Abstract：
Antipsychotic drugs (APDs) are used to treat many psychiatric illnesses as schizophrenia. Typical antipsychotic drugs (TAPDs) are being used; however, they have many side effects. Atypical antipsychotic drugs (AAPDs) are newer medications with known fewer side effects. Aripiprazole (ARI) is an AAPD, recommended by healthcare providers, even during pregnancy. It can cross the placental barrier and enter fetal circulation, so it might be possible that ARI can adversely impair normal placental development and growth, if it is given prenatally. ARI was applied orally to pregnant female rats in two doses (3& 6 mg/kg body weight). On gestation day 20, the mothers were sacrificed, and the placentas were removed and processed for general histological and electron microscopic evaluations. Immunohistochemistry was done using anti-PCNA (proliferating cell nuclear antigen), anti-Bax (for apoptosis) and anti-vascular endothelial growth factor alpha (VEGFA). Morphological evaluation revealed degenerative changes in the placenta as dark nuclei, vacuolization, and cyst formation. Ultra-structurally, there was degeneration of cellular components including organelles and nuclei. These changes were found in different cells of the basal and labyrinth zones and were dose dependent. Immunohistochemistry revealed upregulation of Bax and VEGFA and downregulation of PCNA. Prenatal administration of the AAPD, ARI to pregnant female rats resulted in histological changes in the placenta. Additionally, there was a decrease in cellular proliferation and increase in apoptosis, and vascular impairment. This indicates placental atrophy and dysgenesis and might suggest possible teratogenic effects to ARI, which needs further evaluation.
摘要：
抗精神病药物（APD）用于治疗精神分裂症等许多精神疾病。正在使用典型的抗精神病药物（TAPD）；然而，它们有很多副作用。非典型抗精神病药物（AAPD）是较新的药物，已知副作用较少。阿立哌唑（ARI）是一种AAPD，由医疗保健提供者推荐，即使在怀孕期间。它可以穿过胎盘屏障进入胎儿循环，因此，ARI可能会对正常的胎盘发育和生长产生不利影响，如果它是先期给予的。将ARI以两种剂量(3和6mg/kg体重)口服施用于怀孕的雌性大鼠。在妊娠第20天，母亲被牺牲了，并取出胎盘进行一般组织学和电子显微镜评估。使用抗PCNA（增殖细胞核抗原）进行免疫组织化学，抗Bax（用于凋亡）和抗血管内皮生长因子α（VEGFA）。形态学评估显示胎盘的退行性变化为暗核，真空化,和囊肿形成。超结构,包括细胞器和细胞核在内的细胞成分退化。这些变化在基底和迷宫区的不同细胞中发现，并且具有剂量依赖性。免疫组织化学显示Bax和VEGFA上调，PCNA下调。AAPD的产前管理，妊娠雌性大鼠的ARI导致胎盘的组织学改变。此外,细胞增殖减少，凋亡增加，和血管损伤。这表明胎盘萎缩和发育不全，并可能提示ARI可能的致畸作用，这需要进一步评估。
