Cilley R E, Zgleszewski S E, Krummel T M, Chinoy M R
Department of Surgery, The Pennsylvania State University College of Medicine, Milton S. Hershey Medical Center, Hershey 17033, USA.
Am J Physiol. 1997 Feb;272(2 Pt 1):L362-71. doi: 10.1152/ajplung.1997.272.2.L362.
2,4-Dichlorophenyl-p-nitrophenyl ether (nitrofen) is known to induce pulmonary hypoplasia (PH) with or without diaphragmatic hernias (DH) in rats and mice. We determined the timing of administration and dose of nitrofen needed to create left-sided DH and PH in fetal mice. Time-dated pregnant CD-1 mice were gavaged with various doses of nitrofen in the later one-half of gestational days (GD) 8-11. Fetuses were removed by laparotomy at GD 14, fixed, and evaluated histologically. Fetal lung size was inversely related to nitrofen dose. Morphometric analysis of normal and nitrofen-exposed hypoplastic lungs at the pseudoglandular stage revealed significant differences in lung length, surface area, and in the number of airways. Left-sided DH were observed in a "dorsolateral" position accompanied by PH in approximately 30% of GD 14 fetuses exposed to 25 mg nitrofen on GD 8. A minimal portion of liver was present in the hernia. The lungs of fetuses exposed on GD 9, 10, and 11 progressed to near normal size. Murine fetuses exposed to 25 mg nitrofen on GD 8 resulted in PH and DH, whereas other doses created dose-dependent PH alone or none at all on GD 11. Our study established that, to create left-sided DH and PH in murine fetuses, nitrofen dose specificity and time of administration during gestation were crucial.
已知2,4-二氯苯基对硝基苯醚（除草醚）可在大鼠和小鼠中诱发肺发育不全（PH），伴或不伴有膈疝（DH）。我们确定了在胎鼠中造成左侧DH和PH所需的除草醚给药时间和剂量。对怀孕时间确定的CD-1小鼠在妊娠第8至11天的后半期给予不同剂量的除草醚灌胃。在妊娠第14天通过剖腹术取出胎儿，固定后进行组织学评估。胎儿肺大小与除草醚剂量呈负相关。对假腺期正常和除草醚暴露诱导的发育不全肺进行形态计量分析，发现肺长度、表面积和气道数量存在显著差异。在妊娠第8天暴露于25 mg除草醚的约30%妊娠第14天胎儿中，观察到左侧DH处于“背外侧”位置并伴有PH。疝内有一小部分肝脏。在妊娠第9、10和11天暴露的胎儿肺发育至接近正常大小。妊娠第8天暴露于25 mg除草醚的鼠胎儿出现PH和DH，而其他剂量在妊娠第11天单独产生剂量依赖性PH或根本不产生。我们的研究表明，要在鼠胎儿中造成左侧DH和PH，除草醚剂量特异性和妊娠期给药时间至关重要。
