Perinatal exposure to the pesticide Chlorpyrifos impacts on breathing phenotype in adult mice

Introduction. Chlorpyrifos (CPF) is an organophosphate pesticide, which was widely used in agriculture, gardening, and animal care for pest control. Hence, CPF represents an important food and environment contaminant, that can be transmitted to the fetus via the placenta or to newborns via breastfeeding. CPF acts as a potent acetylcholinesterase inhibitor, and thus its presence may cause excessive levels of cholinergic neurotransmitter at synapses. Since acetylcholine is a neurotransmitter tightly involved in the respiratory regulation (PMID: 19651660), respiratory activity could be influenced by cholinergic hyperstimulation. The perinatal exposure to CPF may impact through different mechanisms on adult health, as recently reported for perinatal exposure to nicotine in mice (PMID: 34903845). Therefore, although its use has been recently banned due to its potential risk for health, the aim of the present study was to explore the long-term effects of perinatal CPF exposure on the respiratory pattern in adult mice. Methods. CPF (5mg/kg per day) or its vehicle (peanut oil) were administered to dams from mating until weaning by intraoral gavage. Pups were never directly treated with CPF. Adult female and male mice (17-18 weeks of age) born to CPF- (female, n=13 and male, n=15) or vehicle-treated (female, n=13 and male, n=13) dams underwent surgery for the implantation of electrodes capable of recording the electroencephalographic and electromyographic signals for the continuous behavioural state monitoring (wakefulness, non-rapid eye movement sleep, rapid eye movement sleep). Following recovery from surgery (7 days), mice were recorded for 8 hours in a whole-body plethysmography chamber for the simultaneous measurement of ventilatory and behavioural signals. Data were analyzed with ANOVA on log-transformed values with sex and treatment as factors and with a threshold for statistical significance set to P < 0.05. Results. The apnea occurrence rate during sleep was increased in mice born from CPF-treated dams with respect to control mice (P = 0.0004) and was higher in females than in males (P = 0.0380), with no significant interaction between treatment and sex (P = 0.8046). Conclusions. These results indicate that perinatal exposure to CPF produced an altered breathing phenotype in adult mice. Thus, humans might likewise exhibit a long-lasting altered reprogramming of breathing patterns during sleep in adulthood.