By Catherine Kastleman, Program Coordinator, Research Translation Core
Here’s some good news: as of 2014, over half of all participants in clinical trials funded by the NIH are female, whereas in the past females have been largely under-represented in such trials. Due to the increased enrollment of women in recent years, scientists are beginning to get a better grasp on the differential effects of sex on disease. But what about preclinical research in animals and cell cultures? Unfortunately, there are still far fewer females than males in these research studies overall. This means that toxicological research may be missing important sex-based differences in how toxic chemicals affect the body, as well as how they affect the determination of sex itself.
Those important, sex-based differences were a focus of the keynote lecture and subsequent research talks at the Integrated Toxicology and Environmental Health Program (ITEHP) Spring Symposium at Duke on Friday, March 24. The symposium, entitled “Developmental Neurotoxicity: Sex Differences in Toxic Effects and Toxic Effects on Sex Differences.” The symposium was co-sponsored by the Duke University Superfund Research Center.
Margaret McCarthy, PhD, of the University of Maryland Medical Center, delivered the keynote lecture, “Neuroepigenetics, Neuroinflammation, and Male Vulnerability.” McCarthy discussed the relatively new trend towards conducting mechanistic studies of microglia, important, non-neuronal cells in the brain, in order to understand toxic effects on the brain. She emphasized that current research continues to support the notion of a “plastic” brain; researchers cannot specifically characterize a brain as either “female” or “male” because of the mosaic-like (versus blended) pattern in distinct regions of the brain. These regions are not uniform across sex and vary in their responses to chemical exposure.
The next speaker was Heather Patisaul, PhD, from North Carolina State University, who encouraged toxicologists to consider the effects of diet and feeding method on study animals as sources of stress and exposure that could impact study results. For example, many lab animals are fed a diet high in soy, which can be a source of estrogenic chemicals called soy isoflavones. Feeding by gavage –a process during which lab rats are force fed through a tube—may also cause significant levels of stress to the animal and can interfere with the observation of effects from chemical exposures. Both the type of feed and method of feeding can impact the outcome of studies on developmental neurotoxicity, and the impacts may be variable based on the sex of the animals.
Duke Superfund Center Project 2 investigator Heather Stapleton, PhD, followed up on this topic with a discussion of her research on endocrine-disrupting flame retardant chemicals. Her research has shown that certain flame retardant compounds differentially accumulate in the placenta based on fetal sex.
Other speakers included University of Rochester researcher Deborah Cory-Slechta, PhD, who discussed the transgenerational effects of lead and prenatal stress on neurodevelopment and Cynthia Kuhn, PhD, of Duke University, who described her research on sex differences and addiction neurobiology.
Dr. Edward Levin, director of the DUSRC Training Core and NBTA investigator, wrapped up with the final talk on developmental nicotine exposure and pesticide exposure, and gave closing remarks on the next steps for understanding neurotoxic responses during development, pointing towards research on previously under-studied toxicants like PAHs as one possible future direction for research. The symposium was well-attended and all presentations were followed with stimulating questions and discussion among presenters, faculty, students, and staff.
The Integrated Toxicology and Environmental Health Program holds environmental health-related seminars every Friday at noon in Field Auditorium at Duke’s Environment Hall.
 Collins, Francis. “NIH Takes Steps to Address Sex Differences in Preclinical Research.” National Institutes of Health webpage. May 13, 2014. https://www.nih.gov/about-nih/who-we-are/nih-director/statements/nih-takes-steps-address-sex-differences-preclinical-research. Accessed March 27, 2017.