Differences between human twins at birth highlight importance of intrauterine environment

Your genes determine much about you, but environment can have a strong influence on your genes even before birth, with consequences that can last a lifetime. In a study published online in Genome Research, researchers have for the first time shown that the environment experienced in the womb defines the newborn epigenetic profile, the chemical modifications to DNA we are born with, that could have implications for disease risk later in life.

Epigenetic tagging of genes by a chemical modification called DNA methylation is known to affect , playing a role in normal development, aging, and also in diseases such as diabetes, heart disease, and cancer. Studies conducted in animals have shown that the environment shapes the epigenetic profile across the genome, called the epigenome, particularly in the womb. An understanding of how the intrauterine environment molds the human epigenome could provide critical information about disease risk to help manage health throughout life.

, both monozygotic (identical) and dizygotic (fraternal), are ideal for epigenetic study because they share the same mother but have their own and amniotic sac, and in the case of identical twins, also share the same genetic make-up. Previous studies have shown that methylation can vary significantly at a single gene across multiple tissues of identical twins, but it is important to know what the DNA methylation landscape looks like across the genome.

In this report, an international team of researchers has for the first time analyzed genome-scale profiles of umbilical cord tissue, cord blood, and of newborn identical and fraternal twin pairs to estimate how genes, the shared environment that their mother provides and the potentially different intrauterine environments experienced by each twin contribute to the epigenome. The group found that even in , there are widespread differences in the epigenetic profile of twins at birth.

"This must be due to events that happened to one twin and not the other," said Dr. Jeffrey Craig of the Murdoch Childrens Research Institute (MCRI) in Australia and a senior author of the report. Craig added that although twins share a womb, the influence of specific tissues like the placenta and umbilical cord can be different for each fetus, and likely affects the epigenetic profile.

Interestingly, the team found that methylated genes closely associated with birth weight in their cohort are genes known to play roles in growth, metabolism, and cardiovascular disease, lending further support to a known link between low birth weight and risk for diseases such as diabetes and heart disease. The authors explained that their findings suggest the unique environmental experiences in the may have a more profound effect on epigenetic factors that influence health throughout life than previously thought.

Furthermore, an understanding of the epigenetic profile at birth could be a particularly powerful tool for managing future health. "This has potential to identify and track early in life, said Dr. Richard Saffery of the MCRI and a co-senior author of the study, "or even to modify risk through specific environmental or dietary interventions."

More information: Gordon L, Joo JE, Powell JE, Ollikainen M, Novakovic B, Li X, Andronikos R, Cruickshank MN, Conneely KN, Smith AK, Alisch RS, Morley R, Visscher PM, Craig JM, Saffery R. Neonatal DNA methylation profile in human twins is specified by a complex interplay between intrauterine environmental and genetic factors, subject to tissue-specific influence. Genome Res doi: 10.1101/gr.136598.111

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JVK
1 / 5 (1) Jul 15, 2012
It appears that 1,532 genes were recruited into endometrial expression during the evolution of pregnancy in placental mammals, which suggests that adaptive evolution for the placental exchange of nutrient chemicals that epigenetically alter the development of one twin differently than another can be traced back to nutrient chemicals in the mother's diet as well as to her levels of stress both of which alter brain development in offspring of mammals. I could trace it back further to ecological, social, and neurogenic niche construction in vertebrates and invertebrates if I thought anyone might understand the implications for the adaptive evolution of our socio-cognitive niche, which is obviously epigenetically altered in the womb. Nevertheless, it's nice to read that evidence suggests the unique environmental experiences in the womb may have a more profound effect on epigenetic factors that influence health throughout life than previously thought. What were the previous thoughts?
antialias_physorg
not rated yet Jul 16, 2012
This has nothing to do with what you describe. The differences described in tha article (and he novelty in this finding) is this: Being connected to the same provider (the mother) should give both twins access to a near identical intrauterine environments, since both are hooked up to the same system (same dietary input, same external influences, etc. )
The data, however, suggests that this is not the case and that the environment varies widely between the amniotic sacs (which is surprising).

