Epigenetics: Cutting edge experience of birth

2. November 2009

Stray reports about after-effects on Cesarean children did not damage the popularity of this method so far. The discovery of Swedish researchers might rekindle the discussion – because the genotype of the ones born like that is different from the ones born normal.

More and more women don’t want to deal with the pain any more. Cesarian is the magic word after nine months of nausea, dressing troubles and increasing immobility. In Brazil it is four out of five women, in the US four out of ten and in Germany every third woman. Nonetheless some of them doubt whether they are not creating any disadvantages or risks for their children with that fast birth by scalpel.

Time and again, reports keep appearing in professional literature about Cesarian children suffering more frequently from asthma and other allergies and a larger number of type-1 diabetics was born by Cesarian. A current research at the Stockholm Karolinska Institute makes these women even more insecure: Because the genotype of the infant born allegedly stress-free looks different from the one of their contemporaries. Their DNA is methylated much stronger which means that many genes seem to be turned off which are active during vaginal birth.

Blocked genes after Cesarian

Mikael Norman and his colleagues selected 37 children for their studies, 21 of them born naturally, 16 by a planned voluntary Cesarian. The researchers found an about twenty percent higher methylation in the leucocytes in the cord blood of Cesarian children. After a few days the physicians measured again blood samples of both groups. To the surprise of all the extent of the DNA methylation had adjusted in both study branches.

Those researches show for the first time that in men the epigenetic control on DNA level is active not only in the early embryonic development but also after birth. Until then it was generally accepted that DNA methalyses “whitewash” the cell cluster as a start shortly after fertilization. Exceptions are genes regulated by imprinting. Depending on origin from father or mother those elements then are active in the child. During further differentiation of the embryonic tissue, DNA methyl-transferases supply mainly CG-residues of the DNA but also histones specifically with methyl groups. Influences on these reactions in the mother’s womb thus seem to have effects on the entire life of the child.

Nutrition of the grandparents influence their grandchildren’s health

Already in 2003, the American Randy Jirtle was able to show in the lab that food for pregnant mice ladies influences the color of fur of the offspring depending on its share of transferable methyl groups. But there are also hints that for example hunger during war times influences the health of the grandchildren. Studies in Iceland and in the US state of Utah showed that the DNA is open for epigenetic changes not only in small time slots: During a DNA comparison of 111 test persons in an interval of eleven to sixteen years, nearly every third person had a methylation pattern differing more than ten percent from the one of the previous analysis. The researchers did not see a clear tendency for increase or decrease of the “blocked” DNA though.

But what do those epigenetic varieties in Cesarian children mean now? Whether they have any effects on the health of the carriers or not is completely unknown at the moment. Mikael Norman writes that shortly before birth adrenergic receptors normally are activated in the embryo. An adequate fuel supply is supposed to take care of enough energy for the long oxygen-deficient passage through the birth channel and enable pulmonary respiration afterwards. During a Cesarian prior to labor contractions the slowly increasing push of catecholamine is missing. The newborn feels the stress of a completely new environment from one moment to the next. Whether this could be the background for a higher neonatal morbidity as observed during some studies, nobody knows so far.

Fearless by a methylation antagonist?

It seems to be clear that not only maternal nutrition but also stress during pregnancy cause epigenetic changes. The group around the epigenetics pioneer Moshe Szyf in Quebec in Canada for example found an excessive methylation of the genes for ribosomal RNA in the brains of suicide patients. In those patients with a history of child abuse, the scientists found a lower activity of the glucocordicoid-receptors in the hippocampus in addition to a stronger methylation. With this they confirmed experiments on lab rats. A lack of care made them grow to be frightened animals with a “stress-processing” center in their brains not functioning sufficiently. Last year, the Americans Courtney Miller und Davis Sweatt showed that methylation blockers can prohibit such a hypermethylation and the effects of stress on behaviour on rats as well.

So does the Cesarean make the newborns grow to be frightened and delicate children with a higher risk for disorders in later life and even transferring their birth trauma to their children’s children? First of all the researchers want to solve the riddle around the fast demethylation after birth. Is the different regulation of genes relevant at all for that short time slot? Which genes does the little organism turn on and off anyway?

“The publication” writes Szyf in a comment on Norman’s article, “allows a first insight in the dramatic meaning changed environmental conditions as they occur during delivery on our epigenome. Epigenetics seem to be the hidden link between influences in the early life and disturbances in older age.” Thus it would be – according to the professor from Montreal – also the basis for the discovery of the mysterious connections between social and economic conditions and disorders of the body.

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