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Developmental Origins of Health and Disease Flashcards

1
Q

Define

Non-communicable disease (NCD)

A

diseases that cannot be passed from person-to-person and include heart disease, stroke, cancer, diabetes and chronic lung disease, are collectively responsible for almost 70% of all deaths worldwide.

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2
Q

Define

Developmental Origins of Health and Disease (DOHaD) Hypothesis

A

postulates that exposure to certain environmental influences during critical periods of development and growth may have significant consequences on an individual’s short- and long-term health

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3
Q

Define

Metanephroi

A

The most caudally located of the three excretory organs appearing in the evolution of the vertebrates (the others being the pronephros and the mesonephros); in mammalian embryos, it develops caudal to the mesonephros during its regression, becoming the permanent kidney.

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4
Q

Define

Nephrogenesis

A

describes the embryologic origins of the kidney, a major organ in the urinary system

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5
Q

Define

Brenner Hypothesis

A

states that individuals with a congenital reduction in nephron number have a much greater likelihood of developing adult hypertension and subsequent renal failure

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6
Q

Define

Barker Hypothesis

A

Adverse conditions in pregnancy can impair fetal growth and/or promote disproportionate fetal growth (some organ do well, others don’t). While these adaptations during fetal development may promote survival of the fetus, they may also lead to limited physiological function and disease in the long term

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7
Q

Define

Nephrons

A

a filtering unit in kidneys that are made up of glomeruli and tubules

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8
Q

Define

Glomeruli

A

a network of small blood vessels (capillaries) known as a tuft, located at the beginning of a nephron in the kidney

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9
Q

Define

Pronephroi

A

the first in a sequence of kidneys that form in vertebrate embryos

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10
Q

Define

Mesonephroi

A

the excretory organ of the embryo, arising caudad to the pronephros and using its duct.

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11
Q

Define

Ureteric bud

A

a protrusion from the mesonephric duct during the development of the urinary and reproductive organs. It later develops into a conduit for urine drainage from the kidneys, which, in contrast, originate from the metanephric blastema

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12
Q

Define

Metanephric mesenchyme (MM)

A

one of the two embryonic structures that give rise to the kidney. The other structure is the ureteric bud. It is comprised of mesenchymal cells situated adjacent to the tips of the branching ureteric bud.

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13
Q

Define

Pertuburations

A

an alteration of the function of a biological system by external or internal means such as environmental stimuli, drug inhibition, and gene knockdown

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14
Q

Define

Hypertension

A

high blood pressure

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15
Q

Define

Chronic Kidney Disease (CKD)

A

a condition characterized by a gradual loss of kidney function over time

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16
Q

Definition

diseases that cannot be passed from person-to-person and include heart disease, stroke, cancer, diabetes and chronic lung disease, are collectively responsible for almost 70% of all deaths worldwide.

A

Non-communicable disease (NCD)

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17
Q

Definition

postulates that exposure to certain environmental influences during critical periods of development and growth may have significant consequences on an individual’s short- and long-term health

A

Developmental Origins of Health and Disease (DOHaD) Hypothesis

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18
Q

Definition

The most caudally located of the three excretory organs appearing in the evolution of the vertebrates (the others being the pronephros and the mesonephros); in mammalian embryos, it develops caudal to the mesonephros during its regression, becoming the permanent kidney.

A

Metanephroi

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19
Q

Definition

describes the embryologic origins of the kidney, a major organ in the urinary system

A

Nephrogenesis

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20
Q

Definition

states that individuals with a congenital reduction in nephron number have a much greater likelihood of developing adult hypertension and subsequent renal failure

A

Brenner Hypothesis

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21
Q

Definition

Adverse conditions in pregnancy can impair fetal growth and/or promote disproportionate fetal growth (some organ do well, others don’t). While these adaptations during fetal development may promote survival of the fetus, they may also lead to limited physiological function and disease in the long term

A

Barker Hypothesis

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22
Q

Definition

a filtering unit in kidneys that are made up of glomeruli and tubules

A

Nephrons

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23
Q

Definition

a network of small blood vessels (capillaries) known as a tuft, located at the beginning of a nephron in the kidney

A

Glomeruli

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24
Q

Definition

the first in a sequence of kidneys that form in vertebrate embryos

A

Pronephroi

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25
Q

Definition

the excretory organ of the embryo, arising caudad to the pronephros and using its duct.

A

Mesonephroi

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26
Q

Definition

a protrusion from the mesonephric duct during the development of the urinary and reproductive organs. It later develops into a conduit for urine drainage from the kidneys, which, in contrast, originate from the metanephric blastema

A

Ureteric bud

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27
Q

Definition

one of the two embryonic structures that give rise to the kidney. The other structure is the ureteric bud. It is comprised of mesenchymal cells situated adjacent to the tips of the branching ureteric bud.

