Epidemiological findings in humans
65 healthy children (mean age 12) born after ART (IVF or ICSI) in Switzerland were compared to 58 control children. All ART children were found to have significantly more rigid arteries as demonstrated in particular by a reduced flow-mediated dilation of brachial artery (mean reduction 25%) and a 30% higher systolic pulmonary artery pressure at high altitude. These findings are consistent with a significantly higher risk of cardiovascular disease at a young age. The observed vascular dysfunctions stem from the ART procedure itself.
Laboratory mice studies
An IVF procedure was developed for mice, replicating the human protocols. The IVF mice were found to present the same abnormalities as observed in the human study. These abnormalities were shown to be caused by epigenetic alterations based on the following findings:
1. The vascular damage was passed on to the offspring of IVF mice.
2. Feeding IVF mice with butyrate, an epigenetic modulator, restored normal arteries in the offspring.
3. Methylation of promoter regions in key genes involved in vasculogenesis and arteriogenesis was shown to be altered.
4. IVF mice presented a significantly shorter life-span when fed a high fat diet.
A few links /references are provided at the end of this summary.
Healthy children born after ART display generalized vascular dysfunction caused by the ART procedure. ART also induces premature systemic vascular dysfunction in mice by an epigenetic mechanism associated with a shortened life
A micro-primer on epigenetic alterations
Each human chromosome is composed of one giant DNA molecule, wherein lies the genetic code, a potentially endless permutation of four nucleotides: A, T, G, C. A particular DNA sequence (a gene), if expressed, contributes to a particular structure or function of the organism. A change in the sequence (a mutation) may result in an altered structure or function and this change is inheritable. Studying all this is the business of genetics.
But heredity is not just the DNA code. There are different hereditary mechanisms that can make genes more or less readable, irrespective of the genetic code.
First of all, each C residue can be methylated, a chemical modification that alters its binding properties. So the same genetic code may not be expressed to the same extent, depending on the level of methylation of the C-s it contains. Methylation/demethylation depends on environmental factors (nutrition, in particular) and other variables, even traumatic events in our lives. It is a reversible mechanism, but it also is inheritable!
The second major alteration concerns histones. Each chromosome is one giant DNA molecule associated with millions of histone and other proteins that make it possible to wrap 2 meters of DNA into each human cell. Histones can be methylated (like C residues), acetylated, and phosphorylates. These chemical alterations change their DNA binding properties and thus the same gene can be expressed differently depending on how histones bind to it. And just like DNA methylation, histone modifications are affected by the environment and are also inheritable.
Studying these and other DNA code-independent inheritable features is the business of epigenetics. Studying epigenetics in humans is quite complex: we don’t have very good tools to obtain full epigenetic profiles in different tissues and identifying epigenetic heredity often means correlating environmental variables in one generation and discovering its impact in descendants in a different environment. But this research is progressing and I believe that some of the findings already made are just the tip of the iceberg.