Researchers are investigating placental genes to understand the impact of Assisted Reproductive Technology (ART) on child development. Notable differences were found between placentas from frozen and fresh embryo transfers, along with changes in the function of a gene linked to obesity and type 2 diabetes.
Around one in six couples trying to conceive face infertility challenges. In Finland, over five percent of children are born each year with the assistance of Assisted Reproductive Technology (ART), and globally, ART has helped give rise to over ten million children.
While children conceived through ART are typically healthy, there are slight increases in risks for growth disturbances and conditions such as cardiovascular, metabolic, and neurodevelopmental disorders. It remains unclear whether these risks stem from ART procedures or parental subfertility.
To unravel the molecular mechanisms behind these ART-related risks, researchers from the University of Helsinki and Helsinki University Hospital analyzed newborns and placentas from 80 ART pregnancies and 77 natural pregnancies. This study uniquely considered various ART methods and the sex of the infants.
The placenta serves as a fascinating organ, linking the mother and fetus, mediating environmental influences, and affecting fetal growth.
“The placenta provides an exceptional insight into the early stages of development, which are otherwise hard to study in humans,” says Associate Professor Nina Kaminen-Ahola, the study’s leader at the University of Helsinki.
Frozen embryo transfers mimic natural pregnancies
The researchers examined genome-wide placental gene function and DNA methylation, an important epigenetic marker affecting gene regulation. They also investigated potential links between the observed changes and the weight and height of placentas and newborns.
A key finding highlighted differences between two common ART methods: fresh and frozen embryo transfers. In fresh embryo transfers, the IVF-fertilized embryo is placed directly into the uterus, while frozen embryo transfers involve freezing the embryo for a certain time before transferring it.
Prior studies have indicated that placentas and children from fresh embryo transfers tend to be smaller than their frozen counterparts. This study aligned with those findings, revealing that specific changes in metabolism and growth were noted only in placentas from fresh embryo transfers.
“Nearly all placentas from frozen embryo transfers were implanted into the uterus during the mother’s natural cycle, unlike the artificially induced hormone surge seen in fresh transfers. Thus, pregnancies in these cases resemble spontaneous pregnancies more closely,” explains Pauliina Auvinen, a doctoral researcher involved in the project.
Gene linked to obesity and diabetes shows altered function
The researchers also discovered alterations in a gene known as DLK1. The activity of this gene was diminished in both ART placentas and those from subfertile couples who later conceived spontaneously.
The DLK1 gene plays a role in metabolic regulation and has previously been linked to obesity and type 2 diabetes. It may also contribute to maternal physiological changes during pregnancy.
A previous mouse study indicated that Dlk1 is crucial for a woman’s proper metabolic response while pregnant, facilitating the use of fat for energy and thus supporting fetal growth. Reduced expression of Dlk1 was associated with lower birth weights.
Kaminen-Ahola mentions that low birth weight has similarly been associated with reduced DLK1 expression in humans.
“It’s necessary to further explore the role of this gene in subfertility and the rising prevalence of metabolic conditions like obesity and type 2 diabetes.”
Further research required
Even with these important findings, additional samples are needed to deepen the understanding of how various fertility treatments, subfertility, and infant sex influence child development and health. Moreover, assessing the long-term effects of ART will require ongoing monitoring of the children.
“These results may help refine ART techniques and shed light on the causes of subfertility and infertility. We are continually gathering more samples and appreciate the participation of all families involved in the epiART study,” states Kaminen-Ahola.
