Can maternal obesity really affect the development of the fetus?

A research team has studied how the mother’s body mass index at the beginning of pregnancy influences the molecular patterns of the placenta, and if it can somehow affect the development of the fetus and the subsequent health of children.

The study is the work of researchers from the University of the Basque Country (UPV/EHU) and the Biocruces-Bizkaia Research Institute in the Basque Country.

Most people think that as the fetus grows in the womb, the mother will be the most important factor influencing the future health of the child, which will undoubtedly prevail among all other possible factors. This conviction is widespread in society and much of the research focuses on the characteristics and behaviors of the mother throughout her pregnancy.

This is the case of the new study, in which “the influence of the mother’s body mass index at the beginning of pregnancy on the molecular profiles of the placenta and more specifically on the methylation of the placenta’s DNA (addition of a group formed by one carbon and three hydrogens, in a certain position of the DNA molecule)”, explains Nora Fernández Jiménez, professor at the Faculty of Medicine and Nursing and researcher at the Department of Genetics, Physical Anthropology and Physiology at the UPV/ uh. “This is the largest study on DNA methylation of the placenta carried out to date, with a total of 2,631 pairs of mothers and children from Europe, North America and Australia”, adds Fernández Jiménez.

Contrary to the best-known mutations —substitution of one nucleotide for another in the DNA sequence—, methylation is a modification of DNA that regulates gene expression without altering the sequence. “Recent studies indicate that methylation is the bridge between the intrauterine environment and the fetal genome. For example, due to the environment, the methylation level of a region of the genome may increase. This increase generally leads to the DNA becoming more compact, and consequently, the transcription machinery cannot access these regions and some genes are silenced. The opposite could also occur, that is, that in response to the environment the level of methylation decreases in certain regions of the genome. In this case, the DNA obtains an open conformation, to which the transcription machinery has better accessibility and, therefore, gene expression would increase. In both cases, the sequence remains intact but the genome behaves in one way or another”, explains the UPV/EHU researcher.

José Ramón Bilbao Catalá and Nora Fernández Jiménez, two of the members of the research team. (Photo: Laura López, Communication Office, UPV/EHU)

“In this work we have identified 27 sites where variations in DNA methylation are observed that seem to be specific to the placenta,” says Fernández. It should be remembered that the placenta is a fundamental organ in fetal growth and development, because it is the organ that connects the mother with the fetus and the organ through which the fetus feeds. “Many of these identified sites are close to genes related to obesity and are enriched in metabolic pathways of cancer and oxidative stress. It does not mean that babies born to mothers with obesity problems will develop cancer, but it does mean that the placenta behaves similar to a tumor, it grows very quickly, and that makes us think that there is an impact on the functioning of the placenta and fetal growth”, adds Nora Fernández.

All these results suggest that placental DNA methylation could be one of the mechanisms by which maternal obesity is associated with adverse metabolic health outcomes in childhood, although Fernández cautions that more studies will be needed to corroborate these findings. In addition, Fernández stresses that “no matter how legitimate our research may be, it should not be used to justify the mother’s guilt mantra, since it is very difficult to quantify the influence that mothers and their characteristics and behaviors have over other factors — fathers or mothers’ partners, families, society itself, and the environment—that surround the fetus and the newborn because they have never been investigated so deeply”.

The study is titled “A meta-analysis of pre-pregnancy maternal body mass index and placental DNA methylation identifies 27 CpG sites with implications for mother-child health”. And it has been published in the academic journal Communications Biology. (Source: UPV/EHU)