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Fruit of the Womb
Fruit of the Womb

More from the 2007 Society for Maternal-Fetal Medicine Meeting in San Francisco

There were several very interesting presentations today at the Annual SMFM Meeting in San Francisco. Two of these described animal experiments that will undoubtedly have an impact on how we approach the management of certain medical and genetic conditions in humans.

The first was an outstanding presentation by Dr. Kjersti Aagaard-Tillery who is currently at the University of Utah. She was a resident in OB/GYN while I was at the University of Minnesota and is a rising star in basic research in Maternal-Fetal Medicine. Let me be the first to predict that her work will result in major contributions to the understanding and treatment of many chronic medical conditions in humans and worldwide recognition for her accomplishments (hear me out Nobel prize committee; keep an eye on this young one). Anyway, she presented powerful evidence that confirms that the environment to which the fetus is exposed (in this case, decreased uterine blood flow resulting in intrauterine growth restriction) results in permanent ‘programming’ of the fetus that sets it down a pathway that culminates in adult metabolic diseases associated with obesity, diabetes, hyperlipidemia, and hyperinsulinemia.

This programming is the result of persistent changes in hepatic (liver) gene expression as the consequence of ‘epigenetic modification in DNA methylation’ that occurs under the stress of the intrauterine environment and, once this occurs, the condition can be passed on to the next generation of offspring. (This ‘methylation’ results from the same pathways we referred to in yesterday’s discussion of fetal heart malformations and aberrations of folic acid metabolism). Yes, Mathilda, in addition to your genetic background, in some ways we are the product of our (intrauterine) environments.

The most remarkable part of Dr. Aagaard-Tillery’s work (to date), however, is that she and her collaborators were able to completely reverse the phenotypic (fat rats) and biochemical abnormalities associated with these epigenetic modifications by simply placing the animals on a life-long diet rich in the micronutrients (folic acid, choline, vitamin B12, betaine, methionine, arginine, zinc) that are involved catalyzing the biochemical reactions in these metabolic pathways. Perhaps, if we are ever to get serious about attacking the current human epidemic of obesity and its consequences, we need to make sure all folks (from an early age) are provided with a diet rich in these substances. Of course, a little exercise wouldn’t hurt either!

Briefly, the other research that I also thought was absolutely fascinating was presented by Dr. Laura Toso from the National Institutes of Health, Unit on Perinatal and Developmental Neurobiology. Dr. Toso described a mouse model in which the animals carry a chromosomal abnormality that results in a medical condition analogous to Down Syndrome (trisomy 21) in humans. These animals end up with inadequate nerve myelination (myelin is important for rapid transmission of information along nerves), nerve degeneration, developmental delays, and eventually ‘early Alzheimer’s’ disease that is very similar to that seen in Down Syndrome and seems to be associated, at least partly, with insufficiencies of certain biochemicals (neuropeptides) that regulate the release of ‘neurotrophic peptides’ (NAP and SAL for sake of simplicity) that normally help protect nerve cells from this kind of degeneration.

Dr. Toso and her colleagues found that administration of these neurotrophic peptides to the mouse embryos, at a gestational age equivalent to the late first and early second trimesters in humans, resulted in animals with developmental milestones comparable to, if not better in some parameters than, the ‘normal’ and unaffected animals in the control group. Wouldn’t it be amazing if we could give every child with Down Syndrome a shot at a more ‘normal’ life! Makes another pretty good case for getting into a routine of offering ‘combined first trimester screening for aneuploidy’ available to all pregnant women so that we can find these chromosomal abnormalities early, doesn’t it?!?
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