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Embryogenesis Flashcards

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1
Q

What do oviduct epithelial cells do?

A

Bind sperm

Make them briefly immobile

Stabilise sperm after capacitation

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2
Q

When do sperm reacquire mobility?

A

Ovulation

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3
Q

How is oocyte moved to the ampulla?

A

Swept along by cilia and muscle contractions

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4
Q

Where does fertilisation take place?

A

The ampulla

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5
Q

What three events does fertilisation require?

A
  1. Activation of sperm
  2. Establishment of diploidy
  3. Activation of ovum
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6
Q

What induces sperm activation?

A
  1. Progesterone from cumulus cells

2. Binding to zona proteins on oocyte

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7
Q

What does sperm activation cause?

A
  1. Hyperactive tail movement - whiplash

2. Acrosome reaction

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8
Q

What promotes hyperactive sperm tail movement?

A

Opening of calcium channels to activate PKC

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9
Q

What is the acrosome reaction?

A
  1. Fusion of outer acrosome and sperm plasma membranes
  2. Phospholipase C and SNARE proteins involved
  3. Release of hyaluronidase and exposure of acrosin on inner acrosome membrane
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10
Q

What are the zona pellucida proteins?

A

Glycoproteins

ZP1-4

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11
Q

What do ZP1, ZP3 and ZP4 do?

A
  1. Bind capacitated sperm

2. Induce acrosome reaction

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12
Q

What pathway does ZP3 activate?

A

Gi protein-coupled receptors on sperm

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13
Q

What does ZP2 do?

A

Weakly binds capacitated sperm to allow progression through zona

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14
Q

What allows sperm to burrow through zona pellucida?

A
  1. Acrosin - protease

2. Physical movement

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15
Q

What space does sperm enter once it penetrates zona?

A

Perivitelline space

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16
Q

Where does membrane fusion occur in the mouse?

A

Equatorial region away from female pronucleus

Enveloped by microvilli

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17
Q

What does the microvillus-free area of the oocyte signify?

A

Position of female pronucleus

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18
Q

What are the three proteins essential for binding?

A
  1. Izumo1 (sperm)
  2. Juno
  3. CD9
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19
Q

What is Izumo1?

A

Ligand on sperm essential for binding

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20
Q

What is Juno?

A

Izumo1 receptor on oocyte

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21
Q

What is CD9?

A

Tetraspanin on oocyte

Binding partner for Juno

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22
Q

What is syngamy?

A

Combining of chromosomes

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23
Q

How is the oocyte activated?

A
  1. Wave of calcium release across oocyte from site of sperm fusion
  2. Initiated by PLCζ enzyme from sperm
  3. Helps to prevent polyspermy
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24
Q

What is the cortical reaction?

A

Release of cortical granules stimulated by calcium waves

Fill perivitelline space

Ovastatin cleaves binding sites on ZP3/4 and ZP2 so that sperm can no longer bind

