Placental function related to brain damage associated with autism

Allopregnanolone (ALLO), a hormone produced by the placenta at the end of pregnancy, is a neurosteroid so powerful that disrupting its ongoing supply to the developing fetus can make it vulnerable to brain damage associated with the spectrum disorder of the developing fetus. Autism (TSA), according to the Children's Research presented at the annual meeting of the Pediatric Academic Societies 2019.

In order to more effectively treat vulnerable babies, the Children & # 39; s research team first needed to understand what was wrong with the neat choreography that was pregnancy. According to the Centers for Disease Control and Prevention, about 1 in 10 babies is born prematurely before 37 weeks of gestation. Premature birth is a major risk factor for ASD.

The placenta is an essential organ and little studied, shared by the developing fetus and the pregnant woman, who brings oxygen, glucose and nutrients and transports the waste. The placenta also delivers ALLO, a derivative of progesterone, needed to prepare the developing fetal brain for life outside the uterus.

ALLO is preparing late in the gestation. When babies are born prematurely, their intake of ALLO stops abruptly. This occurs at the same time as the cerebellum – a brain region essential for motor coordination, posture, balance and social cognition – usually experiences a dramatic growth spurt.

"Our experimental model demonstrates that the loss of a placental ALLO alters cerebellar development, including white matter development," explains Anna Penn, MD, Ph.D., neonatologist in the divisions of neonatology and medicine Fetal and Neuroscientific Development at Children's National. "The development of the cerebellar white matter occurs primarily after the birth of babies, so it is particularly striking to note a change in placental function during pregnancy with persistent effects on the subsequent development of the brain."

The research team has created a new experimental model in which the gene coding for the enzyme responsible for producing ALLO is deleted in the placenta. They compared these preclinical models to a control group and performed whole brain imaging analyzes and RNAseq gene expression for both groups.

"We observed long-term changes in cerebellar white matter in male experimental models and behavioral tests revealed social unrest and increased repetitive behaviors, two hallmarks of ASD," says Claire-Marie Vacher, Ph. D., lead author of the study. "These men-specific findings parallel the increased risk of brain damage and ASD seen in prematurely born babies."

ALLO binds to specific GABA receptors, which control most of the inhibitory signals in the nervous system.

"Our findings provide a new way to frame poor placental function: subtle but important changes in the uterus can trigger neurodevelopmental disorders that children experience later in life," says Dr. Penn, lead author of # 39; study. "Our future research could include the identification of new targets in the placenta or brain that could lead to hormone supplementation, thus opening up the possibility of earlier treatment of high-risk fetuses."

---

---

More information:
Presentation of the 2019 Annual Congress of Pediatric Academic Societies: "The loss of placental allopregnanolone alters postnatal cerebellar development and function."