A

Metanephric mesenchyme (MM)

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28
Q

Definition

an alteration of the function of a biological system by external or internal means such as environmental stimuli, drug inhibition, and gene knockdown

A

Pertuburations

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29
Q

Definition

high blood pressure

A

Hypertension

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30
Q

Definition

a condition characterized by a gradual loss of kidney function over time

A

Chronic Kidney Disease (CKD)

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31
Q

What diseases are considered to be non-communicable?

A

Cardiovascular disease

Cancer

Chronic respiratory diseases

Chronic kidney disease

Diabetes

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32
Q

What are some examples of modifiable behavioural risk factors of chronic disease?

A

Tobacco

Physical inactivity

Unhealthy diet

Alcohol

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33
Q

What are some examples of metabolic/physiological risk factors of chronic disease?

A

Raised blood pressure

Overweight/obesity

Hyperglycaemia (high blood glucose levels)

Hyperlipidaemia (high levels of fats in the blood)

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34
Q

Do poor living conditions in childhood and adolescence increase risk for arteriosclerotic heart disease?

A

Strong relationships between infant mortality rates in late19th and early 20th centuries and adult CVD 40-70 years later (Norway).

Conclusion: Growing up in poverty caused ‘permanent damage’, perhaps due to a ‘nutritional deficit’, which resulted in ‘life -long vulnerability’ to an affluent adult lifestyle

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35
Q

True or False:

Birth weight has considerable predictive ability for increased risk of disease in adult life

A

True

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36
Q

During the Dutch Hunger Winter, individual exposed to famine in early gestation had what? What about those exposed in late gestation?

A

Early gestation had

  • atherogenic plasma lipid profile
  • central obesity
  • increased risk of coronary heart disease

Late gestation had

  • impaired glucose tolerance
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37
Q

True or False:

Males are more sensitive to DOHaD than females

A

True

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38
Q

What are the three pairs of excretory organs developed by mammals?

A
  1. Pronephroi
  2. Mesonephroi
  3. Metanephroi
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39
Q

Which of the three pairs of excretory organs developed by mammals is the permanent kidney?

A

Metanephroi

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40
Q

How does the metanephroi develop?

A
  • Ureteric bud makes contact with the metanephric mesenchyme at around day 32 and branches.
  • Fetal kidney begins to produce urine around 10 weeks of gestation.
  • Nephrogenesis ceases at approx. 36 weeks of gestation.
  • No new nephrons form after term birth.
  • Nephrogenesis continues in babies born premature, but at a slower rate and they often finish with lower nephron number than normal
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41
Q

Signals from __________ induce branching morphogenesis. Signals from the branch (ureteric epithelial) tips induce __________.

A

Signals from metanephric mesenchyme (MM) induce branching morphogenesis. Signals from the branch (ureteric epithelial) tips induce nephrogenesis.

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42
Q

What does the ureteric bud give rise to?

A

Collecting ducts

Calyces

Pelvis

Ureter

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43
Q

What does the metanephric mesenchyme give rise to?

A
  • Nephron
    • Glomerulus (capillaries)
    • Proximal convoluted tubule
    • Loop of Henle
    • Distal convoluted tubule
  • Interstitium
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44
Q

What is renal hypoplasia/dysplasia?

A

Small/abnormal kidney

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45
Q

What is Renal Agenesis (unilateral/bilateral)?

A

Absent kidney

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46
Q

What is a Multicystic kidney?

A

Presence of multiple cysts in the kidney

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47
Q

What is a duplex kidney?

A

One ureter with a duplicated collecting system due to bifurcation of the ureter or 2 ureters.

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48
Q

What is a Vesicoureteric reflux (VUR)?

A

Backward flow of urine into the kidney

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49
Q

What is a Hydroureter?

A

Dilated ureter

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50
Q

What is Hydronephrosis?

A

Dilation of the renal pelvis

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51
Q

What is a Obstruction at vesicoureteric (VUJ) junction?

A

Obstruction at ureter-bladder junction

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52
Q

What is a Obstruction at ureteropelvic (UPJ) junction?

A

Obstruction at ureter-renal pelvis junction

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53
Q

What causes CAKUT?

A
  • Mutations, and possibly polymorphisms, of developmental genes
  • Environmental influences
    • placental blood supply
    • poor maternal/fetal nutrition
    • corticosteroids (natural, synthetic)
    • drugs (eg. gentamicin, ACE inhibitors)
    • maternal diet
    • alcohol
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54
Q

Outline the steps in the Brenner Hypothesis cycle?

