有机锡的外暴露能引起脊椎动物胚胎的独特畸形,但通过母体传递引起的内暴露毒性还缺乏研究.本文通过显微注射的方式研究了三苯基锡(TPT)、过氧化物酶体增殖体激活受体γ(PPARγ)的激动剂罗格列酮(Rosi)和抑制剂T0070907(C_(12)H_8ClN_3O_3)对热带爪蟾胚胎的发育毒性.将3种化合物注入S1一S2期的胚胎后,胚胎的存活率显著下降,其中5 ng TPT,80 ng Rosi和10 ng T0070907注射组存活率分别为46.9%、42.7%和54.2%.胚胎的体长也受到不同程度的影响,5 ng TPT,80 ng Rosi和20 ng T0070907注射组与对照相比体长分别减少了27%、22%和57%.3种化合物还引起了多样的畸形效应,尤其是头部变小及眼睛畸形.说明PPARγ在热带爪蟾早期胚胎的发育特别是头、眼发育中扮演非常重要的角色.TPT与相近剂量T0070907引起的畸形非常相似,说明TPT的致畸机制可能与PPARγ存在某种关系.另一方面,利用整胚原位杂交检测了注射TPT后S20及S25期胚胎的头、眼部标志基因的空间表达,结果表明bf1、en2、krox20及pax6的表达信号均随TPT剂量增大而逐渐变弱且区域变小,定量PCR进一步验证了TPT能在神经胚及早期尾牙期之前影响胚胎头、眼标志基因的表达.研究结果表明,TPT的内暴露对脊椎动物胚胎具有较强的致畸效应和神经毒性.
Xenopus tropicalis embryos were exposed for 48 hr to the mixtures of 5 μg Sn/L triphenyltin （TPT）, which is a well-known endocrine disruptor, and 0.25-5 μg/L 9-cis retinoic acid （9c-RA）, which is the natural ligand of retinoid X receptor. The phenotypes induced by combined exposure were more variable than those resulting from single exposure to either TPT or 9c-RA. The prominent phenotypes included underdeveloped head structures, abnormal eyes, narrow fins, enlarged proctodaeum, etc. Especially, combined exposure induced unexpected notochord malformations, which ranged from small swellings of the surface of the tails to the extension and extrusion of notochord out of the posterior tails. Compared with the 5 μg Sn/L TPT-treated group, the index of fin deficiency was not affected, and the index of axis deficiency was significantly increased with increasing RA concentrations in the mixtures. Our results suggest that combined exposure to TPT and 9c-RA induced not only more variable phenotypes of malformations than exposure to single compound but also some new and unexpected phenotypes.
