Module 2: Epigenetics & Gestational Diabetes Flashcards
(43 cards)
Birth weights of offspring from mothers affected by the hunger winter
Mother well-fed at conception, malnourished during last trimester = baby small at birth, remained small
Mother malnourished during first trimester only = baby normal at birth, higher rates of obesity, normal and mental health problems
- can carry to grandchildren!
The barker hypothesis
“Developmental origins of adult diseases”
-infant mortality can serve as a marker for poverty
-poverty can affect maternal nutrition and breast milk quality
-areas w higher infant mortality rates also have higher rates of heart disease (approx 50 years later)
Nutritional perturbations during pregnancy- trimester 1
EMBRYONIC GROWTH slowed by undernutrition, over-nutrition cause hyperglycemia (gestational diabetes)
Nutritional perturbations during pregnancy-trimester 2
Undernutrition affects PLACENTAL FUNCTION - alters relationship between fetus, placenta, and mother
Nutritional perturbations during pregnancy - trimester 3
Undernutrition slows FETAL GROWTH to maintain PLACENTAL FUNCTION
-effects on fetus depends on deficiency duration
Undernutrition on fetal and placental hormones
Lowers hormones (insulin, IGF), affects pancreatic development
Relationship between placental weight and birth weight
small placentas (in relation to birthweight) associated with babies who develop diabetes
Hypothesized mechanisms for health of fetus (4 answers)
- Quality and quantity of maternal nutrition
2.Exposure to stress/high levels of glucocorticoids
- Thrifty phenotype hypothesis
4.Genetic/epigenetic influence
1.Quality and quantity of maternal nutrition(under/overnutrition, junk food diet)
Maternal undernutrition = lower birthweight –> increased bl. pr –> impaired glucose homeostasis
Overnutrition (HFD or excess calories) = high circulating glucose
Junk food diet - influences offspring to eat junk food
2.Exposure to stress/high levels of glucocorticoids (cortisol)
Occur w high glucocorticoids (cortisol) or problems in placental barrier
-glucocorticoids regulate fetal organ maturation
-high cortisol = accelerated organ maturation at expense of fetal growth –> born w low body weight
-Placental 11β-HSD2 inactivates cortisol - (lower amount of 1β-HSD2 –> more cortisol –> lowe birthweight)
- The thrifty phenotype hypothesis
Poor nutrition in early life causes permanent changes in genes related to glucose-insulin metabolism
-fetus adapt during nutrient restriction - (reduce insulin secretion, increase bl. glucose levels - more for brain and heart)
-reversible, but becomes permanent if persists
-fetus prepared for undernutrition, given food abundance- problem! (disease)
Epigenetics
Changes in cell function, do not involve DNA sequence
-ex. DNA methylation impacts how genes are expressed, does not alter sequence
4.Genetic/epigenetic influence
-amount of methyl donors in diet influences epigenome
-change in promotor methylation affect gene express. - can extend across generations
-phenotypic affects related to modifications may not be visible until later in life (depend on eviron. factors)
Best studied examples of epigenetic changes in genome
-DNA methylation (CH3 groups added to specific bases)
-Histone modification (acetylation,methylation,etc)
“Histone code”
Collection of all modifications to histones - acetylation, methylation, phosphorylation, ubiquitination
Adding and removing acetyl groups - enzymes
HAT- histone acetylase (adds)
HDAC-histone deacetylase (removes acetyl groups)
Methylation and de-methylation - gene expression
Methylation - turns OFF gene expression –> promotes binding of proteins that silence transcription
De-methylation - turns ON gene expression –> favours transcription
Diet and epigenome
food contains inhibitors and activators of chromatin remodelling enzymes (DNA methyltransferases, histone acetylases, hisone deacetylases)
-can “program” epigenome
Is epigenetic changes inherited through mitosis or meiosis?
Both
Epigenetic “sensitive regions”
-Promotor region
-Metastable epialleles
–>regions of genome that can be epigenetically modified in a variable and reversible manner
Gene promotor example
-Genomic regions at which epigenetic status varies amongst individuals in a population
-DNA methyl & acetyl. of histone tails most studied
3 Types of epialleles
1.Obligatory
-determined by genetic variation, DNA mutation
2.Facilitated
- determined by genetic and environmental factors
3.Pure
- determined by environmental factors
Cis and Trans Obligatory
Cis: epigenetic change occurs at site of mutation
Trans: mutation in one gene causes epigenetic changes elsewhere in genome