A

Low nephron number

↓ filtration surface area

↓ filtered load

↑ Na+ and fluid retention

↑ ECF volume

↑Arterial pressure

↑ Glomerular capillary pressure

↑ Single nephron GFR

Glomerular hypertrophy

Glomeruloschlerosis

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55
Q

Animal models fo kidney development have shown that which factors contribute to low nephron number?

A

Calorie restriction

Protein restriction

Vitamin deficiency

Excess glucocorticoid

Placental insufficiency

Hypoxia

Antibiotic exposure

Maternal anaemia

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56
Q

How is the Barker and Brenner hypotheses linked?

A
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57
Q

Define

Epigenetics

A

the molecular mechanisms that control gene activity that enable development to occur

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58
Q

Define

Transgenerational epigenetic inheritance

A

the transmission of epigenetic markers from one organism to the next (i.e., parent–child transmission) that affects the traits of offspring without alteration of the primary structure of DNA (i.e. the sequence of nucleotides)—in other words, epigenetically

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59
Q

Define

Chromatin remodellers

A

proteins that cause the dynamic modification of chromatin architecture to allow access of condensed genomic DNA to the regulatory transcription machinery proteins, and thereby control gene expression

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60
Q

Define

Long ncRNA

A

a large and diverse class of transcribed RNA molecules with a length of more than 200 nucleotides that do not encode proteins (or lack > 100 amino acid open reading frame)

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61
Q

Define

Transferase

A

one of a class of enzymes that enact the transfer of specific functional groups (e.g. a methyl or glycosyl group) from one molecule (called the donor) to another (called the acceptor).

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62
Q

Define

Chromodomain

A

a protein structural domain of about 40–50 amino acid residues commonly found in proteins associated with the remodeling and manipulation of chromatin

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63
Q

Define

Histone deacetylases (HDACs)

A

a class of enzymes that remove acetyl groups (O=C-CH3) from an ε-N-acetyl lysine amino acid on a histone, allowing the histones to wrap the DNA more tightly

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64
Q

Define

Imprinting

A

an epigenetic phenomenon that causes genes to be expressed in a parent-of-origin-specific manner

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65
Q

Define

X inactivation

A

a process by which one of the copies of the X chromosome is inactivated in therian female mammals

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66
Q

Definition

the molecular mechanisms that control gene activity that enable development to occur

A

Epigenetics

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67
Q

Definition

the transmission of epigenetic markers from one organism to the next (i.e., parent–child transmission) that affects the traits of offspring without alteration of the primary structure of DNA (i.e. the sequence of nucleotides)—in other words, epigenetically

A

Transgenerational epigenetic inheritance

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68
Q

Definition

proteins that cause the dynamic modification of chromatin architecture to allow access of condensed genomic DNA to the regulatory transcription machinery proteins, and thereby control gene expression

A

Chromatin remodellers

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69
Q

Definition

a large and diverse class of transcribed RNA molecules with a length of more than 200 nucleotides that do not encode proteins (or lack > 100 amino acid open reading frame)

A

Long ncRNA

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70
Q

Definition

one of a class of enzymes that enact the transfer of specific functional groups (e.g. a methyl or glycosyl group) from one molecule (called the donor) to another (called the acceptor).

A

Transferase

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71
Q

Definition

a protein structural domain of about 40–50 amino acid residues commonly found in proteins associated with the remodeling and manipulation of chromatin

A

Chromodomain

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72
Q

Definition

a class of enzymes that remove acetyl groups (O=C-CH3) from an ε-N-acetyl lysine amino acid on a histone, allowing the histones to wrap the DNA more tightly

A

Histone deacetylases (HDACs)

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73
Q

Definition

an epigenetic phenomenon that causes genes to be expressed in a parent-of-origin-specific manner

A

Imprinting

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74
Q

Definition

a process by which one of the copies of the X chromosome is inactivated in therian female mammals

A

X inactivation

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75
Q

When does nephrogenesis end in humans?

A

Shortly before term birth

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76
Q

How many nephrons does the normal human kidney contain?

A

Textbooks state 1 million nephrons

In reality it is an incredibly wide range

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77
Q

True or False:

Indigenous Australians have a similar number of nephrons to White Australians

A

False

They have considerably less

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78
Q

How is birth weight related to nephron number?

A

As BW increases so does nephron number

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79
Q

What can we do now to minimise risk of hypertension and kidney disease in individuals?

