Autism spectrum disorder risk linked to insufficient placental steroid

Summary: When the hormone allopregnanolone (ALLO) abruptly decreases or stops during pregnancy, children are more likely to develop autism. Researchers report a single ALLO injection during pregnancy can avert the brain abnormalities and social behaviors associated with ASD in experimental mouse models of autism.

Source: Children’s National Hospital

A study in experimental models suggests that allopregnanolone, one of many hormones produced by the placenta during pregnancy, is so essential to normal fetal brain development that when provision of that hormone decreases or stops abruptly – as occurs with premature birth – offspring are more likely to develop autism-like behaviors. A Children’s National Hospital research team reports the findings Oct. 20, 2019, at the Neuroscience 2019 annual meeting.

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

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.

In addition to presenting the abstract, on Monday, Oct. 21, Anna Penn, M.D., Ph.D., the abstract’s senior author, will discuss the research with reporters during a Neuroscience 2019 news conference. This Children’s National abstract is among 14,000 abstracts submitted for the meeting, the world’s largest source of emerging news about brain science and health.

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, a research team led by Children’s National created a novel transgenic preclinical model in which they deleted a gene essential in ALLO synthesis. When production of ALLO in the placentas of these experimental models declines, offspring had permanent neurodevelopmental changes in a sex- and region-specific manner.

This shows myelin in a brain slice
This is myelin, a lipid-rich insulating layer that protects nerve fibers. The image is credited to Children’s National Hospital.

“From a structural perspective, the most pronounced cerebellar abnormalities appeared in the cerebellum’s white matter,” Vacher adds. “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.”

On a positive note, providing a single ALLO injection during pregnancy was enough to avert both the cerebellar abnormalities and the aberrant social behaviors in experimental models.

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.

“Our team’s data provide exciting new evidence that underscores the importance of placental hormones on shaping and programming the developing fetal brain,” Vacher notes.

About this neuroscience research article

Children’s National Hospital
Media Contacts:
Diedtra Henderson – Children’s National Hospital
Image Source:
The image is credited to Children’s National Hospital.

Original Research: The study will be presented at Neuroscience 2019 in Chicago.

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  1. I would be curious to know if the same conclusion could be considered in children who were over due 42 weeks or more.

  2. It is well known that the placenta pours out progesterone in the second and third trimester. Allopregnaneolone is derived from progesterone. Progesterone is also known to be a strong stimulus to myelin production. I have noted that children with autism have high levels of adrenaline and respond dramatically to the lowering of adrenaline by treating the reason the body is releasing it and using a 5% progesterone cream to block adrenaline. The question I have is how would the mice have reacted to the use of progesterone itself rather than allopregnaneolone?
    Michael Platt, md

  3. Just to be clear… diagnosing mice with autism is really projecting a bit. We haven’t even pinned down precise cerebellum differences in humans with autism (wheras some are reported here)… moreover, do we really think that mice have the same neurotypes as people? There’s a lot more to autism than what’s visible from the outside to allistics (e.g., repetitive behaviors or social distinctions). More importantly, it’s been roundly disproved that autism only impacts males. This only impacted males. So….not autism.

    Maybe some kind of sex/gender based instinctual behavior would be more accurately described? Or if you want to extrapolate to people, this article could be just as misleadingly titled “Toxic masculinity linked to insufficient placental steroids” …. and then go on to say that without enough ALLO male mice were less well socialized. Hmmm….

  4. the article again. They used mice when they abruptly reduced the Allo supply. Not an actual child. Omg. So dense.

  5. I would like to know what poor baby suffered because they did not get enough of this hormone.

  6. Please consider investigating whether acetaminophen (APAP, paracetamol) can alter allopregnanolone levels.

    There is evidence that APAP may disrupt hormones and alter placental adaptation to pregnancy. Additionally, cohort data suggests prenatal APAP exposure may increase autism risk.

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