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Microglia, the resident macrophages of the brain, are derived from the yolk sac and colonize the brain before the blood-brain barrier forms. Once established, they expand locally and require Colony-stimulating-factor-1 receptor (CSF1R) signaling for their development and maintenance. CSF1R inhibitors have been used extensively to deplete microglia in the healthy and diseased brain. In this study, we demonstrated sex-dependent differences in the microglial response to the CSF1R inhibitor PLX3397. Male mice exhibited greater microglial depletion compared to females. Transcriptomic and flow cytometry analysis revealed sex-specific differences in the remaining microglia population, with female microglia upregulating autophagy and proteostasis pathways while male microglia increased mitobiogenesis. Furthermore, manipulating key microglial receptors by using different transgenic mouse lines resulted in changes in depletion efficacies that were also sex dependent. These findings suggest sex-dependent microglial survival mechanisms, which might contribute to the well-documented sex differences in various neurological disorders., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

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., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)