■丙戊酸(VPA)是开发自闭症谱系障碍(ASD)临床前模型的最广泛使用的化学物质。然而,除了诱发自闭症,它会引起不同的致畸作用,比如牙齿畸形,尾巴扭结,后代的身体发育异常。到目前为止,没有研究探讨VPA引起的母亲行为不当,流产,和母性相食。我们旨在确定VPA在怀孕雌性Wistar大鼠中的同类相食作用以及VPA对引起流产频率的影响。
■我们的研究是在怀孕的Wistar大鼠上进行的。在妊娠日(GD)12.5,用溶解在250mg/mL浓度的盐水中的VPA(600mg/kg腹膜内)处理它们。观察结果是平均产仔数,平均雄性/雌性幼崽,平均死亡率,母性相食,平均活着的幼崽数量,畸形幼犬的自相残杀,流产,幼崽的生存分析,计算两个研究组(对照组和VPA治疗组)中观察到的死亡的比值和风险比.这项研究一直进行到断奶期。
■暴露于VPA的孕妇描绘了产仔数显着减少(P<0.0001),食人行为明显更高(P=0.0023),畸形幼崽的同类相食率显着高于对照组(P=0.0484)。VPA导致5名孕妇完全流产(流产)。此外,VPA组的死亡率百分比(P=0.0019)明显高于对照组。
■总的来说,VPA具有明显的致畸作用(后代的解剖学和形态学变化),并伴有母体行为破坏,导致Wistar雌性老鼠自相残杀。当前的手稿发现可以帮助调查VPA自闭症模型发展过程中母性行为破坏的新机制。
UNASSIGNED: Valproic acid (VPA) is the most widely used chemical to develop the preclinical model of autism spectrum disorder (ASD). However, in addition to inducing autism, it causes different teratogenic effects like teeth malformation, tail kink, and abnormal body growth in offspring. So far, no study has explored VPA-induced maternal misbehavior, miscarriage, and maternal
cannibalism. We aimed to determine the cannibalistic effects of VPA in pregnant female Wistar rats and VPA\'s influence on causing miscarriage frequency.
UNASSIGNED: Our study was conducted on pregnant Wistar rats. On gestation day (GD) 12.5, they were treated with VPA (600 mg/kg intraperitoneal) dissolved in saline at 250 mg/mL concentration. The observations were mean litter size, mean male/female pups, mean mortality, maternal
cannibalism, mean number of pups alive,
cannibalism of malformed pups, miscarriage, survival analysis of pups, and odds and risk ratio were calculated for deaths observed in both study (control and VPA-treated) groups. The study was conducted till the weaning period.
UNASSIGNED: VPA-exposed pregnant females portrayed significantly decreased litter size (P<0.0001), significantly higher cannibalistic behavior (P=0.0023), and significantly higher
cannibalism of malformed pups (P=0.0484) than the control group. VPA had caused complete pregnancy loss (miscarriage) in 5 pregnant females. Moreover, the VPA group\'s mortality percentage (P=0.0019) was significantly higher than the control group.
UNASSIGNED: Overall, VPA has marked teratogenic effects (anatomical and morphological changes in offspring) with maternal behavior disruption, which causes
cannibalism in Wistar female rats. The current manuscript findings can aid in investigating the novel mechanisms involved in maternal behavior disruption during the development of the VPA autism model.