Department of Psychology, Ben-Gurion University of the Negev, POB 653, Beer-Sheva, Israel.
Zlotowski Center for Neuroscience, Ben-Gurion University of the Negev, POB 653, Beer-Sheva, Israel.
Behav Brain Funct. 2019 Mar 1;15(1):2. doi: 10.1186/s12993-019-0153-3.
Signs of pervasive developmental disorder and social deficits were reported in toddlers and children whose mothers were exposed to organophosphate pesticides during pregnancy. Deficits in social preference were reported in adult male mice exposed to chlorpyrifos on gestational days 12-15. This study aimed (a) to test the hypothesis that adult female and male mice that were exposed prenatally to subtoxic doses of chlorpyrifos would be impaired in social behavior and (b) to determine if prenatal chlorpyrifos altered the expression of transcripts for oxytocin in the hypothalamus. Pregnant mice were treated by gavage with corn oil vehicle or 2.5 mg/kg or 5 mg/kg of CPF on gestational days 12-15. Social preference, social and non-social conditioned place preference tasks were tested in adults. Expression of oxytocin transcripts in hypothalamus was measured by qPCR.
Chlorpyrifos (5 mg/kg on GD 12-15) reduced the innate preference for a conspecific in a dose and sex dependent manner. Adult males exposed prenatally to 5 mg/kg CPF showed a reduction in social preference. Socially conditioned place preference was impaired in offspring of dams treated with either dose of CPF. Non-social appetitive place conditioning was impaired in offspring of dams exposed to 2.5 mg/kg, but not to 5 mg/kg chlorpyrifos. Prenatal chlorpyrifos treatment did not alter the expression of the oxytocin mRNA in the hypothalamus, although expression was significantly lower in females.
Prenatal chlorpyrifos induced innate and learned social deficits and non-specific conditioning deficits in adult mice in a sex-dependent manner. Males showed specific social deficits following the higher dose whereas both males and females showed a more generalized conditioning deficit following the intermediate dose.
在怀孕期间接触有机磷杀虫剂的孕妇的幼儿和儿童中，出现了广泛发育障碍和社会缺陷的迹象。在妊娠第 12-15 天暴露于氯菊酯的成年雄性小鼠中，报告了社会偏好缺陷。本研究旨在：（a）检验假设，即产前暴露于低毒剂量的氯菊酯的成年雌性和雄性小鼠在社会行为方面会受损；（b）确定产前氯菊酯是否改变了下丘脑催产素的转录本的表达。在妊娠第 12-15 天，通过灌胃用玉米油载体或 2.5mg/kg 或 5mg/kg 的 CPF 处理怀孕的老鼠。在成年期进行社会偏好、社会和非社会条件性位置偏好任务测试。通过 qPCR 测量下丘脑催产素转录本的表达。
氯菊酯（妊娠第 12-15 天 5mg/kg）以剂量和性别依赖的方式减少了对同种异体的先天偏好。在妊娠第 12-15 天暴露于 5mg/kg CPF 的雄性成年小鼠表现出社会偏好降低。母体接受任何剂量 CPF 处理的后代的社会条件性位置偏好受损。母体暴露于 2.5mg/kg 但不暴露于 5mg/kg 氯菊酯的后代的非社会奖赏性位置条件形成受损。产前氯菊酯处理并没有改变下丘脑催产素 mRNA 的表达，尽管在雌性中表达显著降低。
产前氯菊酯以性别依赖的方式在成年小鼠中诱导先天和习得的社会缺陷和非特异性调节缺陷。雄性在更高剂量下表现出特定的社会缺陷，而雄性和雌性在中等剂量下表现出更普遍的调节缺陷。
