Ellis W G, De Roos F, Kavlock R J, Zeman F J
Department of Pathology, University of California, Davis 95616.
Teratog Carcinog Mutagen. 1988;8(6):377-91. doi: 10.1002/tcm.1770080607.
Benomyl, a benzimidazole fungicide, was administered by gavage to pregnant Sprague-Dawley rats in a daily dose of 62.5 mg/kg of maternal body weight beginning at gestational day (GD) 7. Fetuses examined histologically at GD16 or GD20 revealed a high incidence of craniocerebral anomalies--82.6% of those examined at GD16 and 100% of those examined at GD20. Hydrocephalus occurred in 65.2% of fetuses examined at GD16 and in 58.8% at GD20 but was more severe in the GD20 fetuses. A second common anomaly, termed periventricular "overgrowth" (PVO), consisted of subependymal cell masses that in some fetuses obliterated normal subcortical structures. PVO occurred in 34.8% of fetuses examined at GD16 and 76.5% at GD20. The size of the subependymal masses and the regions involved were considerably greater in the GD20 than the GD16 fetuses. Less common anomalies in the GD20 fetuses were periventricular necrosis (41.2%), a single fetus with exencephaly and another with porencephaly. In the majority of malformed fetuses, the severity of hydrocephalus did not parallel the severity of PVO around the lateral and third ventricles. PVO involved tissues surrounding the cerebral aqueduct in 17.4% of GD16 fetuses and 38.2% of GD20 fetuses. This "overgrowth" distorted the cerebral aqueduct in a large number of fetuses with ventriculomegaly, and at GD20 moderate and severe ventriculomegaly was in every instance associated with a narrow or completely occluded cerebral aqueduct. These relationships suggest that PVO in the midbrain may play a role in the production of aqueductal stenosis and hydrocephalus in this experimental model.
苯菌灵是一种苯并咪唑类杀菌剂，从妊娠第7天开始，以每日62.5毫克/千克母体体重的剂量经口灌胃给予怀孕的斯普拉格-道利大鼠。在妊娠第16天或第20天进行组织学检查的胎儿显示，颅脑异常的发生率很高——在妊娠第16天检查的胎儿中发生率为82.6%，在妊娠第20天检查的胎儿中为100%。在妊娠第16天检查的胎儿中，脑积水发生率为65.2%，在妊娠第20天为58.8%，但在妊娠第20天的胎儿中更为严重。另一种常见的异常称为脑室周围“过度生长”（PVO），由室管膜下细胞团组成，在一些胎儿中这些细胞团会破坏正常的皮质下结构。在妊娠第16天检查的胎儿中，PVO发生率为34.8%，在妊娠第20天为76.5%。与妊娠第16天的胎儿相比，妊娠第20天胎儿的室管膜下肿块大小和受累区域明显更大。妊娠第20天胎儿中较少见的异常是脑室周围坏死（41.2%），有1例无脑儿和1例脑穿通畸形胎儿。在大多数畸形胎儿中，脑积水的严重程度与侧脑室和第三脑室周围PVO的严重程度并不平行。在妊娠第16天的胎儿中，17.4%的胎儿PVO累及中脑导水管周围组织，在妊娠第20天的胎儿中为38.2%。这种“过度生长”在大量脑室扩大的胎儿中使中脑导水管变形，在妊娠第20天，中度和重度脑室扩大的每一例均伴有中脑导水管狭窄或完全闭塞。这些关系表明，在这个实验模型中，中脑的PVO可能在导水管狭窄和脑积水的发生中起作用。
