In a new study, researchers found that when hormone allopregnanolone decreases or stops abruptly, offspring are more likely to develop autism-like behaviors.
Allopregnanolone is one of many hormones produced by the placenta during pregnancy. It is very essential to normal fetal brain development.
This is the first research about how placental allopregnanolone (ALLO) contributes to brain development and long-term behaviors.
The research was conducted by a team from the Children’s National Hospital.
According to the Centers for Disease Control and Prevention, about 1 in 10 infants is born preterm, before 37 weeks gestation; and 1 in 59 children has autism spectrum disorder.
ALLO production by the placenta rises in the second trimester of pregnancy, and levels of the neurosteroid peak as fetuses approach full term.
To investigate what happens when ALLO supplies are disrupted, the research team created a novel transgenic preclinical model in which they deleted a gene essential in ALLO synthesis.
They found 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.
When the production of ALLO in the placentas of these experimental models declines, offspring had permanent neurodevelopmental changes in a sex- and region-specific manner.
The team says the most pronounced cerebellar abnormalities appeared in the cerebellum’s white matter.
They found the increased thickness of the myelin, a lipid-rich insulating layer that protects nerve fibers.
Male offspring whose ALLO supply was abruptly reduced exhibited increased repetitive behavior and sociability deficits—two hallmarks in humans who have autism.
The team also found that providing a single ALLO injection during pregnancy was enough to avert both the cerebellar abnormalities and the aberrant social behaviors.
The research team is now launching a new area of research focus they call “neuroplacentology” to better understand the role of placenta function on fetal and newborn brain development.
The lead author of the study is Claire-Marie Vacher, Ph.D.
The study was presented at the Neuroscience 2019 annual meeting.
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