Assisted reproductive technology (ART) has helped millions of families give birth to babies furthering their own genetic lineage, using methods that range from in vitro fertilization through the cryopreservation of gametes. Of course, given the opportunity for errors and the manmade nature of this process, safety is one concern—and yet, as scientist Boris Novakovic notes, “Previous studies have found some epigenetic changes in embryos grown in labs. However, no study has looked for these changes in the same individuals at birth and adulthood…”
To start getting answers about this, Dr. Novakovic and his research team stepped in with their study of 158 Australians (22-35 years of age) who were conceived using ART, whom they compared to 75 individuals who were conceived naturally. Blood samples were collected both when these people were newborns as well as in adulthood. While previous studies have demonstrated no difference in health outcomes between two groups like this, Dr. Novakovic wanted to look at DNA methylation patterns to compare trends at birth with trends in adulthood, and start to understand the epigenetic changes that take place over the course of a lifetime.
This pioneering study measured DNA methylation patterns in the same subjects both at birth and as adults. But why study them at all—what is DNA methylation, and why is it important? As its name may suggest, DNA methylation occurs when methyl groups are added to DNA, changing the way that it coils three-dimensionally, and thus controlling the access cellular machinery has to the DNA. Tampering with access to the DNA effectively changes whether it gets transcribed into RNA and then translated into proteins, resulting in altered gene expression.
Unlike a mutation, which permanently alters the copy in question of the genetic sequence, epigenetic changes can be temporary, although there is evidence that supports some of these changes being capable of being passed on between generations. Given this wide range of possibilities for how epigenetic modifications may impact gene expression, the context of ART provided Dr. Novakovic and his team with a fascinating line of inquiry: how did ART add an additional layer of epigenetic complexity, and how do they evolve as the person ages?
The research team’s findings yielded significant progress in answering this question, since they consistently observed epigenetic variation in genetic material at birth but that gradually wore off by adulthood. Dr. Novakovic is insistent that larger samples sizes are needed in order to more accurately and reliably characterize this—even things like geographic variation could contribute to a better understanding of these processes. One theory about why there is variation at birth has to do with stress or other hormonal signals in the mother’s body, such as ovarian stimulation.
Currently, these epigenetic changes don’t seem to result in any potential health effects across the two different groups. It is not thought that they have major long-term consequences; however, they still represent another potential dial for adjustment. Given that there are some risks for small complications from ART, including low birth weight and preterm birth, it is important to understand where these risks may originate.
Dr Novakovic went on to say, “Our results are reassuring for families as they suggest that environment and lifestyle experienced from birth can repair any epigenetic deviations associated with fertility treatments.” While Dr. Novakovic and his team will go on to expand their research sample size and scope, there is room for others to collaborate and expand on these published findings.
Understanding more about the implications of epigenetic changes—including where they don’t have any observable effects, or whether there is a threshold or timescale at which they do—is critical for understanding yet another layer of how gene expression is controlled. This, in turn, paints a clearer picture of factors affecting how individuals develop as well as factors contributing to disease—and potential avenues for therapeutic intervention.
Novakovic B, et al. “Assisted reproductive technologies are associated with limited epigenetic variation at birth that largely resolves by adulthood Nature Communications 2 Sept. 2019
Murdoch Children’s Research Inst. “Assisted reproduction technology leaves its mark on genes but only temporarily, study shows” MCRI Research News, 3 Sept. 2019