A
  • Record gestational age and birthweight for all infants to identify those who are growth-restricted, preterm or LBW.
  • Growth restriction, preterm or LBW should be documented prominently in an infant’s medical record.
  • These infants should be monitored regularly for hypertension, excessive weight gain, albuminuria and hyperglycaemia.
  • Use of potentially nephrotoxic drugs (certain antibiotics, radiocontrast agents) should be minimised in these infants.
  • More resources should be allocated to enhance maternal health, fetal growth and full-term pregnancies.
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80
Q

Why is it useful to estimate Glomerular Number and Size In Vivo?

A
  • Obtain a measure of functional nephron/glomerular mass
  • Enable more accurate estimation of SNGFR – measure/estimate GFR and absolute nephron number
  • Estimate functional nephron mass in patients newly-diagnosed with CKD – baseline value.
  • Determine the effectiveness of therapy in patients with CKD – progression rates, is nephron mass stabilised or decreasing? What is happening to SNGFR?
  • Estimate nephron number in children born small or premature and identify those to monitor closely (proteinuria, blood pressure). Detect problems early and treat accordingly.
  • In animal studies, perform longitudinal studies on effects of potential new therapies on glomerular number, size and SNGFR. Powerful experimental design. Reduces numbers of animals required.
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81
Q

What is the most commonly used surrogate index of “developmental success”?

A

Birth weight

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82
Q

What is LBW associated with?

A

Low birth weight has been associated with increased risk for a large number of adult chronic diseases, including hypertension and CKD.

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83
Q

What is the specific mechanisms of epigenetics?

A

DNA (methylation)

RNA (non-coding)

Histones (modified and variant)

Chromatin remodellers

3D nuclear localisation

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84
Q

How to epigenetic mechanisms affects gene regulatory regions?

A

Epigenetic mechanisms combine to open and close gene regulatory regions

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85
Q

What are the main characteristics of epigenetic mechanisms?

A
  • Change gene activity without changing DNA sequence
  • Are synergistic
  • Act at gene promoters and enhancers and facilitate 3D interactions
  • Perpetuate levels of gene activity when cells divide
  • Are influenced by genetics, environment, and developmental noise
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86
Q

What are the four Rs of epigenetic change?

A

Recruiters

wRiters

Readers

eRasers

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87
Q

What happens in the ‘Recruiters’ phase of epigenetics change?

A

Sequence-specific factors (recruiters) bind to DNA

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88
Q

What are some examples of sequence-specific factors (recruiters)?

A

Transcription factors

Non-coding RNAs

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89
Q

What happens in the ‘wRiters’ phase of genetic change?

A

Epigenetic modifers (writers) recruited

Add epigenetic marks to DNA (ie. methyl, aceyl etc)

90
Q

What happens in the ‘Readers’ phase of epigenetic change’?

A

Epigenetic marks bound (“read”) by complexes of proteins

91
Q

What is an example of epigenetic modifiers?

A

Methyl/acetyl … transferase

92
Q

Which proteins “read” epigenetic marks on the DNA?

A

Chromodomain proteins

93
Q

Which protein erases epigenetic marks?

A

Histone deacetylases (HDACs)

94
Q

List the factors that influence epigenetics in order of influence

A
  1. Developmental noise
  2. Genetics
  3. Environment
95
Q

What are the different levels that can be effected by epigenetics?

A

Single genes all the way up to entire genomes

96
Q

What is an example of whole chromosomes being affected by epigenetics?

A

X inactivation

97
Q

How many generations do female epigenetics tend to last? What about males?

A

Females: 3

Males: 2

98
Q

Define

Antenatal

A

before birth; during or relating to pregnancy.

99
Q

Define

Cerebral palsy (CP)

A

a neurological condition caused by brain damage and it is the most common motor and movement disability of childhood. It causes a range of disabilities, from mild to severe

100
Q

Define

Glucocorticoid

A

a class of corticosteroids, which are a class of steroid hormones. They are part of the feedback mechanism in the immune system, which reduces certain aspects of immune function, such as inflammation

101
Q

Define

Preterm

A

born or occurring after a pregnancy significantly shorter than normal, especially after no more than 37 weeks of pregnancy.

102
Q

Define

Twin-twin transfusion syndrome

A

a rare, serious condition that can occur in pregnancies when identical twins share a placenta. Abnormal blood vessel connections form in the placenta and allow blood to flow unevenly between the babies.

103
Q

Define

Periventricular leukomalacia

A

a type of brain injury that affects premature infants. The condition involves the death of small areas of brain tissue around fluid-filled areas called ventricles. The damage creates “holes” in the brain.

