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Pregnancy Timeline by SemestersFetal liver is producing blood cellsHead may position into pelvisBrain convolutions beginFull TermWhite fat begins to be madeWhite fat begins to be madeHead may position into pelvisImmune system beginningImmune system beginningPeriod of rapid brain growthBrain convolutions beginLungs begin to produce surfactantSensory brain waves begin to activateSensory brain waves begin to activateInner Ear Bones HardenBone marrow starts making blood cellsBone marrow starts making blood cellsBrown fat surrounds lymphatic systemFetal sexual organs visibleFinger and toe prints appearFinger and toe prints appearHeartbeat can be detectedHeartbeat can be detectedBasic Brain Structure in PlaceThe Appearance of SomitesFirst Detectable Brain WavesA Four Chambered HeartBeginning Cerebral HemispheresFemale Reproductive SystemEnd of Embryonic PeriodEnd of Embryonic PeriodFirst Thin Layer of Skin AppearsThird TrimesterSecond TrimesterFirst TrimesterFertilizationDevelopmental Timeline
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Home | Pregnancy Timeline | News Alerts |News Archive July 22, 2014

The epigenetic effects of starvation may not last more than two generations.

 






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"You are what your grandfather ate"

A new study raises questions over how epigenetic effects are passed down from one generation to the next — through fathers — and measures how long these effects will have an impact.

When a pregnant mother is undernourished, her child is at a greater than average risk for developing obesity and type 2 diabetes. This is in part due to 'epigenetic' effects — or those effects orginating in the environment and outside of an individual's original gene set. A new study in mice demonstrates that a 'memory' of nutrition during pregnancy can be passed through sperm of male children to their next generation, increasing risk of disease in his grandchildren as well.


The mechanism by which we inherit characteristics from our parents is well understood: half of our genes are from our mother and half from our father.

However epigenetic effects, where a 'memory' of the parent's environment is passed on over generations, are less well understood.

Some understood epigenetic effects are caused by a process known as 'methylation' in which a methyl molecule attaches to DNA and switches genes on or off.


In a study published in the journal Science, an international team of researchers has shown that environmentally induced methylation changes occur only in certain regions of our genome (the 'genome' represents our entire genetic inheritance).


But unexpectedly, methylation patterns are not passed on indefinitely.


Researchers used mice to model the impact of  pregnancy starvation (1) on offspring — as well as to examinine the mechanisms by which this effect was passed down through generations.

The male offspring of an undernourished mother were smaller than average and when fed a normal diet developed diabetes. Strikingly, the second generation offspring of males born to undernourished mothers, were also born small and developed diabetes as adults despite their own mothers never having been undernourished in pregnancy.


"When food is scarce, children may be born 'pre-programmed' to cope with undernourishment. In the event of a sudden abundance in food, their bodies cannot cope and they can develop metabolic diseases such as diabetes.

"We need to understand how these adaptations between generations occur since these may help us understand the record levels of obesity and type 2 diabetes in our society today."


Professor Anne Ferguson-Smith, department of Genetics, University of Cambridge, UK


To see how this effect might be passed on, researchers analysed the sperm in male offspring of under nourished mice, before the onset of diabetes. This window allowed scientists to look at the malnourished pups sperm methylation patterns.

They found that in the malnourished mouse, DNA was less methylated in 111 regions when compared to control, or normal, mouse sperm. These 111 regions tend to be clustered in non-coding regions of DNA – areas of DNA responsible for turning a mouse's genes on or off. They also showed that in the grandchildren mice, genes next to these methylated regions were not functioning correctly – the offspring had inherited a 'memory' of grandmother's under-nutrition.

Unexpectedly however, when the researchers looked at the grandchild's DNA, they found that the methylation changes had disappeared: the memory of the grandmother's under-nutrition had been erased from the DNA – or at least, was no longer being transmitted via methylation.


"This was a big surprise: dogma suggested that these methylation patterns might persist down through generations.

"From an evolutionary point of view, however, it makes sense. Our environment changes and we can move from famine to feast, so our bodies need to be able to adapt.

"Epigenetic changes may in fact wear off. This could give us some optimism that any epigenetic influence on our society's obesity and diabetes problem might also be limited or even reversible."


Dr Mary-Elizabeth Patti, co-author, Joslin Diabetes Center, Harvard Medical School, Boston.


The researchers are now looking at whether epigenetic effects no longer have an impact on great-grandchildren and their subsequent offspring. If it is true that 'you are what your grandmother ate', it might not be true that 'you are what your great-grandmother ate'.

Abstract
Adverse prenatal environments can promote metabolic disease in offspring and subsequent generations. Animal models and epidemiological data implicate epigenetic inheritance, but the mechanisms remain unknown. In an intergenerational developmental programming model affecting F2 mouse metabolism, we demonstrate that the in utero nutritional environment of F1 embryos alters the germline DNA methylome of F1 adult males in a locus-specific manner. Differentially methylated regions are hypomethylated and enriched in nucleosome-retaining regions. A substantial fraction is resistant to early embryo methylation reprogramming, potentially impacting F2 development. Differential methylation is not maintained in F2 tissues, yet locus-specific expression is perturbed. Thus, in utero nutritional exposures during critical windows of germ cell development can impact the male germline methylome, associated with metabolic disease in offspring.


(1) Researchers led by the University of Cambridge and Joslin Diabetes Center/Harvard Medical School, Boston, used mice to model the impact of under-nutrition during pregnancy Male offspring of an undernourished mother were, as expected, smaller than average and, if fed a normal diet, went on to develop diabetes. Strikingly, the offspring of this generation were also born small and developed diabetes as adults, despite their own mothers never being undernourished.

Research was led by the University of Cambridge and Joslin Diabetes Center/Harvard Medical School, Boston; and funded by the Medical Research Council and the Wellcome Trust, UK.

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