Abstract
Phthalates have been widely studied for their reprotoxic effects in male rodents and in particular on testosterone production, for which reference doses were established. The female rodent brain can also represent a target for exposure to these environmental endocrine disruptors. Indeed, a large range of behaviors including reproductive behaviors, mood-related behaviors, and learning and memory are regulated by sex steroid hormones. Here we review the experimental studies addressing the effects and mechanisms of phthalate exposure on these behaviors in female rodents, paying particular attention to the experimental conditions (period of exposure, doses, estrous stage of analyses etc.). The objective of this review is to provide a clear picture of the consistent effects that can occur in female rodents and the gaps that still need to be filled in terms of effects and mode(s) of action for a better risk assessment for human health.
Highlights
Phthalates are among the most abundant organic pollutants in the environment [1], due to their extensive use in the plastic industry
Beyond the reduced testosterone production reported for phthalate exposure and used to establish the reference doses for these molecules, the female brain can represent a sensitive target for these environmental chemicals
While measurement of circulating levels of sex steroids and brain expression of their receptors is generally performed in parallel in the studies assessing reproductive behaviors, this is not always the case for the other behaviors
Summary
Phthalates are among the most abundant organic pollutants in the environment [1], due to their extensive use in the plastic industry. Here we aim to review the experimental studies addressing the behavioral effects and underlying mechanisms of phthalate exposure in female rodents, with a particular focus on behaviors known to be induced or modulated by sex steroid hormones (reproductive and mood-related behaviors and learning and memory). Changes in hormonal levels or their signaling pathways following exposure to endocrine disrupting compounds (EDCs) can lead to long-term or transient modifications in these processes and in behavior In this context, previous reviews addressed the effects of exposure to EDCs, including phthalates, on social and reproductive behaviors [6,7,8], or effects of exposure to phthalates on hippocampal plasticity [9] or the nervous system [10]. Our ultimate goal is to provide a clear picture of the consistent effects that can occur in female rodents and the gaps that still need to be filled in terms of effects and mode(s) of action for a better risk assessment for human health
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