Zona proteins become cross-linked

Juno receptor exocytosed

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25
When does the secondary oocyte re-enter meiosis?
After the cortical reaction
26
How is the sperm pronucleus formed?
1. Nuclear envelope breaks down | 2. Sperm protamines replaced with histones to decondense chromatin
27
How is the single diploid nucleus formed?
1. Pronuclear membranes break down | 2. Chromosomes become orientated on common mitotic spindle
28
What does the oocyte contribute to the zygote?
1. Mitochondria 2. Golgi apparatus 3. Ribosomes 4. Membrane 5. Endoplasmic reticulum 6. Maternal cytoplasm 7. Centrosomes and mitotic spindles 8. DNA
29
What does the sperm contribute to the zygote?
1. DNA 2. Centriole 3. Small non-coding RNAs 4. Proteins targeted for destruction once they enter the oocyte
30
Why are sperm mitochondria degraded?
More susceptible to mutation through oxidative stress mtDNA not protected by histones and no DNA repair mechanisms in sperm
31
Where are sperm naturally exposed to ROS?
1. Leukocytes in epididymis 2. Transit to female tract 3. Energetics of sperm movement
32
What is parthenogenesis?
Oocyte activation in absence of sperm fusion Lacks male chromosomes and centriole Gynogenetic diploid if polar body not expelled
33
At what point in human gestation do parthenogenetic embryos die?
During first cleavage as no centriole
34
What kind of development does a gynogenetic conceptus favour?
Embryo
35
What kind of development does an androgenetic conceptus favour?
Extraembryonic
36
What are imprinted genes?
Genes only expressed by one parental allele Silenced by methylation on the other parental allele
37
What is a hydatidiform mole?
All chromosomes of paternal origin due to loss of female pronucleus and duplication of male pronucleus Absence of fetal tissue and overgrowth of placental tissues Placental villi are oedematous
38
Give three examples of epigenetic modifications
1. DNA methylation 2. Histone methylation 3. ncRNAs
39
What is the effect of DNA methylation?
Changes conformation of DNA to prevent access of transcription factors
40
Which pronucleus is more methylated at fertilisation?
Male
41
When does DNA demethylation take place?
After fertilisation
42
When does DNA remethylation take place?
Blastocyst stage
43
Which loci are resistant to demethylation?
Imprinted loci
44
What are imprinted genes important for?
1. Placenta development | 2. Reproductive behaviour
45
What is the conflict theory?
Paternal genes drive growth of placenta whilst maternal genes constrain fetal growth to prevent nutrient depletion and facilitate delivery
46
What is the morula?
First cleavage divisions ~8-16 cells Cells are totipotent Cells can be removed for genetic diagnosis
47
What is maternal cytoplasmic inheritance?
First cell division under influence of maternal mRNA and proteins generated in oocyte during folliculogenesis
48
When is transcription of embryonic genome initiated?
4-8 cell stage
49
Until what point does maternal RNA persist?
Blastocyst stage
50
What is compaction?
1. Creating cell polarity | 2. Initiating cell specialisation
51
Where is concanavalin A expressed?
Junctions between cells of morula
52
How is the blastocoel formed?
Establishment of ion gradients causes influx of water
53
What does the blastocyst consist of?
Trophectoderm and inner cell mass
54
What is the trophectoderm?
Trophoblast contributes to formation of placenta
55
What is the inner cell mass?
Forms embryo and contributes mesoderm to placenta
56
At what stage of development does the embryo implant?
Blastocyst stage
57
What are Cdx2 and Oct4
Transcription factors that determine cell fate
58
What is the role of Oct4?
Regulates pluripotency
59
What is the role of Cdx2?
Trophoblast lineage determinant
60
Where is Oct4 expressed?
8-cell stage: nuclei of all blastomeres | Blastocyst stage: inner cell mass
61
Where is Cdx2 expressed?
8-cell stage: nuclei of all blastomeres | Blastocyst stage: trophoblast
62
What regulates Cdx2 expression?
Degree of cell-cell contact Activated by Yap and Tead4
63
What is hippo?
A kinase Active in non-polarised cells Phosphorylates Yap, preventing it from entering the nucleus - inhibits Cdx2 expression
64
After how many days does conceptus enter uterus?
3.5 days after fertilisation
65
What may be the effect of chlamydia infection?
Scarring and narrowing of Fallopian tube
66
What is the pO2 in the Fallopian tube?
Low 10-30mmHg
67
Where does the zygote get its nutrition from?
1. Secretions from cells of oviduct | 2. Then endometrial glands
68
What is the source of energy for the fertilised ovum?
Pyruvate
69
What is the source of energy at the 2-cell stage?
Pyruvate and lactate
70
What is the source of energy at the 8-cell stage?
Glucose and essential amino acids
71
What is the source of energy at the blastocyst stage?
Simple sugars
72
How does the blastocyst hatch from the zona pellucida?
Proteases
73
Where does implantation occur?
Near fundus of uterus
74
What is placenta praevia?
Placenta covers cervical opening Associated with increased risk of antepartum haemorrhage
75
How does the conceptus implant into the uterus?
Invasive interstitial implantation Completely embedded in uterine wall
76
What does receptivity of the endometrium involve?
1. Downregulation of inhibitory mechanisms | 2. Upregulation of factors promoting attachment
77
What is the window of implantation?
Period of progesterone dominance Progesterone and oestrogen ready the uterus for implantation Oestrogen prepares the conceptus for implantation Burst of oestrogen synthesis required for implantation
78
Give five features of the endometrium in the pre-receptive window
1. Embryotoxic 2. High progesterone receptor expression 3. Thick mucin glycoprotein coat 4. Negative charge on surface membrane 5. Long microvilli
79
Give seven features of the endometrium in the receptive window
1. Safe for embryos to implant 2. Progesterone receptors decrease 3. Thinner mucin glycoprotein coat 4. Loss of negative charge on surface membrane 5. Pinopodes to absorb uterine fluid 6. LIF-dependent 7. Shorter/absent microvilli
80
What is the effect of reduced glycosylation of MUC1?
Allows protein-protein interactions between blastocyst and uterine lining, leading to implantation
81
Give three actions of LIF
1. Acts on trophoblast and uterine lining 2. Leads to upregulation of HB-EGF on uterine epithelium 3. Induces uterine α2 expression, and trophoblast integrins α6 and β5 expression
82
What does invasion of endometrium involve?
Matrix metalloproteases
83
At what point after fertilisation does implantation take place?
7 days Fully embedded after 11 days
84
What are decidual cells formed from?
Spindly stromal cells
85
Give two features of decidual cells
1. Large and round | 2. Secrete cytokines
86
What cytokines do decidual cells secrete?
1. IGF-binding proteins | 2. Prolactin
87
What are the three regions of the decidua?
1. Basalis - beneath conceptus 2. Capsularis - over conceptus 3. Parietalis - around the rest of the conceptus
88
What is amplification?
Extensive decidualisation after implantation
89
What is menstruation?
Shedding of decidual cells because they cannot de-differentiate if fertilisation does not occur
90
What secretes human chorionic gonadotropin?
Trophoblast
91
What is the role of hCG?
1. Maintains corpus luteum so that it continues secreting progesterone to prevent menstruation
92
How long is the corpus luteum maintained?
10 weeks until placenta produces sufficient progesterone
93
What is the percentage of conceptuses that become live births?
~30%
94
What is vanishing twin phenomenon?
One twin miscarries and the other twin resorbs it

Human Reproduction (17 decks)

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