Abstract

Background: Bisphenol A (BPA) is one of the highest volume chemicals produced worldwide. It has recognized activity as an endocrine-disrupting chemical and has suspected roles as a neurological and reproductive toxicant. It interferes in steroid signaling, induces oxidative stress, and affects gene expression epigenetically. Gestational, perinatal and neonatal exposures to BPA affect developmental processes, including brain development and gametogenesis, with consequences on brain functions, behavior, and fertility.Methods: This review critically analyzes recent findings on the neuro-toxic and reproductive effects of BPA (and its ana-logues), with focus on neuronal differentiation, synaptic plasticity, glia and microglia activity, cognitive functions, and the central and local control of reproduction.Results: BPA has potential human health hazard associated with gestational, peri- and neonatal exposure. Beginning with BPA’s disposition, this review summarizes recent findings on the neurotoxicity of BPA and its analogues, on neuronal dif-ferentiation, synaptic plasticity, neuro-inflammation, neuro-degeneration, and impairment of cognitive abilities. Furthermore, it reports the recent findings on the activity of BPA along the HPG axis, effects on the hypothalamic Gonadotropin Releas-ing Hormone (GnRH), and the associated effects on reproduction in both sexes and successful pregnancy.Conclusion: BPA and its analogues impair neuronal activity, HPG axis function, reproduction, and fertility. Contrasting re-sults have emerged in animal models and human. Thus, further studies are needed to better define their safety levels. This re-view offers new insights on these issues with the aim to find the “fil rouge”, if any, that characterize BPA’s mechanism of action with outcomes on neuronal function and reproduction.

Highlights

  • The main consequence of industrialization is the release of substances capable of interfering in the physiological endocrine function [i.e., endocrine-disrupting chemicals (EDCs)]

  • Beginning with Bisphenol A (BPA)’s disposition, this review summarizes recent findings on the neurotoxicity of BPA and its analogues, on neuronal differentiation, synaptic plasticity, neuroinflammation, neuro-degeneration, and impairment of cognitive abilities

  • It reports the recent findings on the activity of BPA along the HPG axis, effects on the hypothalamic Gonadotropin Releasing Hormone (GnRH), and the associated effects on reproduction in both sexes and successful pregnancy

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Summary

Methods

This review critically analyzes recent findings on the neuro-toxic and reproductive effects of BPA (and its analogues), with focus on neuronal differentiation, synaptic plasticity, glia and microglia activity, cognitive functions, and the central and local control of reproduction

Results
Conclusion
INTRODUCTION
Molecular Mechanisms
BPA Disposition and Metabolism
BPA Compared to BPS
Sex-specific Differences in Disposition and Effects
Effects of BPA on Neurogenesis and Synaptic Plasticity
Effects of BPA on Glia and Microglia
Effects of BPA on Cognitive Functions and Behavior
Neurotoxic Effects of BPA Analogues
THE EFFECTS ON THE HPG AXIS AND THE OUTCOMES ON FERTILITY
The Hypothalamic Activity of BPA on Reproduction
BPA Interference in Energy Intake and Reproduction
Effects on Ovary
Effects on Uterus
Effects on the Placenta
Birth Weight
Preterm Birth
Fetal Malformation
Male Reproduction
CONCLUSION
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