A study of placenta genes reveals the impact of artificial insemination on child development.
Although children conceived through ART are generally healthy, there is a noted slightly elevated risk of growth disorders, as well as cardiovascular, metabolic, and neuro-psychological disorders. The underlying causes of these risks, and whether they result from ART procedures or parental infertility, remain unknown.
To understand the molecular mechanisms of the risks associated with ART, researchers from the University of Helsinki and Helsinki University Hospital studied newborns and placentas collected after 80 ART procedures and 77 spontaneous pregnancies. For the first time, various ART methods and the sex of the children were considered when comparing the placentas.
The placenta proved to be an extremely interesting organ that connects the mother and fetus, mediates environmental influences on the child, and impacts fetal development.
“The placenta opens a unique window into the earliest stages of development, which are otherwise difficult to study in humans,” says Associate Professor Nina Kaminen-Ahola, the lead researcher at the University of Helsinki.
The study has been published in the journal Communications Medicine.
The genomic functions of placental genes and DNA methylation—the most recognized epigenetic mark involved in gene regulation—were examined. Additionally, potential links between the observed changes and the weight of the placenta, as well as the weight and growth of the newborns, were explored.
One of the most intriguing findings concerned two widely used ART methods—fresh and frozen embryo transfers. In fresh embryo transfer, the fertilized embryo resulting from IVF is transferred directly from the culture dish to the uterus, while in frozen embryo transfer, the embryo is frozen for a specific period before transfer.
Several studies have found that placentas and children born from fresh embryo transfers are, on average, smaller than those born from frozen embryo transfers. This was also observed in the current study. Specifically, it was noted that the changes related to metabolism and growth were characteristic only of placentas obtained from fresh embryo transfers.
Furthermore, the researchers identified altered function of the DLK1 gene. The expression of this gene was reduced in placentas obtained from ART as well as in placentas from pregnancies of subfertile couples who sought fertilization but conceived spontaneously.
The DLK1 gene regulates metabolism and has previously been associated with obesity and type 2 diabetes. Additionally, it may play a role in the physiological adaptation of the mother to pregnancy.
According to previous research in mice, Dlk1 is necessary for the proper maternal response to fasting during pregnancy, allowing the switch to fat as an energy source and thereby ensuring fetal growth. The silencing of Dlk1 has also been linked to lower birth weights in offspring.
Kaminen-Ahola notes that silencing of the DLK1 gene has also been associated with low birth weights in humans.
The role of this gene in subfertility and the rising metabolic disorders such as obesity and type 2 diabetes requires further investigation.
Despite significant new findings, more samples need to be collected to better understand the impact of various infertility treatments, subfertility, and sex on the development and health of children. Additionally, long-term observation of children is necessary to comprehend the long-term effects of ART.
“Based on the results obtained, it will be possible to improve ART treatment methods and understand the causes of subfertility and infertility. We are continuously collecting new samples and sincerely thank all families for their participation in the epiART study,” said the researchers.