104
Q

Define

Tocolytic therapy

A

drugs that are used to delay delivery for a short time (up to 48 hours)

105
Q

Define

Interuterine/fetal growth restriction (IUGR/FGR)

A

a condition in which a baby’s growth slows or stops during pregnancy

106
Q

Define

Brain sparing

A

characterised by preferential flow of blood towards the brain at the expense of the other vital organs, and it occurs as a haemodynamic adaptation in foetuses which have placental insufficiency

107
Q

Define

Sildenafil citrate (Viagra)

A

a medication used to treat erectile dysfunction and pulmonary arterial hypertension

108
Q

Define

Perinatal asphyxia

A

a severe and prolonged lack of oxygen immediately before or during birth; causes include inadequate uterine relaxation, cord compression, placental abruption, etc.

109
Q

Define

Hypoxic ischemic encephalopathy (HIE)

A

the brain injury caused by oxygen deprivation to the brain, also commonly known as intrapartum asphyxia. The newborn’s body can compensate for brief periods of depleted oxygen, but if the asphyxia lasts too long, brain tissue is destroyed

110
Q

Define

Hypothermia

A

involves placing the newborn on a waterproof blanket that contains cool circulating water. The treatment reduces the infant’s temperature as low as 91.4 °F and maintains it there for 72 hours. Caregivers then allow the infant’s body temperature to return to normal

111
Q

Define

Fetal biometry

A

a measurement of the fetus taken during a standard ultrasound

112
Q

Define

Postnatal

A

relating to or denoting the period after childbirth.

113
Q

Define

Fetoscopy

A

an endoscopic procedure during pregnancy to allow surgical access to the fetus, the amniotic cavity, the umbilical cord, and the fetal side of the placenta. A small (3–4 mm) incision is made in the abdomen, and an endoscope is inserted through the abdominal wall and uterus into the amniotic cavity.

114
Q

Define

Monochorionic

A

identical twins who share one placenta

115
Q

Definition

before birth; during or relating to pregnancy.

A

Antenatal

116
Q

Definition

a neurological condition caused by brain damage and it is the most common motor and movement disability of childhood. It causes a range of disabilities, from mild to severe

A

Cerebral palsy (CP)

117
Q

Definition

a class of corticosteroids, which are a class of steroid hormones. They are part of the feedback mechanism in the immune system, which reduces certain aspects of immune function, such as inflammation

A

Glucocorticoid

118
Q

Definition

born or occurring after a pregnancy significantly shorter than normal, especially after no more than 37 weeks of pregnancy.

A

Preterm

119
Q

Definition

a rare, serious condition that can occur in pregnancies when identical twins share a placenta. Abnormal blood vessel connections form in the placenta and allow blood to flow unevenly between the babies.

A

Twin-twin transfusion syndrome

120
Q

Definition

a type of brain injury that affects premature infants. The condition involves the death of small areas of brain tissue around fluid-filled areas called ventricles. The damage creates “holes” in the brain.

A

Periventricular leukomalacia

121
Q

Definition

drugs that are used to delay delivery for a short time (up to 48 hours)

A

Tocolytic therapy

122
Q

Definition

a condition in which a baby’s growth slows or stops during pregnancy

A

Interuterine/fetal growth restriction (IUGR/FGR)

123
Q

Definition

characterised by preferential flow of blood towards the brain at the expense of the other vital organs, and it occurs as a haemodynamic adaptation in foetuses which have placental insufficiency

A

Brain sparing

124
Q

Definition

a medication used to treat erectile dysfunction and pulmonary arterial hypertension

A

Sildenafil citrate (Viagra)

125
Q

Definition

a severe and prolonged lack of oxygen immediately before or during birth; causes include inadequate uterine relaxation, cord compression, placental abruption, etc.

A

Perinatal asphyxia

126
Q

Definition

the brain injury caused by oxygen deprivation to the brain, also commonly known as intrapartum asphyxia. The newborn’s body can compensate for brief periods of depleted oxygen, but if the asphyxia lasts too long, brain tissue is destroyed

A

Hypoxic ischemic encephalopathy (HIE)

127
Q

Definition

involves placing the newborn on a waterproof blanket that contains cool circulating water. The treatment reduces the infant’s temperature as low as 91.4 °F and maintains it there for 72 hours. Caregivers then allow the infant’s body temperature to return to normal

A

Hypothermia

128
Q

Definition

a measurement of the fetus taken during a standard ultrasound

A

Fetal biometry

129
Q

Definition

relating to or denoting the period after childbirth.

