Developmental Origins of Health and Disease Flashcards
Define
Non-communicable disease (NCD)
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.
Define
Developmental Origins of Health and Disease (DOHaD) Hypothesis
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
Define
Metanephroi
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.
Define
Nephrogenesis
describes the embryologic origins of the kidney, a major organ in the urinary system
Define
Brenner Hypothesis
states that individuals with a congenital reduction in nephron number have a much greater likelihood of developing adult hypertension and subsequent renal failure
Define
Barker Hypothesis
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
Define
Nephrons
a filtering unit in kidneys that are made up of glomeruli and tubules
Define
Glomeruli
a network of small blood vessels (capillaries) known as a tuft, located at the beginning of a nephron in the kidney
Define
Pronephroi
the first in a sequence of kidneys that form in vertebrate embryos
Define
Mesonephroi
the excretory organ of the embryo, arising caudad to the pronephros and using its duct.
Define
Ureteric bud
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
Define
Metanephric mesenchyme (MM)
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.
Define
Pertuburations
an alteration of the function of a biological system by external or internal means such as environmental stimuli, drug inhibition, and gene knockdown
Define
Hypertension
high blood pressure
Define
Chronic Kidney Disease (CKD)
a condition characterized by a gradual loss of kidney function over time
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.
Non-communicable disease (NCD)
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
Developmental Origins of Health and Disease (DOHaD) Hypothesis
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.
Metanephroi
Definition
describes the embryologic origins of the kidney, a major organ in the urinary system
Nephrogenesis
Definition
states that individuals with a congenital reduction in nephron number have a much greater likelihood of developing adult hypertension and subsequent renal failure
Brenner Hypothesis
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
Barker Hypothesis
Definition
a filtering unit in kidneys that are made up of glomeruli and tubules
Nephrons
Definition
a network of small blood vessels (capillaries) known as a tuft, located at the beginning of a nephron in the kidney
Glomeruli
Definition
the first in a sequence of kidneys that form in vertebrate embryos
Pronephroi
Definition
the excretory organ of the embryo, arising caudad to the pronephros and using its duct.
Mesonephroi
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
Ureteric bud
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.
Metanephric mesenchyme (MM)
Definition
an alteration of the function of a biological system by external or internal means such as environmental stimuli, drug inhibition, and gene knockdown
Pertuburations
Definition
high blood pressure
Hypertension
Definition
a condition characterized by a gradual loss of kidney function over time
Chronic Kidney Disease (CKD)
What diseases are considered to be non-communicable?
Cardiovascular disease
Cancer
Chronic respiratory diseases
Chronic kidney disease
Diabetes
What are some examples of modifiable behavioural risk factors of chronic disease?
Tobacco
Physical inactivity
Unhealthy diet
Alcohol
What are some examples of metabolic/physiological risk factors of chronic disease?
Raised blood pressure
Overweight/obesity
Hyperglycaemia (high blood glucose levels)
Hyperlipidaemia (high levels of fats in the blood)
Do poor living conditions in childhood and adolescence increase risk for arteriosclerotic heart disease?
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
True or False:
Birth weight has considerable predictive ability for increased risk of disease in adult life
True
During the Dutch Hunger Winter, individual exposed to famine in early gestation had what? What about those exposed in late gestation?
Early gestation had
- atherogenic plasma lipid profile
- central obesity
- increased risk of coronary heart disease
Late gestation had
- impaired glucose tolerance
True or False:
Males are more sensitive to DOHaD than females
True
What are the three pairs of excretory organs developed by mammals?
- Pronephroi
- Mesonephroi
- Metanephroi
Which of the three pairs of excretory organs developed by mammals is the permanent kidney?
Metanephroi
How does the metanephroi develop?
- 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
Signals from __________ induce branching morphogenesis. Signals from the branch (ureteric epithelial) tips induce __________.
Signals from metanephric mesenchyme (MM) induce branching morphogenesis. Signals from the branch (ureteric epithelial) tips induce nephrogenesis.
What does the ureteric bud give rise to?
Collecting ducts
Calyces
Pelvis
Ureter
What does the metanephric mesenchyme give rise to?
