Furukawa Satoshi, Tsuji Naho, Kobayashi Yoshiyuki, Yamagishi Yoshikazu, Hayashi Seigo, Abe Masayoshi, Kuroda Yusuke, Kimura Masayuki, Hayakawa Chisato, Sugiyama Akihiko
Biological Research Laboratories, Nissan Chemical Industries, Ltd.
Chemical Research Laboratories, Nissan Chemical Industries, Ltd.
J Toxicol Sci. 2017;42(6):741-753. doi: 10.2131/jts.42.741.
In order to elucidate the effect of chorioallantoic and yolk sac placenta on the embryonic/fetal toxicity in dibutyltin dichloride (DBTCl)-exposed rats, we examined the histopathological changes and the tissue distribution of dibutyltin in the placentas and embryos. DBTCl was orally administered to the groups at doses of 0 mg/kg during gestation days (GD)s 7-9 (control group) and 20 mg/kg during GDs 7-9 (GD7-9 treated group), and GDs 10-12 (GD10-12 treated group). The total fetal mortality was increased, and malformations characterized by craniofacial dysmorphism were detected in the GD7-9 treated group. The embryonic/fetal weight and placental weight showed a decrease in both DBTCl-treated groups. Histologically, some embryos on GD 9.5 in the GD7-9 treated group underwent apoptosis without any changes of yolk sac. In the laser ablation-inductively coupled plasma-mass spectrometry analysis (LA-ICP-MS), tin was detected in the embryo, allantois, yolk sac, ectoplacental cone and decidual mass surrounding the conceptus on GD 9.5 in the GD7-9 treated group. Thus, it is considered that the embryo in this period is specifically sensitive to DBTCl-induced apoptosis, compared with other parts. The chorioallantoic placentas in both DBTCl-treated groups showed the developmental delay and hypoplasia in the fetal parts of placenta, resulting from apoptosis and mitotic inhibition. Thus, it was speculated that the DBTCl-induced malformations and fetal resorption resulted from the apoptosis in the embryo caused by the direct effect of DBTCl. The DBTCl-induced lesions in the chorioallantoic placenta were a non-specific transient developmental retardation in the fetal parts of placenta, leading to intrauterine growth retardation.
为了阐明绒膜尿囊胎盘和卵黄囊胎盘对二氯化二丁基锡（DBTCl）暴露大鼠胚胎/胎儿毒性的影响，我们检查了胎盘和胚胎的组织病理学变化以及二丁基锡在其中的组织分布。在妊娠第7至9天，给对照组大鼠口服剂量为0 mg/kg的DBTCl；给第7至9天处理组大鼠口服剂量为20 mg/kg的DBTCl；给第10至12天处理组大鼠在妊娠第10至12天口服剂量为20 mg/kg的DBTCl。第7至9天处理组的总胎儿死亡率增加，并且检测到以颅面畸形为特征的畸形。两个DBTCl处理组的胚胎/胎儿体重和胎盘重量均下降。组织学上，第7至9天处理组中妊娠第9.5天的一些胚胎发生凋亡，而卵黄囊无任何变化。在激光烧蚀-电感耦合等离子体质谱分析（LA-ICP-MS）中，在第7至9天处理组妊娠第9.5天的胚胎、尿囊、卵黄囊、外胎盘锥体和围绕孕体的蜕膜团中检测到锡。因此，与其他部位相比，这个时期的胚胎被认为对DBTCl诱导的凋亡特别敏感。两个DBTCl处理组的绒膜尿囊胎盘均显示胎盘胎儿部分发育延迟和发育不全，这是由凋亡和有丝分裂抑制引起的。因此，推测DBTCl诱导的畸形和胎儿吸收是由DBTCl的直接作用导致胚胎凋亡引起的。DBTCl诱导的绒膜尿囊胎盘病变是胎盘胎儿部分非特异性的短暂发育迟缓，导致宫内生长迟缓。
