Study Finds That Valproic Acid Exposed Children Had a Higher Risk of Disorder than Non-Exposed Children
Valproic acid (VPA) is a clinical drug used to treat epilepsy and mood disorders. Pregnancy exposure to the medication has been previously associated with a significant increase of autism risk in offspring. This previous research also showed that children who had been exposed to VPA prenatally exhibited core autism spectrum disorder (ASD) symptoms including cognitive and language impairment, neurodevelopmental delay, social difficulties, and behavioral abnormalities. Recently, a team of researchers from China further investigated the effects of VPA on the developing brain by using brain organoids, sometimes referred to as “miniature brains.” Human brain organoids are grown artificially and derived from human cells. The organoids used in this study were made from pluripotent stem cells including human induced pluripotent stem cells (hiPSCs). This research included generating human forebrain organoids (hFOs) from two normal hiPSC lines derived from one male (U1M) and one female (U2F). The study’s design involved exposing hFOs (aged 42 days) to VPA at 1 mM, a clinically relevant concentration for 3 days. The study team then randomly selected hFOs exposed with or without VPA for bulk organoid RNA sequencing and single-cell RNA sequencing. At the end of the research, the study’s authors discovered that VPA exposure in hFOs affected the expression of many ASD risk-associated genes, which led to the disrupted synaptic transmission that has been implicated in the etiology of autism. Ultimately, this study demonstrates that external exposures in pregnancy can cause the same disruptions to gene function as mutations of the genes themselves.
