A new animal study has found that prenatal exposure to bisphenol A — a chemical commonly found in plastics — can lead to lasting brain changes and behavior associated with schizophrenia. The research, published in Physiology & Behavior, revealed that female rats exposed to BPA in the womb showed impaired sensorimotor function and a reduction in key brain cells linked to psychiatric illness. Surprisingly, however, male rats were unaffected.
Bisphenol A, or BPA, is a synthetic compound widely used in manufacturing polycarbonate plastics and epoxy resins. These materials appear in everyday items such as food containers, water bottles, the lining of metal cans, and thermal paper receipts. BPA can leach from products and enter the human body through ingestion, skin contact, or inhalation. Studies have detected BPA in the blood, urine, and tissue of more than 90 percent of people tested, including pregnant women. BPA also crosses the placenta and blood-brain barrier, meaning it can reach the developing brain during pregnancy.
BPA is known to interfere with hormone systems and is considered an endocrine-disrupting chemical. Because of its widespread presence and links to health concerns, BPA has become the focus of major scientific and regulatory efforts. The U.S. National Toxicology Program, along with the Food and Drug Administration and the National Institute of Environmental Health Sciences, established the CLARITY-BPA project to better understand its biological effects.
The developing brain is particularly sensitive to environmental toxins, and prenatal exposure to endocrine disruptors like BPA may permanently alter brain structure and function. Previous studies have linked early BPA exposure to problems with learning, memory, mood, and social behavior in animals, and to neurodevelopmental disorders such as anxiety, depression, and autism in humans.
Some research has also raised concerns about a possible link between BPA and schizophrenia, a severe mental disorder involving hallucinations, delusions, and disrupted thinking. One theory of schizophrenia points to dysfunction in a specific set of brain cells that use the chemical messenger GABA. These cells include parvalbumin-positive interneurons in the prefrontal cortex — a brain region central to planning, decision-making, and social behavior.
Given this background, the researchers set out to test whether prenatal BPA exposure could affect markers of schizophrenia in rats, including behavior linked to psychosis and changes in GABA-related brain genes and cells.
Scientists at the Iran University of Medical Sciences used pregnant Sprague-Dawley rats and assigned them to one of four groups. From the first day of pregnancy until delivery, each group received a daily oral dose of either low-dose BPA (0.25 mg/kg), high-dose BPA (2.5 mg/kg), a reference estrogen (ethinyl estradiol), or a control solution.
After birth, the pups were raised by their mothers and weaned at three weeks old. They were housed until early adulthood. On days 62 and 63 after birth, both male and female offspring were tested for behavioral changes. Researchers examined two main outcomes: locomotor activity and a test called prepulse inhibition (PPI), which measures how well the brain filters sensory information. Deficits in PPI are commonly seen in schizophrenia.
On day 64, the researchers collected brain tissue from a subset of the animals. They used immunohistochemistry to examine the density of parvalbumin-positive neurons in the prefrontal cortex. They also used a genetic technique to measure levels of three genes associated with schizophrenia: GAD67, NRG1, and ERbB4.
Female rats exposed to either dose of BPA in the womb showed a significant drop in PPI, indicating impaired sensorimotor gating. This deficit was not seen in male rats or in those exposed to the reference estrogen. PPI is often used in animal models to assess psychotic-like behavior, and reductions in this measure have been linked to schizophrenia-like brain dysfunction.
The researchers also found a sharp reduction in the number of parvalbumin-positive neurons in the prefrontal cortex of female rats exposed to BPA. These neurons play a key role in controlling brain rhythms and maintaining the balance between excitatory and inhibitory signals. Loss or dysfunction of these cells has been consistently reported in the brains of people with schizophrenia.
Interestingly, BPA exposure did not significantly change the expression of GAD67, NRG1, or ERbB4 — genes involved in GABA signaling and neural development — in either male or female rats. Nor did it affect general locomotor activity in either sex.
These results suggest that BPA may disrupt the development or survival of specific neuron types in a sex-dependent way, without altering all aspects of GABAergic gene expression.
Although this study did not find changes in the three measured genes, other research has shown that BPA can interfere with multiple brain development pathways. BPA has been found to affect neural stem cells, reduce cell proliferation and differentiation, and disturb important growth signals such as the Wnt/β-catenin and BDNF pathways. These disruptions may impair neurogenesis and synaptic development during key stages of brain formation.
The current study adds to this body of work by linking prenatal BPA exposure to long-lasting structural and functional changes in a brain region implicated in schizophrenia. The authors suggest that BPA’s hormone-like activity may interfere with estrogen receptor signaling, which plays a role in brain development and is different between males and females.
The researchers acknowledged several limitations. First, they focused only on the prenatal period, although postnatal exposure could also influence brain outcomes. Second, they examined the rats in early adulthood but did not assess whether the effects emerged earlier or evolved over time. Third, only two BPA doses were tested. Other effects might be found with lower or higher exposures. Finally, the analysis of brain tissue was limited to a small number of thin sections, which may not reflect the full extent of changes in the prefrontal cortex.
Even so, the findings point to a potential mechanism by which prenatal BPA exposure could increase the risk of schizophrenia-related features, at least in females. Future research should explore how BPA influences other brain regions and behavioral systems, and whether similar effects occur in other species, including humans.
The study, “Prenatal exposure to Bisphenol A sex-specifically disrupts prepulse inhibition and decreases parvalbumin-positive neurons in the prefrontal cortex of adult rats,” was authored by Abdolhakim Ghanbarzehi, Soraya Mehrabi Abbas Piryaei, Fereshteh Azedi, Ali Mohammadi, and Ali Shahbazi.
