Scientists Uncover Surprising Connection Between the Placenta and Autism-Related Brain Development

Could the earliest clues to autism development lie in the placenta rather than the brain? Scientists have discovered that inflammation during pregnancy can disrupt placental development and trigger autism-like traits in male mice, suggesting that certain developmental changes may begin much earlier than previously understood.

Researchers at Cold Spring Harbor Laboratory investigated how maternal immune activation, which occurs when the immune system responds to infection or inflammation, influences fetal development.

Although genetic factors play a major role in autism spectrum disorder, researchers are increasingly examining how environmental and immune-related conditions during pregnancy may contribute to developmental differences.

To investigate this relationship, scientists triggered an immune response in pregnant mice at different stages of gestation using a substance that mimics the body's response to a viral infection without introducing an actual virus.

The findings revealed that fetuses were particularly vulnerable when maternal immune activation occurred on day 12.5 of pregnancy.

Importantly, approximately one-third of the fetuses developed abnormalities within 24 hours of the inflammatory response.

Researchers observed a striking difference between sexes, with developmental abnormalities and subsequent autism-like traits appearing only in male offspring, while female offspring remained unaffected in these experiments.

Further investigation revealed that affected male fetuses showed damage to specialised placental cells called spongiotrophoblasts.

These cells help regulate interactions between maternal and fetal tissues and support the mother's immune tolerance towards the developing fetus.

Researchers suggested that inflammation-related damage to these cells may interfere with the placenta's protective functions, potentially affecting fetal development.

The findings also raise questions about whether female fetuses possess biological mechanisms that provide greater protection against maternal immune activation.

However, the study was conducted in mice, and autism-like behaviours in animals do not directly establish the causes of autism in humans.

REFERENCE: Irene Sanchez-Martin, et al.; Maternal-fetal immune conflict contributes to male-specific impairments in a mouse model of neurodevelopmental disorders. Science Advances, 2026; 12 (38) DOI: 10.1126/sciadv.aeg0779