A new study from Cold Spring Harbor Laboratory has shed light on the origins of autism, revealing a previously unknown connection between inflammation during pregnancy, placental damage, and the development of autism-like traits in male mice. The research suggests that certain developmental disruptions may begin much earlier than previously recognized, offering new clues about autism's origins. The study found that when inflammation occurred 12.5 days into pregnancy, approximately one-third of the mouse fetuses showed developmental abnormalities within 24 hours. Notably, autism-like traits appeared only in male fetuses, while females continued developing normally. This unexpected distinction could provide insight into why autism is diagnosed substantially more often in boys than girls. The researchers examined the placenta, the organ that connects a developing fetus to its mother and supports its growth throughout pregnancy, and found that male fetuses with developmental abnormalities had visible damage to specialized cells called spongiotrophoblasts. These cells play a crucial role in helping the mother's immune system tolerate the developing fetus. The findings suggest that maternal immune activation can interfere with this protective function, leading to harmful effects on the developing fetus. The researchers propose that male embryos may produce distinctive proteins that trigger an unfavorable maternal immune response following a viral infection, or that female embryos possess some form of protection that helps them withstand inflammation during this sensitive developmental period. The study's findings raise important questions about the mechanisms underlying autism development and suggest that biological pathways involved in autism-like development may differ between males and females. Further research is needed to uncover the mechanisms responsible for these contrasting responses and to identify new targets for treatments and early interventions.