Bisphenol a causes malformation of the head region in embryos of Xenopus laevis and decreases the expression of the ESR-1 gene mediated by notch signaling
Bisphenol a causes malformation of the head region in embryos of Xenopus laevis and decreases the expression of the ESR-1 gene mediated by notch signaling
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DOI：
10.1248/bpb.30.371
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发表时间：
2007-02-01
影响因子：
2
通讯作者：
Kinoshita, Tsutomu
中科院分区：
文献类型：
--
作者：
Imaoka, Susumu;Mori, Tomohiro;Kinoshita, Tsutomu
双酚A（BpA）广泛用于工业和牙科。研究了其对非洲爪蟾胚胎发育的影响。用BpA处理10.5期的爪蟾胚胎。在第35期观察到发育异常;头部区域畸形，包括眼睛和脊柱侧凸。用逆转录-聚合酶链反应（RT-PCR）检测胚胎发育的几个标志物的表达。使用泛神经标记物SOX-2、神经干细胞标记物nrp-1、中胚层标记物MyoD和内胚层标记物sox 17 α。虽然标记基因的表达没有改变治疗与BpA，Pax-6，一个关键的调节器的眼睛的形态发生，减少了BpA。Pax-6是Notch信号传导的下游因子。因此，在BpA存在下研究了典型的Notch依赖性因子ESR-1的表达。BpA能有效抑制ESR-1的表达。全标本原位杂交（whole mount in situ hybridization，WISH）结果显示，Pax-6在中枢神经系统和眼部均有表达。用BpA处理时表达完全丧失。ESR-1在中枢神经系统和眼部的表达也随着BpA的治疗而消失。注射Notch的细胞内结构域有效地恢复ESR-1表达的BpA的存在下，虽然注射的配体的notch，德尔塔，没有。这些结果表明，BpA通过破坏Notch信号降低ESR-1的表达。
Bisphenol A (BpA) is widely used in industry and dentistry. Its effects on the embryonic development of Xenopus laevis were investigated. Xenopus embryos at stage 10.5 were treated with BpA. Developmental abnormalities were observed at stage 35; malformation of the head region including eyes and scoliosis. The expression of several markers of embryonic development was investigated by reverse transcription-polymerase chain reaction (RT-PCR). The pan-neural marker SOX-2, the neural stem cell marker nrp-1, the mesodermal marker MyoD, and the endodermal marker sox17 alpha, were used. Although the expression of marker genes was not changed by treatment with BpA, that of Pax-6, a key regulator of the morphogenesis of the eyes, was decreased by BpA. Pax-6 is a downstream factor of Notch signaling. So, the expression of a typical Notch-dependent factor, ESR-1, was investigated in the presence of BpA. The expression of ESR-1 was efficiently suppressed by BpA. In whole mount in situ hybridization (WISH), Pax-6 was expressed in the central nervous system and eyes. The expression was lost completely on treatment with BpA. The expression of ESR-1 in the central nervous system and eyes also disappeared with BpA treatment. Injection of the intracellular domain of Notch efficiently recovered ESR-1 expression in the presence of BpA although injection of a ligand for notch, Delta, did not. These results suggest that BpA decreased the expression of ESR-1 by disrupting the Notch signal.