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Pregnancy Timeline by SemestersDevelopmental TimelineFertilizationFirst TrimesterSecond TrimesterThird TrimesterFirst Thin Layer of Skin AppearsEnd of Embryonic PeriodEnd of Embryonic PeriodFemale Reproductive SystemBeginning Cerebral HemispheresA Four Chambered HeartFirst Detectable Brain WavesThe Appearance of SomitesBasic Brain Structure in PlaceHeartbeat can be detectedHeartbeat can be detectedFinger and toe prints appearFinger and toe prints appearFetal sexual organs visibleBrown fat surrounds lymphatic systemBone marrow starts making blood cellsBone marrow starts making blood cellsInner Ear Bones HardenSensory brain waves begin to activateSensory brain waves begin to activateFetal liver is producing blood cellsBrain convolutions beginBrain convolutions beginImmune system beginningWhite fat begins to be madeHead may position into pelvisWhite fat begins to be madePeriod of rapid brain growthFull TermHead may position into pelvisImmune system beginningLungs begin to produce surfactant
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Epigenetics affects generations

We are more than the sum of our genes. Epigenetic mechanisms, modifications made by environmental cues from our diet, the affects of disease, and a multitude of lifestyle choices, play a major role in prompting DNA to switch genes on and off in us and our children.

It has been long debated if epigenetic modifications accumulated throughout an entire life can affect our children or even grand children. Now researchers from the Max Planck Institute of Immunobiology and Epigenetics in Freiburg, Germany have strong evidence that not only DNA is inherited, but epigenetic instructions we pass down also regulate genes in our children.
New insights from the Lab of Nicola Iovino PhD, describe for the first time a biological consequences of inherited information. His study proves that a mother's DNA memory of an epigenetic influence has become essential to the survival of the next generation.

In our body are more than 250 unique cell types. All contain the exact same DNA bases in exactly the same order. However, liver and nerve cells look very different from each other and perform different functions. What makes the difference between them is the influence of epigenetics.

Epigenetics are forces external to a cell and its DNA. A DNA molecule carries information in a sequence of four nucleotide bases, adenine (A), cytosine (C), guanine (G) and thymine (T), that make up the language of our genome. Short sequences of these letters determine when and where proteins are made in the body. Examples of epigenetic influence are smoking which changes the makeup of lung cells and eventually leads to cancer; while stress, disease or diet can also be stored in the epigenetic memory of cells and influence their performance.

For a long time it was thought these epigenetic modifications never extended into future generations. Scientists assumed epigenetic changes that had accumulated over a lifetime were entirely cleared away during the joining of sperm to egg and development of a new individual. However, a recent handful of studies show epigenetic marks indeed can be transmitted over generations. Exactly how is not fully understood.
"We saw indications of intergenerational inheritance of epigenetic information since the rise of epigenetic [studies] began in the early nineties. For instance, epidemiological studies reveal a striking correlation between the food supply of grandfathers and an increased risk of diabetes and cardiovascular disease in their grandchildren. Since then, various reports suggest epigenetic inheritance exists in different organisms. But molecular mechanisms [for transference] were unknown."

Nicola Iovino PhD, Department of Chromatin Regulation, Max Planck Institute of Immunobiology and Epigenetics, Freiburg, Germany, and corresponding author for the study.

Iovino and his team at the Max Planck Institute of Immunobiology and Epigenetics in Freiburg, Germany use fruit flies to explore how epigenetic modifications are transmitted from mother to embryo. Their recent study focused on a particular modification called H3K27me3 that can also be found in humans. H3K27me3 alters chromatin, the packaging surrounding DNA in the cell nucleus, and is mainly associated with repressing or "turning off" gene expression or function.

The Max Planck researchers found that H3K27me3 modifications that labeled chromatin DNA in the mother's egg cells, were still present in the embryo after it was fertilized even though other epigenetic marks had been erased. "This indicates that the mother passes on her epigenetic marks to her offspring. But we were also interested if those marks are doing something important in the embryo", explains Fides Zenk PhD, first author of the study.

The researchers then used a variety of genetic tools on fruit flies to remove the enzyme that attaches H3K27me3. They discovered that embryos lacking H3K27me3 during early development did not continue developing to the end of embryogenesis. Iovino: "It turned out that, in reproduction, epigenetic information is not only inherited from one generation to another, but is also important to development of the embryo itself".

Looking closer at the embryos, researchers found several important developmental genes, normally switched off during early embryogenesis, were turned on in embryos without H3K27me3. "We assume that activating those genes too soon during development disrupted embryogenesis and eventually caused the death of the embryo. It seems that inherited epigenetic information is needed to process and correctly transcribe the genetic code of the embryo", explains Fides Zenk PhD, Department of Chromatin Regulation, Max Planck Institute of Immunobiology and Epigenetics.

With these results, the study shows a clear biological consequence of inherited epigenetic information. Not only providing evidence that epigenetic modifications in flies can be transmitted across generations, but revealing how epigenetic marks transmitted from the mother can activate genes during early embryogenesis.
"Our study indicates that we inherit more than just genes from our parents. It seems we also get a fine-tuned as well as important gene regulation machinery that can be influenced by our environment and individual lifestyle. These insights can provide new ground for the observation that at least in some cases acquired environmental adaptations can be passed over the germ line to our offspring."

Nicola Iovino PhD

As the disruption of epigenetic mechanisms may cause diseases such as cancer, diabetes and autoimmune disorders, these new findings could have implications in human health.

Gametes carry parental genetic material to the next generation. Stress-induced epigenetic changes in the germ line can be inherited and can have a profound impact on offspring development. However, the molecular mechanisms and consequences of transgenerational epigenetic inheritance are poorly understood. We found that Drosophila oocytes transmit the repressive histone mark H3K27me3 to their offspring. Maternal contribution of the histone methyltransferase Enhancer of zeste, the enzymatic component of Polycomb repressive complex 2, is required for active propagation of H3K27me3 during early embryogenesis. H3K27me3 in the early embryo prevents aberrant accumulation of the active histone mark H3K27ac at regulatory regions and precocious activation of lineage-specific genes at zygotic genome activation. Disruption of the germ line–inherited Polycomb epigenetic memory causes embryonic lethality that cannot be rescued by late zygotic reestablishment of H3K27me3. Thus, maternally inherited H3K27me3, propagated in the early embryo, regulates the activation of enhancers and lineage-specific genes during development.

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Jul 27, 2017   Fetal Timeline   Maternal Timeline   News   News Archive

Egg-cell of a female fruit fly [WHITE ARROW] in which H3K27me3 was made visible by green stain.
This egg cell fused with a sperm, will form one of the next generation of flies. In the upper right corner,
a maternal and paternal pre-nucleus are depicted before fertilization. The green color of H3K27me3
appears exclusively in the maternal pre-nucleus, indicating epigenetic instructions are inherited
into the next generation. Image credit: MPI of Immunobiology a. Epigenetics/ Fides Zenk PhD

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