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Human Reproduction > Embryogenesis > Flashcards

Embryogenesis Flashcards

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
Q

When does the secondary oocyte re-enter meiosis?

A

After the cortical reaction

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26
Q

How is the sperm pronucleus formed?

A
  1. Nuclear envelope breaks down

2. Sperm protamines replaced with histones to decondense chromatin

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27
Q

How is the single diploid nucleus formed?

A
  1. Pronuclear membranes break down

2. Chromosomes become orientated on common mitotic spindle

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28
Q

What does the oocyte contribute to the zygote?

A
  1. Mitochondria
  2. Golgi apparatus
  3. Ribosomes
  4. Membrane
  5. Endoplasmic reticulum
  6. Maternal cytoplasm
  7. Centrosomes and mitotic spindles
  8. DNA
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29
Q

What does the sperm contribute to the zygote?

A
  1. DNA
  2. Centriole
  3. Small non-coding RNAs
  4. Proteins targeted for destruction once they enter the oocyte
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30
Q

Why are sperm mitochondria degraded?

A

More susceptible to mutation through oxidative stress

mtDNA not protected by histones and no DNA repair mechanisms in sperm

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31
Q

Where are sperm naturally exposed to ROS?

A
  1. Leukocytes in epididymis
  2. Transit to female tract
  3. Energetics of sperm movement
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32
Q

What is parthenogenesis?

A

Oocyte activation in absence of sperm fusion

Lacks male chromosomes and centriole

Gynogenetic diploid if polar body not expelled

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33
Q

At what point in human gestation do parthenogenetic embryos die?

A

During first cleavage as no centriole

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34
Q

What kind of development does a gynogenetic conceptus favour?

A

Embryo

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35
Q

What kind of development does an androgenetic conceptus favour?

A

Extraembryonic

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36
Q

What are imprinted genes?

A

Genes only expressed by one parental allele

Silenced by methylation on the other parental allele

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37
Q

What is a hydatidiform mole?

A

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

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38
Q

Give three examples of epigenetic modifications

A
  1. DNA methylation
  2. Histone methylation
  3. ncRNAs
39
Q

What is the effect of DNA methylation?

A

Changes conformation of DNA to prevent access of transcription factors

40
Q

Which pronucleus is more methylated at fertilisation?

A

Male

41
Q

When does DNA demethylation take place?

A

After fertilisation

42
Q

When does DNA remethylation take place?

A

Blastocyst stage

43
Q

Which loci are resistant to demethylation?

A

Imprinted loci

44
Q

What are imprinted genes important for?

A
  1. Placenta development

2. Reproductive behaviour

45
Q

What is the conflict theory?

A

Paternal genes drive growth of placenta whilst maternal genes constrain fetal growth to prevent nutrient depletion and facilitate delivery

46
Q

What is the morula?

A

First cleavage divisions

~8-16 cells

Cells are totipotent

Cells can be removed for genetic diagnosis

47
Q

What is maternal cytoplasmic inheritance?

A

First cell division under influence of maternal mRNA and proteins generated in oocyte during folliculogenesis

48
Q

When is transcription of embryonic genome initiated?

A

4-8 cell stage

49
Q

Until what point does maternal RNA persist?

A

Blastocyst stage

50
Q

What is compaction?

A
  1. Creating cell polarity

2. Initiating cell specialisation

51
Q

Where is concanavalin A expressed?

A

Junctions between cells of morula

52
Q

How is the blastocoel formed?

A

Establishment of ion gradients causes influx of water

53
Q

What does the blastocyst consist of?

A

Trophectoderm and inner cell mass

54
Q

What is the trophectoderm?

A

Trophoblast contributes to formation of placenta

55
Q

What is the inner cell mass?

A

Forms embryo and contributes mesoderm to placenta

56
Q

At what stage of development does the embryo implant?

A

Blastocyst stage

57
Q

What are Cdx2 and Oct4

A

Transcription factors that determine cell fate

58
Q

What is the role of Oct4?

