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