A

Postnatal

130
Q

Definition

an endoscopic procedure during pregnancy to allow surgical access to the fetus, the amniotic cavity, the umbilical cord, and the fetal side of the placenta. A small (3–4 mm) incision is made in the abdomen, and an endoscope is inserted through the abdominal wall and uterus into the amniotic cavity.

A

Fetoscopy

131
Q

Definition

identical twins who share one placenta

A

Monochorionic

132
Q

What percentage of cerebral palsy is caused by damage to the brain that occurred during pregnancy or at birth?

A

95%

133
Q

Approximately what percentage of babies were born preterm in Australia last year?

A

8.6%

134
Q

Antenatal glucocorticoid therapy has what outcomes on preterm labour?

A

decrease perinatal mortality by 50%

decrease the incidence of respiratory distress syndrome by 40%

Glucocorticoids also have a range of nonpulmonary effects, particularly on the fetal cardiovascular system and the brain.

135
Q

Which condition are most commonly treated by fetal surgery?

A

Twin-twin transfusion syndrome

Spina bifida

Congenital diaphragmatic hernia

Congenital lung malformation

Congenital heart defects

136
Q

How common is twin-twin transfusion syndrome in MZ twins?

A

Occurs in 10-15%

137
Q

What causes cerebral palsy?

A

Occurs as a result of a lesion within the brain during brain development

138
Q

True or False:

Cerebral palsy gets progressively worse as individuals age

A

False

It is non-progressive

139
Q

What type of brain matter is typically affected in cerebral palsy?

A

White matter

140
Q

What four compromsised situations lead to incorrect brain development and injury?

A
  1. intrauterine growth restriction (IUGR)
  2. intrauterine infection
  3. birth asphyxia
  4. preterm birth
141
Q

Other than preterm, what are the other risk-factors for cerebral palsy?

A

Interuterine growth restriction (IUGR)

Infection

142
Q

How can infection lead to cerebral palsy?

A

Produce a strong fetoplacental inflammatory response leads to upregulation of pro-inflammatory cytokines which can access the fetal brain

143
Q

What is the single greatest cause of perinatal death, or morbidity in survivors?

A

Preterm birth

144
Q

What therapy options can ensure the fetus remains in utero for longer?

A

Tocolytic therapy

  • Prostoglandin inhibitors
  • Magnesium sulfate
  • Calcium channel blockers
145
Q

What are the 3 types of tocolytic therapy?

A

Prostoglandin inhibitors

Magnesium sulfate

Calcium channel blockers

146
Q

What is the relationship between tocolytics and neonatal outcome?

A

On their own, tocolytics do not imporve neonatal outcome. But, the are often effective at delaying labour for 48 hours

147
Q

What intrinisic protective mechanism is used during intrauterine growth restiction (IUGR)?

A

Brain sparing

148
Q

What happened to lamb fetuses when they were given sidenafil citrate (viagra) for IUGR?

A
  • induced hypoxia, and worsened hypoxia in IUGR
  • caused a pronounced cardiovascular response
149
Q

What is the difference between the blood oxygen levels, carotid blood flow and peripheral blood flow in healthy individuals, IUGR individuals and IUGR treated with viagra?

A

Health (control)

Blood-oxygen levels: normal

Carotid blood flow: normal

Peripheral blood flow: normal

IUGR

Blood-oxygen levels: slightly lower than control

Carotid blood flow: normalish

Peripheral blood flow: decreased

IGUR + viagra

Blood-oxygen levels: lower than both IUGR and control

Carotid blood flow: normalish

Peripheral blood flow: gradually increasing

150
Q

Normal levels of carotid (brain) blood flow and decreased peripheral blood flow indicates what phenomenon in IUGR babies?

A

Brain sparing

151
Q

What was unable to occur in IUGR babies given viagra?

A

Brain sparing: all vessels dialated increased the blood flow back to the periphery. No protective mechanism

152
Q

What happens to the white matter and oxdative stress in IUGR babies?

A

Decreased white matter tracts and increased oxidative stress

153
Q

What happens to IUGR babies given melatonin? Why?

A

Increases their white matter tracts and decreases oxidative stress. Melatonin is an antioxidant, which improved overall cellular development and brain function in IUGR?

154
Q

In what ways has melatonin been found to effect IUGR in humans?

A
  1. Improved placental blood flow
  2. Decreased oxidative stress
  3. Does not prolong pregnancy
  4. Reduced the incidence of brain harmorrhage (maybe)
  5. Improved cardiovascular outcomes
155
Q

What non-pulmonary effects can glucocorticoids have on IUGR babies?

A

hypertension

increased vascular resistance

mild hypoxaemia

growth restriction

decreased brain weight

altered brain development

156
Q

What is the resultant brain injury of perinatal asphyxia called?

