Lack of key placental hormone linked to autism development

New research presented at the Neuroscience 2019 annual meeting in Chicago is offering compelling evidence to suggest levels of a steroid hormone called allopregnanolone can affect fetal brain development, and when disrupted can result in cerebral abnormalities and increases in autism risk.

Allopregnanolone is an endogenous neurosteroid known to increase in levels as a woman moves through the stages of pregnancy. Recent research has revealed a synthetic form of allopregnanolone administered to a woman after giving birth can help reduce acute cases of postpartum depression. But, until now it has not been clear what effect this vital hormone has on fetal brain development during pregnancy.

“To our knowledge, no other research team has studied how placental allopregnanolone (ALLO) contributes to brain development and long-term behaviors,” explains Claire-Marie Vacher, lead author on the new research.

“Our study finds that targeted loss of ALLO in the womb leads to long-term structural alterations of the cerebellum – a brain region that is essential for motor coordination, balance and social cognition – and increases the risk of developing autism,”

Investigating the influence of allopregnanolone on brain development, the researchers created an animal model genetically modified to have disruptions to allopregnanolone synthesis. Significant neurodevelopment changes were detected in the animals’ offspring as allopregnanolone production declined.

“From a structural perspective, the most pronounced cerebellar abnormalities appeared in the cerebellum’s white matter,” says Vacher. “We found increased thickness of the myelin, a lipid-rich insulating layer that protects nerve fibers. From a behavioral perspective, male offspring whose ALLO supply was abruptly reduced exhibited increased repetitive behavior and sociability deficits – two hallmarks in humans who have autism spectrum disorder.”

Most interestingly the researchers discovered that these brain development abnormalities could be prevented by administering just one injection of allopregnanolone during an animal’s pregnancy. This implies that the hormone plays a notable role in shaping a fetal brain, and supplements of the compound can prevent abnormalities.