Washington: Disrupting steady supply of allopregnanolone (ALLO), a hormone made by the placenta late in pregnancy, to the developing fetus can leave it vulnerable to brain injuries associated with autism spectrum disorder (ASD), revealed a study.
The research was presented at the Pediatric Academic Societies Meeting.
According to the Centers for Disease Control and Prevention, about one in 10 babies is born preterm, before 37 weeks of gestation. Premature birth is a major risk factor for ASD.
The placenta is an essential and understudied organ that is shared by the developing foetus and the pregnant mother, delivering oxygen, glucose and nutrients and ferrying out waste products.
The placenta also delivers ALLO, a progesterone derivative, needed to ready the developing foetal brain for life outside the womb.
ALLO ramps up late in gestation. When babies are born premature, the supply of ALLO stops abruptly. That occurs at the same time the cerebellum – a brain region essential for motor coordination, posture, balance and social cognition- typically undergoes a dramatic growth spurt.
“Our experimental model demonstrates that losing placental ALLO alters cerebellar development, including white matter development. 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,” said Anna Penn, a neonatologist.
The research team created a novel experimental model in which the gene encoding the enzyme responsible for producing ALLO is deleted in the placenta. They compared these preclinical models with a control group and performed whole brain imaging and RNAseq gene expression analyses for both groups.
“We saw long-term cerebellar white matter alterations in male experimental models, and behavioural testing revealed social impairments and increased repetitive behaviours, two hallmark features of ASD. These male-specific outcomes parallel the increased risk of brain injury and ASD we see in human babies born prematurely,” said Claire-Marie Vacher, lead study author.
“Our findings provide a new way to frame poor placental function: Subtle but significant changes in the uterus may set in motion neurodevelopmental disorders that children experience later in life,” said Dr Penn, the study’s senior author.
“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 foetuses,” Penn added.
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