More than 13 million children worldwide have been born through assisted reproduction. Could the earliest days of life in a laboratory leave a signature in their DNA?
Scientists in China searched for one possible clue and identified a difference involving the genome’s so-called ‘jumping genes’.
Earlier research has indicated that certain health conditions might be marginally more frequent in children conceived using in vitro fertilisation (IVF). Working out the reason, however, is challenging: any effects of treatment must be distinguished from influences including the parents’ health and events during pregnancy.
IVF and LINE-1 jumping genes
Researchers at Sun Yat-sen University focused on sections of DNA referred to as jumping genes. Despite the label, these are not conventional genes.
Certain jumping genes can reproduce themselves, placing their copied sequences in fresh locations within our DNA. The variety investigated in this research is known as LINE-1.
A previous study in mice found that early-life experiences could influence jumping genes in the brain. However, findings in mice cannot reveal what happens to a human embryo during IVF.
Comparing children conceived through IVF
To investigate whether there was a difference, the researchers analysed blood samples from 33 children conceived through IVF and 42 children conceived without fertility treatment.
Most of the samples were taken from umbilical cords at birth, while others came from children between two and five years old.
Overall, children conceived using IVF had a slightly greater quantity of LINE-1 DNA.
The team also assessed whether the finding was linked to the form of fertility treatment used. Some children had been conceived through standard IVF, whereas others were conceived through a technique in which one sperm is injected into an egg.
No distinct difference in LINE-1 quantities was found between these two groups.
The researchers had a further means of examining the question. In three families, they were able to compare a child conceived through IVF with a sibling conceived without fertility treatment.
In each of the three families, the IVF-conceived child had more LINE-1 DNA. Yet, three families are far too small a sample to show that IVF caused the difference.
After dividing the children by sex, the difference was more apparent in girls. Boys displayed a similar pattern, but the finding was less certain. The researchers say a larger sample is required to determine whether this distinction remains consistent.
What the DNA findings cannot yet show
On examining the children’s DNA in greater detail, the team saw that LINE-1 sequences appeared more or less frequently at certain locations in one group than in the other. Some of these locations sat within a broad region of DNA surrounding genes previously associated with the heart, metabolism, the brain and cancer.
Could this account for the health differences described in previous research? Possibly, but this study cannot yet answer that question.
The team did not test whether those genes behaved differently, nor did it track the children to establish whether any later became unwell. At present, the link gives scientists a particular area to investigate next.
The researchers also cannot determine precisely when the difference emerged. They analysed the children’s DNA from blood samples rather than observing jumping genes move within embryos.
Without DNA from both parents, they cannot establish whether specific changes developed in the children or were inherited through the family. Other experiences during pregnancy could also have contributed.
A separate and considerably larger study, published in Nature Medicine, compared the DNA of 8,328 babies with that of their parents. It identified associations between specific fertility-treatment stages and new DNA changes, with some occurring early in development.
That research considered a different type of change, meaning it does not verify the new finding. Nevertheless, it provides further evidence that assisted reproduction could leave a mark.
In the Chinese research, the team has identified a pattern that could allow scientists to pose more precise questions about IVF and early development.
The next task is to determine whether the pattern is seen again in larger groups of families, where it originates and whether it has any effect on children’s health.
The research was published in the American Journal of Obstetrics & Gynecology.
This article was fact-checked by Peter Dockrill and edited by Peter Dockrill. Although we take pride in our process, we are only human. If you notice an error, please let us know.
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