Midterm 1 Flashcards
Describe the epidemiological and experimental evidence that links early life environments to pregnancy outcomes, adverse development and disease
- Malnutrition: Too much or too little nutrient intake is tied to chronic disease risk.
(Nutrition is one of many environmental influences) - Obesity: increased exposure to energy dense, nutrient poor foods, and lack of physical activity
- low birth weight is a surrogate
Define developmental plasticity
Ability of an organism to develop in various ways,
depending on the particular environment or setting
* Multiple phenotypes can arise during development from a
single genotype
* Different phenotypes are based on the nature of the gene –
environment interactions (GXE)
* Normal aspect of development
Identify critical windows of plasticity across the lifespan
Define Evolutionary and Developmental
Mismatch: between the environment in uterine vs adult
Evolutionary Mismatch = environments experienced by
contemporary humans are markedly different from those
encountered throughout most of our evolutionary history
* Changes in our nutritional environment appetite-rewarding energy-
dense foods;
* Replacement of human breast milk with bottle feeding using cow’s milk-
based formula
* In vitro fertilization
Developmental Mismatch = later life environment is different
from that predicted in early life maladaptation
* Maternal illness
* Placental disease
* Unbalanced maternal diet
* Significant change in the post-natal environment
Can provide false in utero cues
Describe and identify common surrogates of the intrauterine environment
low birth weight???
both animal and human research is now that phenotypes can be induced in offspring without necessarily being accompanied by …
low birthweight, it is clear that reduction of fetal growth per se does not lie on a causal pathway to later disease.
Rather, low birthweight is a surrogate marker of the effects of the prenatal environment on the fetus, and one aspect of the fetal ‘coping’ responses to that environment
‘Barker hypothesis’
“exposure to environmental factors during specific sensitive periods of development might predispose an organism to diseases in adult life.”
Chronic disease is more than just ____ and _____ adult lifestyles.
- bad genes
- unhealthy
Ischaemic heart disease is strongly correlated with both neonatal and postneonatal mortality. It is suggested that poor nutrition in ____ increases susceptibility to the effects of an affluent diet
early life
neonatal vs post-neonatal
___ birth weight was also found to be associated with disorders characterized by insulin resistance, such as type 2 diabetes (T2D), hypertension, and dyslipidemia (abnormaly high levels of lipids in the blood).
LOW
Hertfordshire Cohort Study
The Hertfordshire Cohort Study is a nationally unique study of men and women born in the English county of Hertfordshire in the early part of the 20thcentury. Records that detail their health in infancy and childhood have been preserved, their sociodemographic, lifestyle, medical and biological attributes have been characterised in later life, and routinely collected data on their hospital use and mortality have been acquired.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6381804/
intrauterine
within the uterus
Helsinki Birth Cohort (1924-1933; 1934-1944)
There is now clear evidence that the pace and pathway of early growth is a major risk factor for the development of a group of chronic diseases that include coronary heart disease, stroke, type 2 diabetes and hypertension. This has led to a new ‘developmental’ model for these disorders. The so-called ‘fetal origins hypothesis’ proposes that the disorders originate through developmental plasticity, whereby malnutrition during fetal life, infancy and early childhood permanently change the structure and function of the body, a phenomenon known as ‘programming’. This paper reviews recent findings in the Helsinki Birth Cohort, which comprises 13 345 men and women born in the city during 1934-1944. There is also an older cohort comprising 7086 people born during 1924-1933. We review the paths of pre- and postnatal growth that lead to later disease. Children who later develop coronary heart disease and type 2 diabetes grow slowly during fetal life and infancy but thereafter increase their body mass indices rapidly. Those who later develop stroke grow slowly in fetal life, infancy and during childhood. We also review how the growth of girls during infancy, childhood and at puberty influences chronic disease in the next generation.
Standardized Mortality Ratio(SMR)
is aratiobetween the observed number of deaths in an study population and the number of deaths would be expected, based on the age- and sex-specific rates in astandardpopulation and the population size of the study population by the same age/sex groups.
Dutch Hunger Winter (1944-1945)
intrauterine environment.
A baby grows inside the mother’s womb or uterus.
Barkers Hypothesis
Inadequate nutrition
in utero poor fetal growth/low birthweight metabolic and cardiovascular disease in later life
Fetal Origins of Adult Disease (FOAD)
Intrauterine environmental (not just nutrition) exposures affect thefetus’ development during sensitive periods increases the risk of specificdiseasesinadultlife
(CVD and type 2 diabetes)
3 characteristics of Developmental Plasticity:
- the nature of the response will in part be dependent on the nature of
the environmental cue. - there are critical windows for plasticity in different systems – when
system is most vulnerable to change. - the duration of developmental plasticity is time-limited: once
organogenesis is complete (structure & function), plasticity is no
longer possible (limited).
