Prenatal and perinatal exposure to Per- and polyfluoroalkyl substances (PFAS)-contaminated drinking water impacts offspring neurobehavior and development.
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2024-03
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Per- and polyfluoroalkyl substances (PFAS) are persistent organic pollutants ubiquitous in the environment and humans. In-utero PFAS exposure is associated with numerous adverse health impacts. However, little is known about how prenatal PFAS mixture exposure affects offspring's neurobehavioral function. This study aims to determine the causal relationship between in-utero PFAS mixture exposure and neurobehavioral changes in Sprague-Dawley rat offspring. Dams were exposed via drinking water to the vehicle (control), an environmentally relevant PFAS mixture, or a high-dose PFAS mixture. The environmentally relevant mixture was formulated to resemble measured tap water levels in Pittsboro, NC, USA (10 PFAS compounds; sum PFAS =758.6 ng/L). The high-dose PFAS load was 3.8 mg/L (5000×), within the range of exposures in the experimental literature. Exposure occurred seven days before mating until birth. Following exposure to PFAS-laden water or the vehicle during fetal development, neurobehavioral toxicity was assessed in male and female offspring with a battery of motor, cognitive, and affective function tests as juveniles, adolescents, and adults. Just before weaning, the environmentally relevant exposure group had smaller anogenital distances compared to the vehicle and high-dose groups on day 17, and males in the environmentally relevant exposure group demonstrated lower weights than the high-dose group on day 21 (p < 0.05). Reflex development delays were seen in negative geotaxis acquisition for both exposure groups compared to vehicle-exposed controls (p = 0.009). Our post-weaning behavioral measures of anxiety, depression, and memory were not found to be affected by maternal PFAS exposure. In adolescence (week five) and adulthood (week eight), the high PFAS dose significantly attenuated typical sex differences in locomotor activity. Maternal exposure to an environmentally relevant PFAS mixture produced developmental delays in the domains of pup weight, anogenital distance, and reflex acquisition for rat offspring. The high-dose PFAS exposure significantly decreased typical sex differences in locomotor activity.
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Marchese, Melissa J, Tianyi Zhu, Andrew B Hawkey, Katherine Wang, Emi Yuan, Jinchen Wen, Sara E Be, Edward D Levin, et al. (2024). Prenatal and perinatal exposure to Per- and polyfluoroalkyl substances (PFAS)-contaminated drinking water impacts offspring neurobehavior and development. The Science of the total environment, 917. p. 170459. 10.1016/j.scitotenv.2024.170459 Retrieved from https://hdl.handle.net/10161/30649.
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Scholars@Duke
![Levin](https://scholars.duke.edu/profile-images/thumbnail200/0099352.jpg)
Edward Daniel Levin
Dr. Levin is Chief of the Neurobehavioral Research Lab in the Psychiatry Department of Duke University Medical Center. His primary academic appointment is as Professor in the Department of Psychiatry and Behavioral Sciences. He also has secondary appointments in the Department Pharmacology and Cancer Biology, the Department of Psychological and Brain Sciences and the Nicholas School of the Environment at Duke. His primary research effort is to understand basic neural interactions underlying cognitive function and addiction and to apply this knowledge to better understand cognitive dysfunction and addiction disorders and to develop novel therapeutic treatments.
The three main research components of his laboratory are focused on the themes of the basic neurobiology of cognition and addiction, neurobehavioral toxicology and the development of novel therapeutic treatments for cognitive dysfunction and substance abuse. Currently, our principal research focus concerns nicotine. We have documented the basic effects of nicotine on learning memory and attention as well as nicotine self-administration. We are continuing with more mechanistic studies in rat models using selective lesions, local infusions and neurotransmitter interaction studies. We have found that nicotine improves memory performance not only in normal rats, but also in rats with lesions of hippocampal and basal forebrain connections. We are concentrating on alpha7 and alpha4beta2 nicotinic receptor subtypes in the hippocampus, amygdala , thalamus and frontal cortex and how they interact with dopamine D1 and D2 and glutamate NMDA systems with regard to memory and addiction. I am also conducting studies on human cognitive behavior. We have current studies to assess nicotine effects on attention, memory and mental processing speed in schizophrenia, Alzheimer's Disease and Attention Deficit Hyperactivity Disorder. In the area of neurobehavioral toxicology, I have continuing projects to characterize the adverse effects of prenatal and adolescent nicotine exposure. Our primary project in neurobehavioral toxicology focuses on the cognitive deficits caused by the marine toxins. The basic and applied aims of our research complement each other nicely. The findings concerning neural mechanisms underlying cognitive function help direct the behavioral toxicology and therapeutic development studies, while the applied studies provide important functional information concerning the importance of the basic mechanisms under investigation.
![Feng](https://scholars.duke.edu/profile-images/thumbnail200/0276528.jpg)
Liping Feng
Liping Feng, MD's research has focused on understanding the mechanisms of pregnancy complications associated with placental development. These works are translated then to the clinical care of women through studies dedicated to identify risk factors and novel biomarkers for early prediction and prevention of adverse birth outcomes.
Dr. Feng devotes her entire career to improving pregnancy outcomes through innovative research. Dr. Feng conducts both basic science/laboratory research, as well as participates in clinical studies. Her laboratory has focused on understanding the mechanisms of placenta-originated pregnancy complications such as preeclampsia and still birth, which are important causes of perinatal and neonates’ mortality and morbidity. Currently, she has three lines of investigation focused on the roles of inflammation/infection, cell aging, and environmental exposure in placental development and subsequent pregnancy complications.
In addition, Dr. Feng has established an international collaboration in Global Women’s Health. She has affiliated with the Duke Global Health Institute (DGHI) and participates in a DGHI research. She has an interest in DGHI education, and service or policy initiatives, including mentoring and teaching graduate and professional students on fieldwork and research.
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