Murine neocortical histogenesis is perturbed by prenatal exposure to low doses of bisphenol A

Abstract

Bisphenol A (BPA) has been shown to disrupt thyroid hormone function. We therefore studied whether prenatal exposure to low-doses of BPA affects the morphology and the expression of some genes related to brain development in the murine fetal neocortex. Pregnant mice were injected subcutaneously with 20 microg/kg of BPA daily from embryonic day 0 (E0). Control animals received vehicle alone. For evaluating cell proliferation, neuronal differentiation and migration, bromodeoxyuridine (BrdU) was injected intraperitoneally into pregnant mice with various regimens and the brains were processed for immunohistochemistry. The total RNA was extracted from the embryonic telencephalon at various embryonic stages. The BrdU-labeled cells examined 1 hour after BrdU injection showed no differences between the BPA-treated and control groups (n = 10, each), which indicated that the proliferation of precursor cells was not affected. The BrdU-labeled cells, analysed 2 days after BrdU injection, were decreased in the ventricular zone of BPA-treated mice at E14.5 and E16.5, whereas they were increased in the cortical plate at E14.5 as compared with those in control mice (n = 10, each). Furthermore, the expression of Math3, Ngn2, Hes1, LICAM, and THRalpha was significantly upregulated at E14.5 in the BPA-treated group. These results suggested that BPA might disrupt normal neocortical development by accelerating neuronal differentiation/migration.

Environmental chemicals targeting thyroid

“…138 In addition, BPA exposure alters neocortical histogenesis in the mouse. 139,140 Although no specific link was made to TH action in this study, the findings are consistent with the hypothesis that BPA alters early development of the cortex by interfering with TH signaling.…”

NTP‐CERHR expert panel report on the reproductive and developmental toxicity of bisphenol A

“…Nakamura et al (2006), supported by grants from the Japanese government, examined the effects of prenatal exposure to bisphenol A on the morphology and expression of certain genes related to brain development in the mouse neocortex. In the first experiment ICR/Jc1 mouse dams were injected subcutaneous with either 0 (sesame oil vehicle) or 20 m/kg bw/day bisphenol A [purity not indicated] daily from GD 0 (defined as the day that a vaginal plug was detected) until GD 10.5, GD 12.5, GD 14.5 or GD 16.5.…”

Temporal Effects of Bisphenol A on Dopaminergic Neurons: An Experiment on Adult Rats

“…Impairment by bisphenol A of sexual differentiation of exploratory behavior and the size of the locus coeruleus was also observed [27], and it also increased depression-like behavior [28]. Furthermore, neocortical histogenesis was perturbed by bisphenol A [29]. We have demonstrated that rat hyperactivity was elicited by bisphenol A via both intracisternal administration [4] and oral administration to 5-day-old Wistar pups [5].…”