Effects of Gestational Bisphenol A Exposure on Hypothalamic Vasopressinergic Neurons

Background: Bisphenol A (BPA), a well-recognized endocrine disruptor that has been linked to numerous adverse outcomes, is ubiquitously detected in humans, including pregnant women. Emerging epidemiological and animal studies showed associations between prenatal BPA exposure and social-behavioral issues in childhood, including aggression and anxiety. Methods: Since vasopressinergic circuits play important roles in regulating social behaviors, and our previous studies showed that prenatal exposure to BPA altered vasopressin development in offspring, here we evaluated effects of BPA on the number of arginine vasopressin (AVP) neurons in hypothalamic subregions, including the supraoptic nucleus (SON), suprachiasmatic nucleus (SCN) and paraventricular nucleus (PVN), using immunohistochemistry, and assessed the intrinsic electrophysiological properties as well as synaptic transmission of AVP(PVN) neurons using whole-cell patch-clamp. Results: We observed increased number of AVP neurons in SON, SCN, and PVN in BPA treated group compared with the control group. Lower spontaneous action potentials the frequency was found in the BPA group compared to the control group, demonstrating disruption in AVP biophysical properties. Current clamp experiments also showed that BPA treated AVP(PVN) neurons were less responsive to current injections than control AVP(PVN) neurons, including fewer neuronal spikes, delayed latency to the first spike, and less responsive overall were observed in the BPA group. Spontaneous excitatory postsynaptic currents frequency but not amplitude was also altered by BPA gestational exposure, while no significant changes were found for spontaneous inhibitory post-synaptic currents. Conclusion: Collectively, our results suggest that gestational BPA expose might disturb hypothalamic AVP circuits, as indicated by increased AVP neurons in hypothalamic nuclei and disrupted excitability and synaptic transmission of/onto AVP neurons.