1. Gestational low-dose BPA exposure impacts suprachiasmatic nucleus neurogenesis and circadian activity with transgenerational effects
- Author
-
Deborah M. Kurrasch, Dinushan Nesan, Michael C. Antle, and Kira M. Feighan
- Subjects
medicine.medical_specialty ,Vasopressin ,endocrine system ,medicine.drug_class ,Neurogenesis ,Neurophysiology ,Biology ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Phenols ,Developmental Neuroscience ,Internal medicine ,medicine ,Endocrine system ,Animals ,Circadian rhythm ,Benzhydryl Compounds ,Research Articles ,030304 developmental biology ,0303 health sciences ,Multidisciplinary ,Suprachiasmatic nucleus ,urogenital system ,SciAdv r-articles ,3. Good health ,Androgen receptor ,Endocrinology ,Endocrine disruptor ,Estrogen ,Suprachiasmatic Nucleus ,030217 neurology & neurosurgery ,hormones, hormone substitutes, and hormone antagonists ,Research Article - Abstract
Fetal BPA exposure, even below safe regulatory limits, disrupts the developing hypothalamus and affects behavior and activity., Critical physiological processes such as sleep and stress that underscore health are regulated by an intimate interplay between the endocrine and nervous systems. Here, we asked how fetal exposure to the endocrine disruptor found in common plastics, bisphenol A (BPA), causes lasting effects on adult animal behaviors. Adult mice exposed to low-dose BPA during gestation displayed notable disruption in circadian activity, social interactions, and associated neural hyperactivity, with some phenotypes maintained transgenerationally. Gestational BPA exposure increased vasopressin+ neurons in the suprachiasmatic nucleus (SCN), the region that regulates circadian rhythms, of F1 and F3 generations. Mechanistically, BPA increased proliferation of hypothalamic neural progenitors ex vivo and caused precocious neurogenesis in vivo. Co-antagonism of both estrogen and androgen receptors was necessary to block BPA’s effects on hypothalamic neural progenitors, illustrating a dual role for these endocrine targets. Together, gestational BPA exposure affects development of circadian centers, with lasting consequences across generations.
- Published
- 2020