Gestational Bisphenol A Exposure Impacts Embryonic Hypothalamic Microglia Numbers, Ramification, and Phagocytic Cups

Jessica M Rosin; Nikol Tretiakov; Emily Hanniman; Kiana Hampton; Deborah M Kurrasch

doi:10.3389/fnins.2022.830399

Gestational Bisphenol A Exposure Impacts Embryonic Hypothalamic Microglia Numbers, Ramification, and Phagocytic Cups

Front Neurosci. 2022 Feb 18:16:830399. doi: 10.3389/fnins.2022.830399. eCollection 2022.

Authors

Jessica M Rosin^{1

2

3

4}, Nikol Tretiakov^{1

2

3}, Emily Hanniman^{1

2

3}, Kiana Hampton^{1

2

3}, Deborah M Kurrasch^{1

2

3}

Affiliations

¹ Department of Medical Genetics, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.
² Alberta Children's Hospital Research Institute, University of Calgary, Calgary, AB, Canada.
³ Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada.
⁴ Department of Oral Biological and Medical Sciences, Faculty of Dentistry, University of British Columbia, Vancouver, BC, Canada.

Abstract

Microglia are a resident population of phagocytic immune cells that reside within the central nervous system (CNS). During gestation, they are highly sensitive to their surrounding environment and can alter their physiology to respond to perceived neural insults, potentially leading to adverse influences on nearby neural progenitors. Given that bisphenol A (BPA) itself can impact developing brains, and that microglia express estrogen receptors to which BPA can bind, here we asked whether fetal microglia are responsive to gestational BPA exposure. Accordingly, we exposed pregnant dams to control or 50 mg of BPA per kg diet during gestation to investigate the impact of maternal BPA on embryonic hypothalamic microglia. Gestational BPA exposure from embryonic day 0.5 (E0.5) to E15.5 resulted in a significant increase in the number of microglia present in the hypothalamus of both male and female embryos. Staining for microglial activation using CD68 showed no change between control and prenatal BPA-exposed microglia, regardless of sex. Similarly, analysis of cultured embryonic brains demonstrated that gestational BPA exposure failed to change the secretion of cytokines or chemokines, regardless of embryo sex or the dose (50 μg of BPA per kg or 50 mg of BPA per kg maternal diet) of BPA treatment. In contrast, live-cell imaging of microglia dynamics in E15.5 control and gestationally-exposed BPA hypothalamic slices showed increased ramification of microglia exposed to BPA. Moreover, live-cell imaging also revealed a significant increase in the number of microglial phagocytic cups visible following exposure to gestational BPA. Together, these results suggest that gestational BPA exposure impacts embryonic hypothalamic microglia, perhaps leading them to alter their interactions with developing neural programs.

Keywords: BPA (bisphenol A); embryogenesis; hypothalamus; microglia; phagocytic cups.