(July 2, 2012) -- In collaboration with scholars at the University of Hawaii at Honolulu and the University of Pennsylvania School of Medicine, researchers from The University of Texas at San Antonio Department of Biology have demonstrated in the laboratory for the first time that primary epigenetic mutations are corrected in the germ (sperm and egg) cells of mice.
The findings are critical because they confirm that environmental factors such as those involved in assisted reproductive technologies (ART) such as in vitro fertilization are likely to induce epimutations, but that these defects are subsequently corrected in the germ cells of the individuals produced by ART and so are not transmitted to subsequent generations.
The epigenome is the genetic programming that is responsible for gene expression, which ultimately decides one's outward appearance. Epimutations typically lead to changes in appearance or cellular function when they disrupt the normal function of one or more genes in a cell.
Over six years, UTSA scholar John McCarrey, the Robert and Helen Kleberg Distinguished Chair in Cellular and Molecular Biology, and two of his graduate students, Eric de Waal and Puraskar Ingale, studied three genes in mice artificially derived through a process called intracytoplasmic sperm injection (ICSI). They observed that half of these mice exhibited epigenetic mutations in their somatic cells.
Previous anecdotal observations had suggested that ICSI-derived mice do not pass on epimutations to their naturally conceived offspring. McCarrey and his collaborators wanted to find definitive evidence confirming this notion.
When the researchers allowed ICSI-derived mice that had epimutations in their somatic cells to breed naturally, they observed that the offspring had no epimuations. Their findings demonstrate that the epigenomes of the parent mice were reprogrammed at some point during the natural reproduction process.
Taken together, the science suggests that ART methods can cause epigenetic defects (epimutations) in the individuals produced by this method, but that if these individuals then reproduce naturally, their offspring will not display similar defects.
"The epigenome is made up of reversible modifications of genetic information, and these modifications are highly susceptible to environmental influences," said McCarrey. "There are more than 4 million humans alive today who were conceived by various forms of ART, and these individuals are at risk of having incurred epimutations during the ART process. The good news is that our data suggest that if these individuals reproduce naturally, their children are not likely to inherit these epigenetic defects."
Assisted reproductive technologies (ART) are becoming increasingly common worldwide and now account for two to three percent of human births. McCarrey and his team are continuing their research in an attempt to optimize ART methods so as to minimize the occurrence of epimutations in these individuals.
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