Nutrition in Utero and Throughout Life L8 Flashcards Preview

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Flashcards in Nutrition in Utero and Throughout Life L8 Deck (13):
1

Define epigenetic modification.

Example?

No change to the DNA sequence, but a change to the ‘extra layer’ of genetic regulation.

E.g. DNA methylation, acetylation.

2

Read

Research has shown strong correlation between maternal malnutrition and low birth weight and between over-nutrition and high birth weight.

But what do these effects have on the child and even the grandchildren and beyond?

And can paternal nutrition affect offspring?

Evidence suggests that both maternal and paternal nutrition, or specific aspects of it, have an effect on several generations worth of offspring.

 

Evidence

In human studies, there has been work done on a cohort of individuals who are now growing up (and beginning to have their own children) who were exposed in utero during the Second World War to a period of extreme famine in the Netherlands, referred to as the Dutch Hunger Winter.

Mothers received very inadequate nutrition.

Their offspring are now having/have had children etc. giving us up to 3 generations of valuable data.

The data includes malnutrition at different points of gestation allowing us to see the differing effects of malnutrition at different points of pregnancy.

Examples of data from this:

Men who were in early gestation during the phase of maternal malnutrition- Born with low birth weight but now have an increased rate of obesity. Comparisons were made with same sex siblings who received adequate utero nutrition (controls).

Female babies who were in early gestation during the phase of maternal malnutrition- Born with low birth weight and now exhibit increased insulin resistance. Comparisons were made with same sex siblings who received adequate utero nutrition (controls). Daughters of these women also have lower birthweight comparatively to the general population. No confounding effects were found so there were deemed to be transgenerational effects.

Low birthweight babies have an increased risk of developing metabolic syndrome in later life.

3

We know that epigenetic modification affects the expression of associated genes:

Hypomethylated DNA tends to be actively ____1____.

Generally:

Methylated DNA with deacetylated histones is the repressed ____2____ configuration.

Un-methylated DNA with acetylated histones is the active ____2____ configuration.

1. Transcribed

2. Chromatin

4

At what coding sequence does most methylation occur?

CpG pairs.

5

If the CpG is methylated, it usually means the gene is transcriptionally ______.

Repressed

6

Most C’s (cytosine) in the CpG nucleotide configuration are methylated. Where they are not methylated, they tend to be clustered together in ‘______   ______’.

CpG islands

7

Cytosine is always methylated at the __ carbon position of the organic ring structure.

5

8

What do you call the the enzymes involved in DNA methylation?

DNA methyltransferases

9

Methyl group donated by ____1____ (SAM) which is converted to ____2____ (SAH) during the reaction.

1. S-adenosylmethionine

2. S-adenosylhomocysteine

10

State the reaction pathway of molecules involved in regenerating more SAM from SAH.

Also name the reaction pathway that generates the factor that generates the above regeneration.

SAH → Homocysteine → Methionine → SAM

Folate → Dihydrofolate → Tetrahydrofolate → Methyl-THF

11

Gluconeogenesis is the backward pathway of ______ (ATP production).

Glycolysis

12

Read

We see a difference in DNA methylation and that it gets inherited, but what's the mechanism?

This is a challenge to answer due to what we know about what happens to DNA methylation during the production of gametes and embryogenesis.

Imagine: some DNA methylated on both strands; if DNA methylation was absolutely fixed then you can imagine that it would be inherited. But we know that during gametogenesis and embryogenesis, most DNA methylation is removed (traditionally thought).

So how does the DNA methylation patterns pass through to the child?

Current thinking is that there must be pockets of DNA methylation that are obtained and these are somehow responsible for creating the new DNA methylation pattern copy in the offspring.

So it must physically pass through but the methylation is not absolutely fixed and does change in the production of gametes and the embryo.

Perhaps though, the mechanism is is not generationally passed through but something to do with the uterine environment.

The malnutrition could have caused physiological changes (and therefore difference to the SD mothers) to the uterus causing the foetuses to develop in this constrained environment.

Overall evidence suggests the mechanism is most probably caused by inheritance.

13

What is 'catch-up' growth?

What are its consequences?

If a foetus is born small for gestational age (low birthweight) and has a period of rapid growth to reach a normal growth curve.

Seen to be far worse (in terms of later life health) than if the normal growth trajectory is maintained.