Neuro-toxic and Reproductive Effects of BPA

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 analogues), 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 differentiation, synaptic plasticity, neuroinflammation, 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 Releasing 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 results have emerged in animal models and human. Thus, further studies are needed to better define their safety levels. This review 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.

Histone Post-Translational Modifications and CircRNAs in Mouse and Human Spermatozoa: Potential Epigenetic Marks to Assess Human Sperm Quality

“…These data strongly encourage to include circRNAs in the pool of molecules able to influence sperm quality. Certainly, male fertility is in danger because of environmental pollutants, inadequate diet and lifestyles [268][269][270][271][272]. In addition, several lifestyle pastimes such as alcohol, tobacco and marijuana have been shown to have further negative effects on male reproduction [270].…”

Environmental Impact on Male (In)Fertility via Epigenetic Route

“…BPA, perhaps the most studied compound in this context [ 171 , 172 ], can be found in contaminated food and water and released from industrial products by various physical or chemical processes, including heating, aging, light exposure and/or contact with either acidic or alkaline compounds [ 173 ]. Apart from being detected in many biological fluids, more than 90% of human urine samples contain traceable amounts of BPA [ 174 ], indicating the importance of analyzing BPA-induced health effects.…”

“…Tavares et al [ 141 ] summarize all these effects, highlighting that mammals are exposed to a multitude of environmental EDCs that might have synergistic deleterious effects on sperm physiology [ 141 ]. Interestingly, most effects on sperm quality and fertility are a direct consequence of an intratesticular environment disrupted also in the presence of low doses of BPA [ 171 , 172 ]: testes of rats neonatally exposed to BPA show perturbations in Sertoli cell junctional protein payload, important to create a correct progression of germ cells and, therefore, SPZ of good quality [ 199 , 200 ].…”

Minireview: The Epigenetic Modulation of KISS1 in Reproduction and Cancer

“…The main actor is the hypothalamic GnRH, which is secreted in a pulsatile manner to target the pituitary gland, thus inducing the secretion of pituitary gonadotropins (follicle-stimulating hormone (FSH) and luteinizing hormone (LH)), the downstream production of sex steroids by gonads, and the progression of gametogenesis [26]. Environmental factors like diet and nutritional status, endocrine disrupting chemicals, stress, or intensive physical training may affect the functionality of the HPG axis with consequences on reproductive ability [15,27,28,29,30,31]. In this respect, several neuronal networks catch and integrate exogenous and endogenous environmental “cues”, thus modulating the activity of GnRH-secreting neurons.…”