Gestational exposure to perfluorooctanoic acid (PFOA): Alterations in motor related behaviors

Abstract

Perfluoroalkyl and polyfluoroalkyl substances are used in commercial applications and developmental exposure has been implicated in alterations in neurobehavioral functioning. While associations between developmental perfluorooctanoic acid (PFOA) exposure and human outcomes have been inconsistent, studies in experimental animals suggest alterations in motor related behaviors. To examine a dose-response pattern of neurobehavioral effects following gestational exposure to PFOA, pregnant CD-1 mice received PFOA (0, 0.1, 0.3, 1.0 mg/kg/day) via oral gavage from gestational day 1–17 and the male offspring examined. Motor activity assessments on postnatal day (PND)18, 19, and 20 indicated a shift in the developmental pattern with an elevated activity level observed in the 1.0 mg/kg/day dose group on PND18. In the adult, no alterations were observed in body weights, activity levels, diurnal pattern of running wheel activity, startle response, or pre-pulse startle inhibition. In response to a subcutaneous injection of saline or nicotine (80 µg/kg), all animals displayed a transient increase in activity likely associated with handling with no differences observed across dose groups. Inhibition of motor activity over 18 days of 400µg/kg nicotine injection was not significantly different across dose groups. Hyperactivity induced by 2mg/kg (+)-methamphetamine hydrochloride intraperitoneal injection was significantly lower in the 1.0 mg/kg/day PFOA dose group as compared to controls. Taken together, these data suggest that the effects on motor-related behaviors with gestational PFOA exposure do not mimic those reported for acute postnatal exposure. Changes were not observed at dose level under 1.0 mg/kg/day PFOA. Further examination of pathways associated with methamphetamine-induced activity is warranted.

Evaluation of Developmental Toxicity, Developmental Neurotoxicity, and Tissue Dose in Zebrafish Exposed to GenX and Other PFAS

“…2018; Hoffman et al 2010;Hoyer et al 2015;Rappazzo et al 2017) and negative (Lyall et al 2018;Rappazzo et al 2017;Stein and Savitz 2011;Stein et al 2013) associations between PFAS exposures and neurodevelopmental outcomes. Similarly, exposure to PFAS has been reported to cause behavioral toxicity in some (Goulding et al 2017;Johansson et al 2008;Long et al 2013;Sato et al 2009;Wang et al 2015), but not all (Butenhoff et al 2009), animal studies. In those studies where a positive relationship was revealed, affected behavioral end points included hyperactivity (Goulding et al 2017;Johansson et al 2009), reduced habituation (Johansson et al 2008), impairments in spatial learning and memory resulting from adult (Long et al 2013) and prenatal exposures (Wang et al 2015), and tonic convulsions in response to an ultrasonic stimulus (Sato et al 2009).…”

“…Similarly, exposure to PFAS has been reported to cause behavioral toxicity in some (Goulding et al 2017;Johansson et al 2008;Long et al 2013;Sato et al 2009;Wang et al 2015), but not all (Butenhoff et al 2009), animal studies. In those studies where a positive relationship was revealed, affected behavioral end points included hyperactivity (Goulding et al 2017;Johansson et al 2009), reduced habituation (Johansson et al 2008), impairments in spatial learning and memory resulting from adult (Long et al 2013) and prenatal exposures (Wang et al 2015), and tonic convulsions in response to an ultrasonic stimulus (Sato et al 2009). Molecular results obtained in animal studies suggest that PFAS exposures may disrupt dopaminergic and/or calcium signaling pathways during neurogenesis (Hallgren and Viberg 2016;Johansson et al 2009;Lee and Viberg 2013;Liu et al 2010aLiu et al , 2010bZeng et al 2011).…”

Per‐ and Polyfluoroalkyl Substance Toxicity and Human Health Review: Current State of Knowledge and Strategies for Informing Future Research

“…Potential adverse effects of PFAS on the nervous system and functions have not been widely investigated. A few studies reported neurotoxicity of PFOS, PFHxS, and PFOA in cell culture systems (Slotkin et al 2008), as well as altered behavioral responses (Goulding et al 2017) and deficits in learning and memory ability in rodents (Viberg et al 2013). In contrast, no significant developmental neurotoxic effects were seen from prenatal exposure to PFOS in USEPA guideline–based studies with rats (Butenhoff et al 2009).…”

Perfluorooctanoic Acid Exposure in Early Pregnancy Induces Oxidative Stress in The Uterus and Liver in Mice

“…Per uorinated compounds (PFCs) have been widely used in many areas, including industrial production, household supplies and even biomedical applications, because of their good chemical stability, and hydrophobic and oleophobic properties (A et al 2020; Kah et al 2020;Li et al 2019b;Sivaram et al 2020). It has been shown that PFCs can be found in the blood, liver, kidney, heart, and muscle, and the toxicity has been demonstrated in the liver (Filgo et al 2015;Wu et al 2017;Zhao et al 2016;Zheng et al 2017), as well as in neuro (Goulding et al 2017), cardiovascular (Lv et al 2018), and reproductive tissues (Lee et al 2017). And it has also been shown to be genotoxic (Butenhoff et al 2014), carcinogenic (Tsuda 2016), and immunotoxic (Di Nisio et al 2020; Liu and Gin 2018).…”