Toxic PCBs, Sex-Biased Genes and the Developing Brain

Professor Pamela Lein co-authored two new research papers that help explain how biological systems respond to polychlorinated biphenyls (PCBs) exposure, including key differences between males and females.

In two new studies, researchers at the UC Davis MIND Institute have clarified how a long-banned group of chemicals, called polychlorinated biphenyls (PCBs) affect genetic activity. The research helps explain how biological systems respond to these exposures, including key differences between males and females.

“PCBs were banned in the 1970s but are still around us,” said Janine LaSalle, professor in the Department of Medical Microbiology and Immunology, MIND Institute faculty member and senior author on both studies. “PCB chemicals are decreasing in the environment, but surprisingly, low exposure levels aren’t always less hazardous. Higher chemical levels can trigger the body to turn on DNA repair and other stress-related pathways. However, lower levels can slip under the body’s radar and have long-term effects.”

LaSalle and colleagues used PCBs as a lens to better understand developmental biology. The first paper investigated why girls seem to respond differently than boys to some environmental and genetic exposures linked to neurodevelopmental conditions. The second dissected the combined role the MECP2 gene and PCBs play in Rett syndrome.

Together, the two studies provide a more detailed picture of how PCBs influence gene expression and how the body responds.

There are well-documented sex differences in many neurodevelopmental conditions, but the biological mechanism is largely unknown. This research suggests the genetic and epigenetic responses to PCBs differ between males and females, contributing to these differences.”—Pamela Lein, professor and department chair in the Department of Molecular Biosciences, School of Veterinary Medicine

X chromosome defenses

Much of this research was built on the MIND Institute’s MARBLES study. This long-term investigation follows pregnant women who already have an autistic child. Research has shown these younger siblings are more likely to have autism and other neurodevelopmental conditions.

Among its many findings, MARBLES suggested that girls show traits associated with autism and other neurodevelopmental conditions differently than boys, despite similar exposures to genetic or environmental factors. One of the current studies, published in Genome Biology, dove deeper to identify those mechanisms in female and male mouse models.

“There are well-documented sex differences in many neurodevelopmental conditions, but the biological mechanism is largely unknown,” said Pamela Lein, professor and department chair in the Department of Molecular Biosciences in the UC Davis School of Veterinary Medicine and co-author on both papers. “This research suggests the genetic and epigenetic responses to PCBs differ between males and females, contributing to these differences.”

Read More from UC Davis Health and the MIND Institute