A

Hypoxic Ischemic Encephalopathy (HIE)

157
Q

________________ begun soon after birth significantly reduces death and disability in infants with hypoxic ischemic encephalopathy (HIE), caused by birth asphyxia

A

HYPOTHERMIA begun soon after birth significantly reduces death and disability in infants with hypoxic ischemic encephalopathy (HIE), caused by birth asphyxia

158
Q

How effective is hypothermia at treating hypoxic ischemic encephalopathy (HIE)?

A

Successful in 1/9 cases

159
Q

In what ways can we “access” the fetus to improve long-term health outcomes?

A

Ultrasounds

MRI

Fetoscopy

Maternal circulation

Trans-placental

160
Q

What information can fetal ultrasound give us?

A

Fetal biometry (measurements)

Pregnancy location

Accurate dating

Chorionicity

Fetal anatomy

161
Q

What are some examples of ultrasound guided procedures in fetuses?

A

Chorionic villi sampling

Amniocentesis

162
Q

What is the main issue of usign MRI for imaging fetuses?

A

They move so much!

163
Q

In what way is MRI better than ultrasound for imaging fetuses?

A

They provide a much better resolution of the babies brain. MRI will detect CNS abnormalities in 50% of fetuses with mild VM not seen on ultrasound

164
Q

Which “accessing” techniques is used in twin-twin transfusion syndrome treatment?

A

Fetoscopy

165
Q

Why does treating conditions in utero by surgically opening the uterus pose such a risk?

A

The wounds in the uterus and abdomin are at a high risk of opening up, particularly during labour, leading to bleeding

166
Q

What information can the maternal ciruclation provide about the baby?

A

The placental releases genetic information into the maternal circulation providing genetic information and biomarkers that can be access non-invasively

167
Q

What is the limiting feature of using maternal blood to assess the fetus?

A

There is a very small proportion of genetic information in the blood that belongs to the baby, particularly early on

168
Q

Which conditions already have maternally administered drugs that can be used for fetal therapy?

A

Fetal tachyarrhythmias

Fetal lung and brain maturity

Cogenital adrenal hyperplasia

Hypothyroidism

169
Q

Which drugs are currently being investigated for potential fetal protection?

A

Melatonin

Creatine

170
Q

Why in In utero stem cell transplantation typically unsuccessful?

A

Fetuses have a better immune system that we initially expected. Stems cells were cleared

171
Q

Define

Aneuploidy

A

the presence of an abnormal number of chromosomes in a cell, for example a human cell having 45 or 47 chromosomes instead of the usual 46

172
Q

Define

Primordial follicles

A

consist of an oocyte surrounded by a single layer of flattened granulosa cells. They can grow into primary follicles, which contain an oocyte surrounded by a layer of cuboidal granulosa cells

173
Q

Define

Oocyte

A

a cell in an ovary which may undergo meiotic division to form an ovum.

174
Q

Define

Assited reproductive technologies (ART)

A

technologies and associated methods used to assist people in achieving a pregnancy

175
Q

Define

Intracytoplasmic sperm injection (ICSI)

A

performed as an additional part of an IVF treatment cycle where a single sperm is injected into each egg to assist fertilisation using very fine micro-manipulation equipment

176
Q

Define

IVF

A

a process of fertilisation where an egg is combined with sperm outside the body, in vitro

177
Q

Define

Menopause

A

occurs when a woman hasn’t menstruated in 12 consecutive months and can no longer become pregnant naturally

178
Q

Define

Fecundity

A

the ability to produce an abundance of offspring or new growth

179
Q

Define

Polar body

A

a small haploid cell that is formed concomitantly as an egg cell during oogenesis, but generally does not have the ability to be fertilized

180
Q

Define

Non-disjunction

A

chromosomes failing to separate correctly, resulting in gametes with one extra, or one missing, chromosome (aneuploidy)

181
Q

Define

Cohesin

A

a protein complex that mediates sister chromatid cohesion, homologous recombination and DNA looping

182
Q

Define

Separase

A

a cysteine protease responsible for triggering anaphase by hydrolysing cohesin, which is the protein responsible for binding sister chromatids during the early stage of anaphase

183
Q

Definition

the presence of an abnormal number of chromosomes in a cell, for example a human cell having 45 or 47 chromosomes instead of the usual 46

A

Aneuploidy

184
Q

Definition

consist of an oocyte surrounded by a single layer of flattened granulosa cells. They can grow into primary follicles, which contain an oocyte surrounded by a layer of cuboidal granulosa cells

A

Primordial follicles

185
Q

Definition

a cell in an ovary which may undergo meiotic division to form an ovum.

