In two recent studies, researchers at UC Davis have shown that the placenta can provide critical information about early changes to the intra-uterine environment that may influence fetal development and ultimately, children’s brains.
The first study, published in Molecular Autism, validated that placental tissue can provide key data on methylation and fetal development. Methylation is one of several chemical changes, known as epigenetics, that change the structure of the DNA, which then alters gene expression, or how genes function. These changes could serve as markers for risk of autism spectrum disorder (ASD). The study identified a highly methylated gene region (DLL1) that may be associated with ASD.
The second paper, published in Environmental Epigenetics, examined which environmental exposures were associated with the largest effects on placental methylation. The study found that pesticides, which have been previously linked to ASD, had the greatest impact.
“We were looking for changes in DNA methylation patterns in the placenta that could be associated with a later diagnosis of autism,” said Janine LaSalle, professor of medical microbiology and immunology and principal investigator on both studies. “It’s a new way of looking at methylation. Maybe the placenta is a good indicator of what’s going on in the brain.”
Data for these papers came from the Markers of Autism Risk in Babies: Learning Early Signs (MARBLES) study of families that have a child with autism. Subsequent children in these families are at a higher risk for ASD than children from families not already affected. Pregnant women complete detailed questionnaires to assess environmental exposures, which are compared to molecular data from placentas. Irva Hertz-Picciotto, professor public health sciences and researcher with the UC Davis MIND Institute, is principal investigator on MARBLES and a co-author on both papers.
In the Molecular Autism study, the researchers examined placental tissue from 24 children with ASD and 23 with typical neurodevelopment. The paper validated that placenta may be a good model to study fetal neurodevelopment and found that the DLL1 gene is highly methylated in placentas from children with ASD.
“That locus is pretty interesting because it regulates fetal brain development,” said Rebecca Schmidt, assistant professor of public health sciences and a co-author on the paper. “It’s thought to control the cell fate decision to proliferate versus differentiate into mature neurons, which happens to be one of the suspect areas in autism.”
The Environmental Epigenetics paper looked at a variety of environmental exposures and compared those to methylation patterns in 47 placentas from children with ASD. Because MARBLES is a prospective study, the accuracy of their reports on pesticide use around the homes is likely higher than in studies where mothers complete questionnaires after the child has been diagnosed.
The study looked at a variety of factors such as smoking, maternal BMI, education, prenatal vitamin and folate intake, and exposure to professionally-applied pesticides.
"We wanted to see which factors changed methylation patterns in the placenta,” said Schmidt, who was the first author on the paper. “The most significant changes in methylation were associated with pesticides.”
The authors caution that both studies had small participant samples. However, as children in MARBLES continue to mature, there will be greater opportunities to validate these results.
Perhaps the most significant finding is that placental tissue – normally discarded after birth – has great potential to help identify infants who may be at higher risk for ASD and perhaps other neurodevelopmental conditions.
"The placenta provides a time capsule of what the fetus was exposed to during pregnancy,” said LaSalle. “If we could assess ASD risk at birth, then early behavioral interventions with young, high-risk kids could really improve their quality of life.”
Other authors on the Molecular Autism paper were Diane I. Schroeder, Florence K. Crary-Dooley, Cheryl K. Walker, Sally Ozonoff and Daniel J. Tancredi, all of UC Davis.
Other authors on the Environmental Epigenetics paper were Diane I. Schroeder, Florence K. Crary-Dooley, Jacqueline M. Barkoski, Daniel J. Tancredi, Cheryl K. Walker and Sally Ozonoff, all of UC Davis.
These studies were funded by the Department of Defense (AR110194), National Institutes of Health (R01ES021707, R01ES025574, P01ES011269, R01ES020392, U54HD079125, UL1-TR000002, P30-ES023513, S10RR029668 and S10RR027303) and the U.S. Environmental Protection Agency (83543201).