Male rats exposed to the widely used plasticizer di-(2-ethylhexyl) phthalate (DEHP) during early development had increased anxious behavior as adults, according to research presented Saturday at the Endocrine Society’s annual meeting ENDO 2026 in Chicago, Illinois.
Although this study was conducted in rodents, the study suggests that humans exposed to endocrine disruptors before and shortly after birth may experience behavioral changes that last a lifetime.
This study shows that one of the most widely used plasticizers worldwide can induce behavioral changes when exposed to subjects during prenatal and immediate postnatal development, and that this effect persists over long periods of time. ”
Osvaldo Juan Ponzo, MD, Professor of Physiology, Faculty of Medicine, University of Buenos Aires, Buenos Aires, Argentina
DEHP is used in many plastic products to make them more flexible, including medical equipment, toys, shower curtains, and raincoats. Many studies have shown that DEHP and its metabolites interfere with many organ systems in animals and humans, including the reproductive and nervous systems. Scientists at the University of Buenos Aires Faculty of Medicine wanted to examine the effects of DEHP on anxiety-like behavior in adult male rats and see if the inhibitory neurotransmitters gamma-aminobutyric acid (GABA) or testosterone are involved in regulating this behavior.
Pregnant female rats were orally administered DEHP daily from the first day of pregnancy until weaning. After the male puppies reached maturity at 70 days of age, the researchers placed the puppies in an elevated plus maze (EPM) to assess anxiety-like behavior. This test is based on rodents’ natural aversion to open spaces and heights. The EPM is shaped like a plus sign with two open arms and two closed arms. The scientists were able to measure how often and for how long the rats remained in the arms, as well as the length of time they remained motionless, known as freezing time.
Some animals were given a GABA agonist, a molecule that binds and activates GABA, 90 minutes before the EPM test, and others were given testosterone every 48 hours for 14 days before the test. The scientists observed that the DEHP-only group exhibited anxiety-like behavior, spending less time exploring in the open arms and more time in the closed arms of the maze. Also, the freezing time has become longer. However, DEHP rats treated with GABA agonists and testosterone showed opposite properties.
“This study shows that exposure to DEHP early in life can change anxiety-related behaviors, even if you are not exposed to it in adulthood,” Ponzo said. “These neuroendocrine changes can be reversed by treatment with GABA agonists or testosterone.”