- Nephron
- Glomerulus (capillaries)
- Proximal convoluted tubule
- Loop of Henle
- Distal convoluted tubule
- Interstitium
What is renal hypoplasia/dysplasia?
Small/abnormal kidney
What is Renal Agenesis (unilateral/bilateral)?
Absent kidney
What is a Multicystic kidney?
Presence of multiple cysts in the kidney
What is a duplex kidney?
One ureter with a duplicated collecting system due to bifurcation of the ureter or 2 ureters.
What is a Vesicoureteric reflux (VUR)?
Backward flow of urine into the kidney
What is a Hydroureter?
Dilated ureter
What is Hydronephrosis?
Dilation of the renal pelvis
What is a Obstruction at vesicoureteric (VUJ) junction?
Obstruction at ureter-bladder junction
What is a Obstruction at ureteropelvic (UPJ) junction?
Obstruction at ureter-renal pelvis junction
What causes CAKUT?
- 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
Outline the steps in the Brenner Hypothesis cycle?
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
Animal models fo kidney development have shown that which factors contribute to low nephron number?
Calorie restriction
Protein restriction
Vitamin deficiency
Excess glucocorticoid
Placental insufficiency
Hypoxia
Antibiotic exposure
Maternal anaemia
How is the Barker and Brenner hypotheses linked?
Define
Epigenetics
the molecular mechanisms that control gene activity that enable development to occur
Define
Transgenerational epigenetic inheritance
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
Define
Chromatin remodellers
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
Define
Long ncRNA
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)
Define
Transferase
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).
Define
Chromodomain
a protein structural domain of about 40–50 amino acid residues commonly found in proteins associated with the remodeling and manipulation of chromatin
Define
Histone deacetylases (HDACs)
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
Define
Imprinting
an epigenetic phenomenon that causes genes to be expressed in a parent-of-origin-specific manner
Define
X inactivation
a process by which one of the copies of the X chromosome is inactivated in therian female mammals
Definition
the molecular mechanisms that control gene activity that enable development to occur
Epigenetics
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
Transgenerational epigenetic inheritance
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
Chromatin remodellers
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)
Long ncRNA
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).
Transferase
Definition
a protein structural domain of about 40–50 amino acid residues commonly found in proteins associated with the remodeling and manipulation of chromatin
Chromodomain
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
Histone deacetylases (HDACs)
Definition
an epigenetic phenomenon that causes genes to be expressed in a parent-of-origin-specific manner
Imprinting
Definition
a process by which one of the copies of the X chromosome is inactivated in therian female mammals
X inactivation
When does nephrogenesis end in humans?
Shortly before term birth
How many nephrons does the normal human kidney contain?
Textbooks state 1 million nephrons
In reality it is an incredibly wide range
True or False:
Indigenous Australians have a similar number of nephrons to White Australians
False
They have considerably less
How is birth weight related to nephron number?
As BW increases so does nephron number
What can we do now to minimise risk of hypertension and kidney disease in individuals?
- 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.
Why is it useful to estimate Glomerular Number and Size In Vivo?
- 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.
What is the most commonly used surrogate index of “developmental success”?
Birth weight
What is LBW associated with?
Low birth weight has been associated with increased risk for a large number of adult chronic diseases, including hypertension and CKD.
What is the specific mechanisms of epigenetics?
DNA (methylation)
RNA (non-coding)
Histones (modified and variant)
Chromatin remodellers
3D nuclear localisation
How to epigenetic mechanisms affects gene regulatory regions?
Epigenetic mechanisms combine to open and close gene regulatory regions
What are the main characteristics of epigenetic mechanisms?
- 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
What are the four Rs of epigenetic change?
Recruiters
wRiters
Readers
eRasers
What happens in the ‘Recruiters’ phase of epigenetics change?
Sequence-specific factors (recruiters) bind to DNA
What are some examples of sequence-specific factors (recruiters)?
Transcription factors
Non-coding RNAs
What happens in the ‘wRiters’ phase of genetic change?
Epigenetic modifers (writers) recruited
Add epigenetic marks to DNA (ie. methyl, aceyl etc)
What happens in the ‘Readers’ phase of epigenetic change’?
Epigenetic marks bound (“read”) by complexes of proteins
What is an example of epigenetic modifiers?
