Abstract：
BACKGROUND: Aripiprazole (ARI) is a recently developed antipsychotic medication that belongs to the second generation of antipsychotics. The literature has contradictory information regarding ARI, which has been classified as pregnant use category C by the FDA.
METHODS: 125 pathogen-free fertilized eggs were incubated for 28 h and divided into five groups of 25 eggs each (including the control group), and 18 eggs with intact integrity were selected from each group. After the experimental groups were divided, ARI was administered subblastodermally with a Hamilton micro-injector at 4 different doses (1 mg/kg, 5 mg/kg, 10 mg/kg, 20 mg/kg). At the 48th hour of incubation, all eggs were hatched and embryos were removed from the embryonic membranes. And then morphologic (position of the neural tube (open or closed), crown-rump length, number of somites, embryological development status), histopathologic (apoptosis (caspase 3), cell proliferation (PCNA), in situ recognition of DNA breaks (tunnel)), genetic (BRE gene expression) analyzes were performed.
RESULTS: According to the results of the morphological analysis, when the frequency of neural tube patency was evaluated among the experimental groups, a statistically significant difference was determined between the control group and all groups (p < 0.001). In addition, the mean crown-rump length and somite number of the embryos decreased in a dose-dependent manner compared to the control group. It was determined that mRNA levels of the BRE gene decreased in embryos exposed to ARI compared to the control group (p < 0.001).
CONCLUSIONS: Morphologically, histopathologically, and genetically, aripiprazole exposure delayed neurogenesis and development in early chick embryos. These findings suggest its use in pregnant women may be teratogenic. We note that these results are preliminary for pregnant women, but they should be expanded and studied with additional and other samples.
METHODS: 125 pathogen-free fertilized eggs were incubated for 28 h and divided into five groups of 25 eggs each (including the control group), and 18 eggs with intact integrity were selected from each group. After the experimental groups were divided, ARI was administered subblastodermally with a Hamilton micro-injector at 4 different doses (1 mg/kg, 5 mg/kg, 10 mg/kg, 20 mg/kg). At the 48th hour of incubation, all eggs were hatched and embryos were removed from the embryonic membranes. And then morphologic (position of the neural tube (open or closed), crown-rump length, number of somites, embryological development status), histopathologic (apoptosis (caspase 3), cell proliferation (PCNA), in situ recognition of DNA breaks (tunnel)), genetic (BRE gene expression) analyzes were performed.
RESULTS: According to the results of the morphological analysis, when the frequency of neural tube patency was evaluated among the experimental groups, a statistically significant difference was determined between the control group and all groups (p < 0.001). In addition, the mean crown-rump length and somite number of the embryos decreased in a dose-dependent manner compared to the control group. It was determined that mRNA levels of the BRE gene decreased in embryos exposed to ARI compared to the control group (p < 0.001).
CONCLUSIONS: Morphologically, histopathologically, and genetically, aripiprazole exposure delayed neurogenesis and development in early chick embryos. These findings suggest its use in pregnant women may be teratogenic. We note that these results are preliminary for pregnant women, but they should be expanded and studied with additional and other samples.
摘要：
背景：阿立哌唑（ARI）是最近开发的抗精神病药物，属于第二代抗精神病药。文献中关于ARI的信息相互矛盾，被FDA列为怀孕使用C类。
方法：将125个无病原体受精卵孵育28h，分为五组，每组25个卵（包括对照组），每组18个完整的卵。在实验分组后,ARI在4种不同剂量（1mg/kg，5mg/kg,10mg/kg,20mg/kg)。在孵化的第48小时，所有卵都孵化，胚胎从胚膜中取出。然后形态学（神经管的位置（打开或关闭），皇冠臀部长度，somites的数量，胚胎发育状态），组织病理学（凋亡（caspase3），细胞增殖（PCNA），DNA断裂的原位识别（隧道）），进行遗传(BRE基因表达)分析。
结果：根据形态学分析的结果，当在实验组中评估神经管通畅的频率时，对照组与所有组之间的统计学差异显著(p<0.001).此外,与对照组相比，胚胎的平均冠部长度和体节数以剂量依赖性方式减少。确定与对照组相比,暴露于ARI的胚胎中BRE基因的mRNA水平降低(p<0.001)。
结论：形态学，组织病理学,和基因，阿立哌唑暴露可延迟早期鸡胚的神经发生和发育。这些发现表明其在孕妇中的使用可能是致畸的。我们注意到，这些结果是孕妇的初步结果，但他们应该扩大和研究与额外的和其他样品。
方法：将125个无病原体受精卵孵育28h，分为五组，每组25个卵（包括对照组），每组18个完整的卵。在实验分组后,ARI在4种不同剂量（1mg/kg，5mg/kg,10mg/kg,20mg/kg)。在孵化的第48小时，所有卵都孵化，胚胎从胚膜中取出。然后形态学（神经管的位置（打开或关闭），皇冠臀部长度，somites的数量，胚胎发育状态），组织病理学（凋亡（caspase3），细胞增殖（PCNA），DNA断裂的原位识别（隧道）），进行遗传(BRE基因表达)分析。
结果：根据形态学分析的结果，当在实验组中评估神经管通畅的频率时，对照组与所有组之间的统计学差异显著(p<0.001).此外,与对照组相比，胚胎的平均冠部长度和体节数以剂量依赖性方式减少。确定与对照组相比,暴露于ARI的胚胎中BRE基因的mRNA水平降低(p<0.001)。
结论：形态学，组织病理学,和基因，阿立哌唑暴露可延迟早期鸡胚的神经发生和发育。这些发现表明其在孕妇中的使用可能是致畸的。我们注意到，这些结果是孕妇的初步结果，但他们应该扩大和研究与额外的和其他样品。
