Approximately one in six couples trying to have a child experiences infertility. Although children conceived by Assisted Reproduction are generally born healthy, in recent years a slight increase in the risk of growth disorders, as well as cardiovascular, metabolic and developmental problems, has been observed.
However, the underlying causes of these risks, and whether they arise from the techniques used or from parental subfertility, remain unknown.
To understand the molecular mechanisms behind the risks associated with Assisted Reproduction, researchers from the University of Helsinki and the Helsinki University Hospital examined newborns and placentas from 80 assisted reproduction pregnancies and 77 spontaneous pregnancies.
For the first time, placentas were compared considering the different methods of assisted reproduction and the sex of the children.
The placenta has proven to be an extremely fascinating organ that connects the mother to the fetus, mediates environmental effects on the fetus, and influences its development.
“The placenta offers a unique window into the early stages of development, which are otherwise difficult to study in humans,” says Nina Kaminen-Ahola, leader of the study published in the journal ‘Communications Medicine‘.
The study analyzed placental genetic function at the genomic level and DNA methylation, the best-known epigenetic mark involved in gene regulation.
Possible connections between the observed changes and the weight of the placenta, as well as the weight and height of the newborns, were also studied.
One of the most interesting findings is related to the two methods of most used assisted reproduction: the transfer of fresh and frozen embryos.
In fresh embryo transfer, the in vitro fertilized embryo is transferred directly from culture to the uterus, while in frozen embryo transfer, the embryo is frozen for a variable period before transfer.
Smaller placentas
Several studies have found that placentas and children from fresh embryo transfers are, on average, smaller compared to those from frozen embryo transfers. This was also observed in the current study. Specifically, changes related to metabolism and growth were specific to placentas from fresh embryo transfers.
“Almost all placentas from frozen embryo transfers were transferred to the uterus during the mother’s natural cycle, rather than during an artificial hormonal surge, as occurs with fresh embryo transfers. Therefore, the beginning of pregnancy in these cases is more similar to those spontaneous pregnancies», explains Pauliina Auvinen.
Additionally, the researchers identified an altered function of the DLK1 gene. The expression of this gene was reduced both in placentas from assisted reproduction and in those from spontaneous pregnancies of subfertile couples who had requested fertilization treatment.
The DLK1 gene regulates metabolism and has previously been associated with obesity and type 2 diabetes. It may also play a role in maternal physiological adaptations during pregnancy.
According to a previous study in mice, the Dlk1 gene It is essential for an adequate response to maternal fasting during pregnancy, allowing the use of fat as an energy source to ensure fetal growth. Silencing of this gene was also associated with lower birth weight in offspring.
Kaminen-Ahola notes that silencing of the DLK1 gene has also been linked to low birth weight in humans.
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