Methyl/acetyl … transferase
Which proteins “read” epigenetic marks on the DNA?
Chromodomain proteins
Which protein erases epigenetic marks?
Histone deacetylases (HDACs)
List the factors that influence epigenetics in order of influence
- Developmental noise
- Genetics
- Environment
What are the different levels that can be effected by epigenetics?
Single genes all the way up to entire genomes
What is an example of whole chromosomes being affected by epigenetics?
X inactivation
How many generations do female epigenetics tend to last? What about males?
Females: 3
Males: 2
Define
Antenatal
before birth; during or relating to pregnancy.
Define
Cerebral palsy (CP)
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
Define
Glucocorticoid
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
Define
Preterm
born or occurring after a pregnancy significantly shorter than normal, especially after no more than 37 weeks of pregnancy.
Define
Twin-twin transfusion syndrome
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.
Define
Periventricular leukomalacia
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.
Define
Tocolytic therapy
drugs that are used to delay delivery for a short time (up to 48 hours)
Define
Interuterine/fetal growth restriction (IUGR/FGR)
a condition in which a baby’s growth slows or stops during pregnancy
Define
Brain sparing
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
Define
Sildenafil citrate (Viagra)
a medication used to treat erectile dysfunction and pulmonary arterial hypertension
Define
Perinatal asphyxia
a severe and prolonged lack of oxygen immediately before or during birth; causes include inadequate uterine relaxation, cord compression, placental abruption, etc.
Define
Hypoxic ischemic encephalopathy (HIE)
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
Define
Hypothermia
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
Define
Fetal biometry
a measurement of the fetus taken during a standard ultrasound
Define
Postnatal
relating to or denoting the period after childbirth.
Define
Fetoscopy
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.
Define
Monochorionic
identical twins who share one placenta
Definition
before birth; during or relating to pregnancy.
Antenatal
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
Cerebral palsy (CP)
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
Glucocorticoid
Definition
born or occurring after a pregnancy significantly shorter than normal, especially after no more than 37 weeks of pregnancy.
Preterm
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.
Twin-twin transfusion syndrome
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.
Periventricular leukomalacia
Definition
drugs that are used to delay delivery for a short time (up to 48 hours)
Tocolytic therapy
Definition
a condition in which a baby’s growth slows or stops during pregnancy
Interuterine/fetal growth restriction (IUGR/FGR)
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
Brain sparing
Definition
a medication used to treat erectile dysfunction and pulmonary arterial hypertension
Sildenafil citrate (Viagra)
Definition
a severe and prolonged lack of oxygen immediately before or during birth; causes include inadequate uterine relaxation, cord compression, placental abruption, etc.
Perinatal asphyxia
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
Hypoxic ischemic encephalopathy (HIE)
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
Hypothermia
Definition
a measurement of the fetus taken during a standard ultrasound
Fetal biometry
Definition
relating to or denoting the period after childbirth.
Postnatal
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.
Fetoscopy
Definition
identical twins who share one placenta
Monochorionic
What percentage of cerebral palsy is caused by damage to the brain that occurred during pregnancy or at birth?
95%
Approximately what percentage of babies were born preterm in Australia last year?
8.6%
Antenatal glucocorticoid therapy has what outcomes on preterm labour?
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.
Which condition are most commonly treated by fetal surgery?
Twin-twin transfusion syndrome
Spina bifida
Congenital diaphragmatic hernia
Congenital lung malformation
Congenital heart defects
How common is twin-twin transfusion syndrome in MZ twins?
Occurs in 10-15%
What causes cerebral palsy?
Occurs as a result of a lesion within the brain during brain development
True or False:
Cerebral palsy gets progressively worse as individuals age
False
It is non-progressive
What type of brain matter is typically affected in cerebral palsy?
White matter
What four compromsised situations lead to incorrect brain development and injury?
- intrauterine growth restriction (IUGR)
- intrauterine infection
- birth asphyxia
- preterm birth
Other than preterm, what are the other risk-factors for cerebral palsy?
Interuterine growth restriction (IUGR)
Infection
How can infection lead to cerebral palsy?
Produce a strong fetoplacental inflammatory response leads to upregulation of pro-inflammatory cytokines which can access the fetal brain
What is the single greatest cause of perinatal death, or morbidity in survivors?