This in turn suggests that differences in development of twins do not start after birth but already develop before birth.

The implications are that twin studies are potentialy more error prone than thought because being a twin is no longer a clear cut case of 'nature vs. nurture'.
There seems to be no instance where 'nurture' is even nearly identical.
JVK
not rated yet Jul 16, 2012
Re: There seems to be no instance where 'nurture' is even nearly identical.

I agree. I also attempted to address the reason for this in limited space. Here's more: Even twins have differences in their genetic predispositions that are epigenetically influenced in utero by maternal-fetal chemical exchange. That's why looking at the 'nature vs. nurture' false dichotomy from the perspective on post-natal influences has been a waste of time. Even monozygotic twins, for example, can have genetically predisposed differences in sexual orientation that are epigenetically altered in utero (e.g., by the epigenetic effects of nutrient chemicals on genetically predisposed brain development that is dependent on gonadotropin releasing hormone pulse frequency in mammals, which is also linked postnatally to sexual orientation via the effects of nutrient chemicals on a diet-responsive neurogenic niche in the hypothalamus that also responds to human pheromones. http://dx.doi.org...i0.17338
antialias_physorg
not rated yet Jul 16, 2012
Even twins have differences in their genetic predispositions that are epigenetically influenced in utero by maternal-fetal chemical exchange.

Well, no. Their predisposition is the same (same genetic code). The epigenetic expression differs - but that is not due to predisposition (which is, as mentioned, identical) but because of the differing intrauterine environment.

The novel finding in the article is that the maternal-fetal chemical exchange varies radically between twins in different amniotic sacs. That fact was hitherto unknown.

All the other things you metion are known, but were thought to be identical before birth. That epigenetic effects do not stop at birth isn't new. Our environment (diet, exposure to sunlight, temperature ranges, chemicals, etc.) influnce the expression of proteins our entire lives.
JVK
not rated yet Jul 16, 2012
Re: Their predisposition is the same (same genetic code).

You seem unfamiliar with the concept of genomic imprinting, which ensures that "Even monozygotic twins have differences in their genetic predispositions that are epigenetically influenced in utero by maternal-fetal chemical exchange."

My co-authors and I addressed this fact in our 1996 Hormones and Behavior article: From fertilization to adult sexual behavior http://www.ncbi.n.../9047261

When the authors start with downstream "facts" and try to explain what's happening after-the-fact, most people get confused about cause and effect. I think your comments add to the confusion.

Isn't it more likely that genomic imprinting is causal to in utero differences in the ability of one twin to acquire a better share of the chemicals necessary to ensure its survival and development? The molecular biology of epigenetic effects on intracellular signaling and stochastic gene expression doesn't change.
Tausch
not rated yet Jul 16, 2012
This must be due to events that happened to one twin and not the other," said Dr. Jeffrey Craig of the Murdoch Childrens Research Institute (MCRI) in Australia and a senior author of the report.


The 'events' are cellular. The 'differences' arise from the cellular differences/signaling imparted mutually to each and every 'future' function. Every 'function' recieves in a mutual exchange of biochemical signals BEFORE ANY 'function' is ready to perform the original intent of the function.

This mutual biochemical cellular exchange signaling - 'imprinting' - has been known for many years.
JVK
not rated yet Jul 16, 2012
I was at a conference in 1995 where David Haidt presented his findings, and we included a section on molecular epigenetics in our 1996 paper. Aren't you merely repeated what I said about genomic imprinting?
antialias_physorg
not rated yet Jul 17, 2012
My co-authors and I addressed this fact in our 1996 Hormones and Behavior article: From fertilization to adult sexual behavior

The article you linked to does not contradict what I said at all - it actually affirms it.

Same environment - same expression, different environment - different expression.
JVK
not rated yet Jul 17, 2012
You wrote: "Their predisposition is the same (same genetic code). The epigenetic expression differs..."

Are you saying that genomic imprinting is different due to the intrauterine environment? Is there a model for that?