Scientists from the Children’s National Health System (Washington DC, USA) have determined that disruption of allopregnanolone (ALLO) delivery to the fetus during pregnancy can increase the likelihood that the child is born with autism spectrum disorder (ASD).
Their findings were presented at the Pediatric Academic Societies’ Annual Meeting 2019 (24 April–1 May, Baltimore, MD, USA).
ALLO plays a role in preparing the fetal brain for neonatal life. Levels of the progesterone derivative rise towards the end of gestation.
Premature birth is a major risk factor for brain injury and ASD, and as premature birth abruptly stops exposure of the fetus to ALLO, there could be a link between ALLO supply and brain development.
To investigate this link, the study utilized a genetically modified animal model in which an enzyme involved in synthesizing ALLO could not be produced in the placenta. Whole-brain imaging and RNAseq gene expression analyses were then performed on the male neonates.
Comparison of the results with those of control animals demonstrated that the loss of placental ALLO altered development of the cerebellum and the white matter within it.
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“Cerebellar white matter development occurs primarily after babies are born, so connecting a change in placental function during pregnancy with lingering impacts on later brain development is a particularly striking result,” commented Anna Penn (Children’s National Health System).
To test for symptoms of ASD, the scientists also performed behavioral studies on the animals.
“Behavioral testing revealed social impairments and increased repetitive behaviors, two hallmark features of ASD,” explained Claire-Marie Vacher (Children’s National Health System). “These male-specific outcomes parallel the increased risk of brain injury and ASD we see in human babies born prematurely.”
“Our findings provide a new way to frame poor placental function, subtle but significant changes in utero may set in motion neurodevelopmental disorders that children experience later in life,” added Penn.
The researchers hope that a better understanding of how fetal development can go wrong will allow the development of more effective treatments for infants who are vulnerable to brain damage and ASD.
“Future directions for our research could include identifying new targets in the placenta or brain that could be amenable to hormone supplementation, opening the potential for earlier treatment for high-risk fetuses,” concluded Penn.
Source: EurekAlert. Placental function linked to brain injuries associated with autism. Press release: www.eurekalert.org