Research in mice suggests that genetic mutations in the SLC25A1 gene, which plays a role in placental development, could be behind some congenital heart defects.
Congenital heart defects, structural heart defects present at birth, are relatively common and occur in around one percent of all newborns. Despite this, the reasons they occur are still relatively unclear.
“A rapidly increasing number of studies in mice have suggested that the placenta is involved in the regulation of embryonic heart development,” said lead author Zhongzhou Yang, PhD, from Nanjing University Medical School, whose research group carried out the study, published in the journal Development.
“Unfortunately, the mechanistic insights for deciphering the placenta-heart axis are largely lacking and very few studies have provided clues to this phenomenon.”
Congenital heart defects are known to be common in children with 22q11.2 microdeletion syndrome and so Yang and colleagues decided to use this as a basis for investigating the formation of these heart defects using a mouse model.
The SLC25A1 gene is located in the fragment of chromosome that is lacking in children born with 22q11.2 microdeletion syndrome. Earlier mouse studies suggested this gene may play a role in placental development with potential impacts on the developing heart, so Yang and team focused on the mouse version of this gene to assess its impact on embryo development.
They created models where the protein encoded by this gene was only available in certain tissues to analyze its role more carefully. Notably, mouse embryos lacking the SLC25A1 protein in their hearts did not have heart defects. However, animals with a deficiency of this protein in the placenta had babies with both placental defects and heart defects.
Placentas with an abnormally low level of SLC25A1 protein, as might be seen with a deletion mutation, had low levels of another protein called PSG1. This protein is produced by the placenta and plays a role in developing endothelial cells that play a variety of roles including lining blood vessels.
The research team showed that treating pregnant mice with PSG1 protein was able to reverse some of the effects of low SLC25A1 protein on the embryo heart and placenta. “PSG1 might therefore become a potentially effective drug to help improve placental and heart development of the fetus in the uterus,” Yang said in press statement.
This work is early stage but provides interesting insights into the potential causes of some congenital heart defects and suggests that developing some kind of early treatment could be possible.