Preterm birth
What therapy options can ensure the fetus remains in utero for longer?
Tocolytic therapy
- Prostoglandin inhibitors
- Magnesium sulfate
- Calcium channel blockers
What are the 3 types of tocolytic therapy?
Prostoglandin inhibitors
Magnesium sulfate
Calcium channel blockers
What is the relationship between tocolytics and neonatal outcome?
On their own, tocolytics do not imporve neonatal outcome. But, the are often effective at delaying labour for 48 hours
What intrinisic protective mechanism is used during intrauterine growth restiction (IUGR)?
Brain sparing
What happened to lamb fetuses when they were given sidenafil citrate (viagra) for IUGR?
- induced hypoxia, and worsened hypoxia in IUGR
- caused a pronounced cardiovascular response
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?
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
Normal levels of carotid (brain) blood flow and decreased peripheral blood flow indicates what phenomenon in IUGR babies?
Brain sparing
What was unable to occur in IUGR babies given viagra?
Brain sparing: all vessels dialated increased the blood flow back to the periphery. No protective mechanism
What happens to the white matter and oxdative stress in IUGR babies?
Decreased white matter tracts and increased oxidative stress
What happens to IUGR babies given melatonin? Why?
Increases their white matter tracts and decreases oxidative stress. Melatonin is an antioxidant, which improved overall cellular development and brain function in IUGR?
In what ways has melatonin been found to effect IUGR in humans?
- Improved placental blood flow
- Decreased oxidative stress
- Does not prolong pregnancy
- Reduced the incidence of brain harmorrhage (maybe)
- Improved cardiovascular outcomes
What non-pulmonary effects can glucocorticoids have on IUGR babies?
hypertension
increased vascular resistance
mild hypoxaemia
growth restriction
decreased brain weight
altered brain development
What is the resultant brain injury of perinatal asphyxia called?
Hypoxic Ischemic Encephalopathy (HIE)
________________ begun soon after birth significantly reduces death and disability in infants with hypoxic ischemic encephalopathy (HIE), caused by birth asphyxia
HYPOTHERMIA begun soon after birth significantly reduces death and disability in infants with hypoxic ischemic encephalopathy (HIE), caused by birth asphyxia
How effective is hypothermia at treating hypoxic ischemic encephalopathy (HIE)?
Successful in 1/9 cases
In what ways can we “access” the fetus to improve long-term health outcomes?
Ultrasounds
MRI
Fetoscopy
Maternal circulation
Trans-placental
What information can fetal ultrasound give us?
Fetal biometry (measurements)
Pregnancy location
Accurate dating
Chorionicity
Fetal anatomy
What are some examples of ultrasound guided procedures in fetuses?
Chorionic villi sampling
Amniocentesis
What is the main issue of usign MRI for imaging fetuses?
They move so much!
In what way is MRI better than ultrasound for imaging fetuses?
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
Which “accessing” techniques is used in twin-twin transfusion syndrome treatment?
Fetoscopy
Why does treating conditions in utero by surgically opening the uterus pose such a risk?
The wounds in the uterus and abdomin are at a high risk of opening up, particularly during labour, leading to bleeding
What information can the maternal ciruclation provide about the baby?
The placental releases genetic information into the maternal circulation providing genetic information and biomarkers that can be access non-invasively
What is the limiting feature of using maternal blood to assess the fetus?
There is a very small proportion of genetic information in the blood that belongs to the baby, particularly early on
Which conditions already have maternally administered drugs that can be used for fetal therapy?
Fetal tachyarrhythmias
Fetal lung and brain maturity
Cogenital adrenal hyperplasia
Hypothyroidism
Which drugs are currently being investigated for potential fetal protection?
Melatonin
Creatine
Why in In utero stem cell transplantation typically unsuccessful?
Fetuses have a better immune system that we initially expected. Stems cells were cleared
Define
Aneuploidy
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
Define
Primordial follicles
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
Define
Oocyte
a cell in an ovary which may undergo meiotic division to form an ovum.