A

Oocyte

186
Q

Definition

technologies and associated methods used to assist people in achieving a pregnancy

A

Assited reproductive technologies (ART)

187
Q

Definition

performed as an additional part of an IVF treatment cycle where a single sperm is injected into each egg to assist fertilisation using very fine micro-manipulation equipment

A

Intracytoplasmic sperm injection (ICSI)

188
Q

Definition

a process of fertilisation where an egg is combined with sperm outside the body, in vitro

A

IVF

189
Q

Definition

occurs when a woman hasn’t menstruated in 12 consecutive months and can no longer become pregnant naturally

A

Menopause

190
Q

Definition

the ability to produce an abundance of offspring or new growth

A

Fecundity

191
Q

Definition

a small haploid cell that is formed concomitantly as an egg cell during oogenesis, but generally does not have the ability to be fertilized

A

Polar body

192
Q

Definition

chromosomes failing to separate correctly, resulting in gametes with one extra, or one missing, chromosome (aneuploidy)

A

Non-disjunction

193
Q

Definition

a protein complex that mediates sister chromatid cohesion, homologous recombination and DNA looping

A

Cohesin

194
Q

Definition

a cysteine protease responsible for triggering anaphase by hydrolysing cohesin, which is the protein responsible for binding sister chromatids during the early stage of anaphase

A

Separase

195
Q

Which phase of the cell cycle do primordial follicles arrest in?

A

They arrest in meiotic prophase; equivalent to mitotic G2 phase

196
Q

Which hormone is responsible for a decrease in female fertility in a normal reproductive cycle?

A

Progesterone

197
Q

Which two hormones spike rapidly at ovulation?

A

LH and FSH

198
Q

How can infertility be treated?

A

Assisted reproductive technologies (i.e. IVF and ICSI)

199
Q

True or False:

Human oocytes are very resilient and rarely burst during ICSI

A

True

200
Q

How successful is IVF/ART in general? What about for people less than 30 or people 40-44?

A

Its complicated: patient selection, diagnosis, how success is measured

For <30 40% chance of live birth

For 40-44 10% chance of live birth

201
Q

What is the average age of menopause?

A

50

202
Q

At what age does fertility begin to rapidly decline?

A

36-40

203
Q

When are primoridal follicles formed?

A

During foetal life

204
Q

How do we know that its the oocyte quality decreasing with age and not some other area of the female reproductive system?

A

Live births with donor eggs stay reletively consistent (up until late 40s) where as live births with own eggs starts to decrease gradually after ~30

205
Q

What is the link between chromosomal abnormalities and spontaneous abortions?

A

Both start to rapidly increase after a maternal age of ~35

206
Q

When do oocytes finish their second meiotic division?

A

When they are fertilised by the sperm

*they are never truly haploid*

207
Q

Chromosomes are separated on a _______ that is very dynamic and very sensitive

A

Chromosomes are separated on a microtubule spindle that is very dynamic and very sensitive

208
Q

What happens to chromosome seperation by spindles in oocytes as females age?

A

Increased likelyhood of non-disjunction during meiosis; increases aneuploidy chance

209
Q

What is more catestrophic: nondisjuction during meiosis I or II?

A

Meiosis I

Oocyte guaranteed to be aneuploidy compared to a 50% chance if nondisjunction occurs in meiosis II

210
Q

How do chromosomal errors arise in meiosis metaphase ?

A

Incorrect attachment of spindles

Premature separation

Bivalent rotaion

211
Q

What causes lagging chromosomes?

A

Chromosome attached to both poles of the cell

212
Q

_________ holds chromosomes together and is decreased in old eggs

A

Cohesion holds chromosomes together and is decreased in old eggs

213
Q

How does loss of cohesion cause segregation errors?

A

Cohesin prevents premature and random segregation of chromatids

214
Q

We inherit all our mitochondrial DNA from where?

A

Maternal oocyte

215
Q

What are the two main features of oocyte mitochondria?

A
  1. Mitochondria are highly mobile and dynamic
  2. Mitochondria in oocytes are highly active and responsive
216
Q

ATP from where helps maintain the meiotic spindle?

A

Mitochondria

217
Q

What happens to the meiotic spindle when there is no ATP?

A

The spindle disappers

218
Q

What happens to Ca2+ and ATP levels after fertilisation?

A
219
Q

Which molecules in oocytes causes an increase in mitochondrial activity?

A

Ca2+

220
Q

Which product of the electron transport chain can damage the cell?

A

Reactive oxidative species (ROS)

Increases with age

STUFF (6 decks)

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