A

Regulates pluripotency

59
Q

What is the role of Cdx2?

A

Trophoblast lineage determinant

60
Q

Where is Oct4 expressed?

A

8-cell stage: nuclei of all blastomeres

Blastocyst stage: inner cell mass

61
Q

Where is Cdx2 expressed?

A

8-cell stage: nuclei of all blastomeres

Blastocyst stage: trophoblast

62
Q

What regulates Cdx2 expression?

A

Degree of cell-cell contact

Activated by Yap and Tead4

63
Q

What is hippo?

A

A kinase

Active in non-polarised cells

Phosphorylates Yap, preventing it from entering the nucleus - inhibits Cdx2 expression

64
Q

After how many days does conceptus enter uterus?

A

3.5 days after fertilisation

65
Q

What may be the effect of chlamydia infection?

A

Scarring and narrowing of Fallopian tube

66
Q

What is the pO2 in the Fallopian tube?

A

Low

10-30mmHg

67
Q

Where does the zygote get its nutrition from?

A
  1. Secretions from cells of oviduct

2. Then endometrial glands

68
Q

What is the source of energy for the fertilised ovum?

A

Pyruvate

69
Q

What is the source of energy at the 2-cell stage?

A

Pyruvate and lactate

70
Q

What is the source of energy at the 8-cell stage?

A

Glucose and essential amino acids

71
Q

What is the source of energy at the blastocyst stage?

A

Simple sugars

72
Q

How does the blastocyst hatch from the zona pellucida?

A

Proteases

73
Q

Where does implantation occur?

A

Near fundus of uterus

74
Q

What is placenta praevia?

A

Placenta covers cervical opening

Associated with increased risk of antepartum haemorrhage

75
Q

How does the conceptus implant into the uterus?

A

Invasive interstitial implantation

Completely embedded in uterine wall

76
Q

What does receptivity of the endometrium involve?

A
  1. Downregulation of inhibitory mechanisms

2. Upregulation of factors promoting attachment

77
Q

What is the window of implantation?

A

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
Q

Give five features of the endometrium in the pre-receptive window

A
  1. Embryotoxic
  2. High progesterone receptor expression
  3. Thick mucin glycoprotein coat
  4. Negative charge on surface membrane
  5. Long microvilli
79
Q

Give seven features of the endometrium in the receptive window

A
  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
Q

What is the effect of reduced glycosylation of MUC1?

A

Allows protein-protein interactions between blastocyst and uterine lining, leading to implantation

81
Q

Give three actions of LIF

A
  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
Q

What does invasion of endometrium involve?

A

Matrix metalloproteases

83
Q

At what point after fertilisation does implantation take place?

A

7 days

Fully embedded after 11 days

84
Q

What are decidual cells formed from?

A

Spindly stromal cells

85
Q

Give two features of decidual cells

A
  1. Large and round

2. Secrete cytokines

86
Q

What cytokines do decidual cells secrete?

A
  1. IGF-binding proteins

2. Prolactin

87
Q

What are the three regions of the decidua?

A
  1. Basalis - beneath conceptus
  2. Capsularis - over conceptus
  3. Parietalis - around the rest of the conceptus
88
Q

What is amplification?

A

Extensive decidualisation after implantation

89
Q

What is menstruation?

A

Shedding of decidual cells because they cannot de-differentiate if fertilisation does not occur

90
Q

What secretes human chorionic gonadotropin?

A

Trophoblast

91
Q

What is the role of hCG?

A
  1. Maintains corpus luteum so that it continues secreting progesterone to prevent menstruation
92
Q

How long is the corpus luteum maintained?

A

10 weeks until placenta produces sufficient progesterone

93
Q

What is the percentage of conceptuses that become live births?

A

~30%

94
Q

What is vanishing twin phenomenon?

A

One twin miscarries and the other twin resorbs it

Human Reproduction (17 decks)

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