Define
Assited reproductive technologies (ART)
technologies and associated methods used to assist people in achieving a pregnancy
Define
Intracytoplasmic sperm injection (ICSI)
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
Define
IVF
a process of fertilisation where an egg is combined with sperm outside the body, in vitro
Define
Menopause
occurs when a woman hasn’t menstruated in 12 consecutive months and can no longer become pregnant naturally
Define
Fecundity
the ability to produce an abundance of offspring or new growth
Define
Polar body
a small haploid cell that is formed concomitantly as an egg cell during oogenesis, but generally does not have the ability to be fertilized
Define
Non-disjunction
chromosomes failing to separate correctly, resulting in gametes with one extra, or one missing, chromosome (aneuploidy)
Define
Cohesin
a protein complex that mediates sister chromatid cohesion, homologous recombination and DNA looping
Define
Separase
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
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
Aneuploidy
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
Primordial follicles
Definition
a cell in an ovary which may undergo meiotic division to form an ovum.
Oocyte
Definition
technologies and associated methods used to assist people in achieving a pregnancy
Assited reproductive technologies (ART)
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
Intracytoplasmic sperm injection (ICSI)
Definition
a process of fertilisation where an egg is combined with sperm outside the body, in vitro
IVF
Definition
occurs when a woman hasn’t menstruated in 12 consecutive months and can no longer become pregnant naturally
Menopause
Definition
the ability to produce an abundance of offspring or new growth
Fecundity
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
Polar body
Definition
chromosomes failing to separate correctly, resulting in gametes with one extra, or one missing, chromosome (aneuploidy)
Non-disjunction
Definition
a protein complex that mediates sister chromatid cohesion, homologous recombination and DNA looping
Cohesin
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
Separase
Which phase of the cell cycle do primordial follicles arrest in?
They arrest in meiotic prophase; equivalent to mitotic G2 phase
Which hormone is responsible for a decrease in female fertility in a normal reproductive cycle?
Progesterone
Which two hormones spike rapidly at ovulation?
LH and FSH
How can infertility be treated?
Assisted reproductive technologies (i.e. IVF and ICSI)
True or False:
Human oocytes are very resilient and rarely burst during ICSI
True
How successful is IVF/ART in general? What about for people less than 30 or people 40-44?
Its complicated: patient selection, diagnosis, how success is measured
For <30 40% chance of live birth
For 40-44 10% chance of live birth
What is the average age of menopause?
50
At what age does fertility begin to rapidly decline?
36-40
When are primoridal follicles formed?
During foetal life
How do we know that its the oocyte quality decreasing with age and not some other area of the female reproductive system?
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
What is the link between chromosomal abnormalities and spontaneous abortions?
Both start to rapidly increase after a maternal age of ~35
When do oocytes finish their second meiotic division?
When they are fertilised by the sperm
*they are never truly haploid*
Chromosomes are separated on a _______ that is very dynamic and very sensitive
Chromosomes are separated on a microtubule spindle that is very dynamic and very sensitive
What happens to chromosome seperation by spindles in oocytes as females age?
Increased likelyhood of non-disjunction during meiosis; increases aneuploidy chance
What is more catestrophic: nondisjuction during meiosis I or II?
Meiosis I
Oocyte guaranteed to be aneuploidy compared to a 50% chance if nondisjunction occurs in meiosis II
How do chromosomal errors arise in meiosis metaphase ?
Incorrect attachment of spindles
Premature separation
Bivalent rotaion
What causes lagging chromosomes?
Chromosome attached to both poles of the cell
_________ holds chromosomes together and is decreased in old eggs
Cohesion holds chromosomes together and is decreased in old eggs
How does loss of cohesion cause segregation errors?
Cohesin prevents premature and random segregation of chromatids
We inherit all our mitochondrial DNA from where?
Maternal oocyte
What are the two main features of oocyte mitochondria?
- Mitochondria are highly mobile and dynamic
- Mitochondria in oocytes are highly active and responsive
ATP from where helps maintain the meiotic spindle?
Mitochondria
What happens to the meiotic spindle when there is no ATP?
The spindle disappers
What happens to Ca2+ and ATP levels after fertilisation?
Which molecules in oocytes causes an increase in mitochondrial activity?
Ca2+
Which product of the electron transport chain can damage the cell?
Reactive oxidative species (ROS)
Increases with age
