Abstract：
Phenytoin, an antiepileptic drug, induces neurotoxicity and abnormal embryonic development and reduces spontaneous locomotor activity in fish. However, its effects on other endpoints remain unclear. Therefore, we investigated the effects of phenytoin on the swimming behavior and reproductive ability of Japanese medaka. Abnormalities in swimming behavior, such as imbalance, rotation, rollover, and vertical swimming, were observed. However, when phenytoin exposure was discontinued, the behavioral abnormality rates decreased. Phenytoin exposure also significantly reduced reproductive ability. By investigating reproduction-related gene expression of gnrh1, gnrh2, fshb, and lhb remained unchanged in males and females. In contrast, kiss1 expression was significantly suppressed due to phenytoin exposure in males and females. kiss2 expression was also significantly suppressed in females but not in males. We filmed videos to examine phenytoin exposure effects on sexual behavior. Females showed no interest in the male\'s courtship. As the kisspeptin 1 system controls sexual behavior in Japanese medaka, phenytoin exposure may have decreased kiss1 expression, which decreased female reproductive motivation; hence, they did not spawn eggs. This is the first study to show that phenytoin exposure induces behavioral abnormalities, and suppresses kiss1 expression and reproductive performance in Japanese medaka.
摘要：
苯妥英,一种抗癫痫药,诱导神经毒性和异常的胚胎发育，并降低鱼类的自发运动活动。然而,其对其他终点的影响尚不清楚.因此,我们研究了苯妥英钠对日本medaka游泳行为和生殖能力的影响。游泳行为异常,比如不平衡，旋转,展期,垂直游泳，被观察到。然而,当苯妥英钠接触停止时，行为异常率下降。苯妥英暴露也显著降低了生殖能力。通过研究gnrh1，gnrh2，fshb的繁殖相关基因表达，lhb在男性和女性中保持不变。相比之下,由于苯妥英钠在男性和女性中的暴露，kiss1表达被显着抑制。kiss2的表达在女性中也被显著抑制，而在男性中没有。我们拍摄了视频来检查苯妥英钠暴露对性行为的影响。女性对男性的求爱没有兴趣。由于kisspeptin1系统在日本平准花中控制性行为，苯妥英暴露可能会降低KISS1表达，这降低了女性生殖动机；因此，他们没有产卵。这是第一项研究表明苯妥英暴露会导致行为异常，并抑制日本青a的kiss1表达和生殖表现。
