摘要:
研究孕哺期 BDE 209 暴露对母鼠胎盘和子代脑组织甲状腺激素脱碘酶(deiodinase, DI)基因表达的影响,及其在子鼠神经发育毒性效应中的作用。将 75 只雌性昆明小鼠随机分为对照组、低剂量组和高剂量组,暴露 BDE 209 10 d 后,与雄鼠合笼,每组选取怀孕时间相近(相差不过 2 d)的 8 只母鼠孕期持续染毒至子鼠断乳。采用实时荧光定量 PCR 检测孕 17~18 d 胎盘、出生后 60 d 子鼠脑组织 3种类型脱碘酶基因相对表达; 利用 Morris 水迷宫评价出生后 60 d 子鼠学习记忆能力; 测量第 2、16、30 和 60 天子鼠体重,观察孕哺期BDE 209 暴露对子代生长发育的作用。结果显示,BDE 209 对子鼠出生时体重未见明显影响; 出生后 30 d,高剂量 BDE 209 暴露组雌性子鼠体重显著低于对照组子鼠体重(p <0.05),而低、高剂量暴露组雄性子鼠体重均显著低于对照组子鼠体重(p < 0.05,p < 0.01); 出生后60 d,BDE 209 对子鼠体重影响不明显。BDE 209 暴露能够显著延长出生后 60 d 雌、雄性子鼠逃避潜伏期(p < 0.05 或 p < 0.01)。BDE209 暴露显著降低母鼠胎盘中 3 种类型脱碘酶(主要是 DI-3)基因表达(p <0.05 或 p <0.01); 同时,BDE 209 暴露可诱导出生 60 d 后雄性子鼠脑组织中 DI-1 基因表达(p <0.05 或 p <0.01),抑制雄性子鼠脑组织中 DI-3 基因表达(p <0.05); BDE 209 暴露对出生后 60 d 雌鼠脑组织脱碘酶未见明显影响(p >0.05)。研究结果表明,孕哺期 BDE 209 暴露可能通过影响母鼠胎盘组织脱碘酶(特别是 DI-3)基因表达,导致子鼠神经发育毒性效应-学习记忆能力障碍。
Abstract:
In order to study the effect of BDE 209 exposure on gene expression of deiodinase in placenta of mothers and brain of offspring of mice, 75 Kunming female mice were randomly assigned to control and two experimental groups through gavage for 10 days before mating. Then 8 mice with the similar fertilization day were selected for each group and continued to gavage through pregnancy and lactation, until weaning. Real time RT-PCR was employed to detect the expression of deiodinase mRNA in placenta of mothers at gestational day 17-18 and brain of offspring at 60 days after birth. Morris water maze was used to exam the ability of learning and memory in offspring at 60 days after birth. Body weight in pups exposed to BDE 209 was recorded on day 2, 16, 30 and 60 after birth. Compared with the control group, no significant difference in body weight was found at birth (day 2 and 16). On day 30, the significant decrease was found in female pups in high BDE 209 exposure (p < 0.05), and in male pups exposed to both levels of BDE 209 (p < 0.05). The escape latency of BDE 209 exposure group in postnatal days was longer than the control group, both in male and female mice (p < 0.05 or p < 0.01). Real time RT-PCR displayed that BDE 209 exposure significantly decreased the gene expression of three types of deiodinase in placenta at gestational day of 17-18, especially for DI-3 (p < 0.05 or p < 0.01). DI-1 gene expression was significantly induced by BDE 209 exposure in the brain of male pups at 60 days after birth (p < 0.05 or p < 0.01), while DI-3 expression was significantly decreased in low BDE 209 treated group. No effect in deiodinase gene expression was observed in the brain of postnatal 60 days female pups (p > 0.05). Together, these results indicated that BDE 209 exposure in utero during pregnancy and lactation might damage learning and memory ability in pups, possibly through manipulating the gene expression of deiodinase (mainly in DI-3) in placenta of mothers.
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