Define Developmental PROGRAMMING
Developmental programming = process whereby a stimulus or insult,
applied at a ‘‘sensitive’’ or ‘‘critical’’ period of development, has
lasting effects on the structure or function of the body.
* Operates within the context of plasticity
* leading to enhanced susceptibility to later disease
Define Developmental PLASTICITY
- Developmental plasticity = the ability of a single genotype to
produce more than one alternative form of structure, physiological
state or behaviour in response to environmental conditions - Aspect of normal development
- Refers to the potential to be altered
Thrifty Phenotype Hypothesis
The thrifty phenotype hypothesis theorizes that instead of arising genetically, the “thrifty factors” developed as a direct result of the environment within the womb during development.
Define Multiple hits:
- Adversity in early development
places offspring at risk for
disease in adulthood (first hit) - Pathogenesis of disease is also
determined by postnatal
challenges second(+) hit - Reveals underlying vulnerability
set up by early life exposures - Stressors, nutrition, disease,
infection, toxicant exposure
___ billion overweight ____ million obese
1.9 billion: 600 million
the placenta
vital organ of pregnancy required for fetal survival and growth
- formed from both maternal and embryonic tissue
- functions as lungs, liver, gut, kidneys, endocrine glands, and defensive barrier
- provides oxygen and nutrients to the developing fetus
- removes waste products
- protects the fetus from endogenous factors including: infectious substances and maternal immune cells, maternal hormones, xenobiotics
what are the dimensions of the placenta at term:
- diameter: 15-25 cm
- thickness: 2.5-3 cm
-weight: 450-600g
what is the fetal surface
chronic plate covered by amniotic membrane. Number of chorionic vessels converging toward the umbilical cord
Placenta -> interface between fetus and
mother
environmental exposures can alter placental structure and function
- changes in the supply of nutrients, oxygen and methyl donors
- alterations in hormones and other signaling molecules
The placenta responds by transmitting programming stimuli to
to the fetus
Mechanisms that regulate placental growth and development also serves as causative agents for
programming of chronic disease.
Placental size and mass are crude measures
of function
Efficiency = placental weight (PW): fetal weight (FW)
How much fetal mass has accumulated for every gram of placenta
Typically applied at term
Does not offer insight into the regulation of placental or fetal growth
crude marker of environmental conditions (i.e. nutrition, microbiome)
Placenta measurements recorded at the population level and associated with long term health outcomes
All Helsinki hospitals, The Netherlands, India and Saudi Arabia.
The placenta can alter its growth trajectory according to the
availability of nutrients
Important take home messages about the placenta
- Adequate fetal growth and development depends on an adequate placenta
- The placenta, like other organs, has critical windows of plasticity
- Failure to mount a robust response to external insults can lead to placental insufficiency and fetal compromise
Environmental exposures may disrupt placental nutrient, drug and other transport mechanisms
Increasing fetal exposure to maternally derived metabolites, toxins, xenobiotics, hormones
A reduced defensive barrier may also enable inflammatory mediators to enter the fetal compartment
These may be particularly detrimental to the developing brain
The placenta’s capacity for nutrient transport can be altered by changes in transporter:
Number
Density
Distribution
Activity
Dysregulation of transport systems will impact fetal growth/development
Resulting altered body composition and function may have long-term implications.
Fetal Growth Restriction -
fetus not reaching its predetermined growth potential
Placental Dysfunction
Insufficient remodeling of the spiral arteries reduction in nutrient and oxygen delivery
Maternal Undernutrition
Inadequate food supply or deliberate calorie restriction
reduction in nutrient and oxygen delivery
Nutrient supply to the fetus is insufficient despite adequate nutrient availability in the mother
Inadequate food supply or deliberate calorie restriction
Insufficient availability of nutrients in maternal circulation
Nutrient transporters: Glucose
Fetal hypoglycemia is implicated in fetal growth restriction
No reduction in placental glucose uptake or expression of GLUT1
⬆️ expression of GLUT3 protein in late-term FGR cytotrophoblast increased consumption of glucose by placenta
Amino Acids
Reduced expression and activity of amino acid transporters
⬇️ System A activity in MVM (unaltered in BM)
⬇️ System L activity in MVM and BM
Reduced AA concentration in umbilical cord blood
