Murine neocortical histogenesis is perturbed by prenatal exposure to low doses of Bisphenol A.
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.
Nakamura
Keiko
K
Department of Pathology and Applied Neurobiology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Itoh
Kyoko
K
Yaoi
Takeshi
T
Fujiwara
Yasuhiro
Y
Sugimoto
Tohru
T
Fushiki
Shinji
S
D000818:Animals; D000963:Antimetabolites; D001559:Benzhydryl Compounds; D001973:Bromodeoxyuridine; D004968:Estrogens, Non-Steroidal / Q000633:toxicity*; D005260:Female; D005455:Fluorescent Antibody Technique; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D007150:Immunohistochemistry; D051379:Mice; D008813:Mice, Inbred ICR; D019579:Neocortex / Q000166:cytology / Q000196:embryology / Q000254:growth & development*; D010636:Phenols / Q000633:toxicity*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D012313:RNA / Q000096:biosynthesis / Q000302:isolation & purification; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013963:Thyroid Hormones / Q000502:physiology; D015854:Up-Regulation / Q000187:drug effects; D000098826:Bisphenol A Compounds
D000963:Antimetabolites; D001559:Benzhydryl Compounds; D001973:Bromodeoxyuridine; D004968:Estrogens, Non-Steroidal; D010636:Phenols; D012313:RNA; D013963:Thyroid Hormones; C034477:RNA primers; C006780:bisphenol A; D000098826:Bisphenol A Compounds