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Environ Res. 2018 Jul;164:45-52. doi: 10.1016/j.envres.2018.02.011. Epub 2018 Feb 22.

In vivo maternal and in vitro BPA exposure effects on hypothalamic neurogenesis and appetite regulators.

Author information

1
Perinatal Research Laboratory, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Department of Obstetrics and Gynecology, Torrance, CA, USA; Department of Obstetrics and Gynecology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA. Electronic address: mdesai@labiomed.org.
2
Department of Health and Life Sciences Department of Internal Medicine, Charles R. Drew University, Los Angeles, CA, USA.
3
Perinatal Research Laboratory, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Department of Obstetrics and Gynecology, Torrance, CA, USA.
4
Perinatal Research Laboratory, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Department of Obstetrics and Gynecology, Torrance, CA, USA; Department of Obstetrics and Gynecology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA; Department of Obstetrics and Gynecology, Charles R. Drew University, Los Angeles, CA, USA.

Abstract

In utero exposure to the ubiquitous plasticizer, bisphenol A (BPA) is associated with offspring obesity. As food intake/appetite is one of the critical elements contributing to obesity, we determined the effects of in vivo maternal BPA and in vitro BPA exposure on newborn hypothalamic stem cells which form the arcuate nucleus appetite center. For in vivo studies, female rats received BPA prior to and during pregnancy via drinking water, and newborn offspring primary hypothalamic neuroprogenitor (NPCs) were obtained and cultured. For in vitro BPA exposure, primary hypothalamic NPCs from healthy newborns were utilized. In both cases, we studied the effects of BPA on NPC proliferation and differentiation, including putative signal and appetite factors. Maternal BPA increased hypothalamic NPC proliferation and differentiation in newborns, in conjunction with increased neuroproliferative (Hes1) and proneurogenic (Ngn3) protein expression. With NPC differentiation, BPA exposure increased appetite peptide and reduced satiety peptide expression. In vitro BPA-treated control NPCs showed results that were consistent with in vivo data (increase appetite vs satiety peptide expression) and further showed a shift towards neuronal versus glial fate as well as an increase in the epigenetic regulator lysine-specific histone demethylase1 (LSD1). These findings emphasize the vulnerability of stem-cell populations that are involved in life-long regulation of metabolic homeostasis to epigenetically-mediated endocrine disruption by BPA during early life.

KEYWORDS:

Epigenetic; Neuroprogenitor cells; Obesity; Perinatal exposures; Proliferation, differentiation

PMID:
29476947
DOI:
10.1016/j.envres.2018.02.011
[Indexed for MEDLINE]

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