Effect of dibutyltin on placental and fetal toxicity in rat

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...

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Published in:Journal of toxicological sciences 2017/12/01, Vol.42(6), pp.741-753
Main Authors: Furukawa, Satoshi, Tsuji, Naho, Kobayashi, Yoshiyuki, Yamagishi, Yoshikazu, Hayashi, Seigo, Abe, Masayoshi, Kuroda, Yusuke, Kimura, Masayuki, Hayakawa, Chisato, Sugiyama, Akihiko
Format: Article
Language:eng ; jpn
Subjects:
Administration, Oral
Allantois
Animals
Apoptosis
Apoptosis - drug effects
Craniofacial syndromes
Decidua
Dibutyltin
Dichlorides
Embryos
Facial Bones - abnormalities
Facial Bones - embryology
Female
Fetal Growth Retardation - chemically induced
Fetal Mortality
Fetal resorption
Fetal Weight - drug effects
Fetuses
Gestation
Gestational Age
Growth rate
Hypoplasia
Inductively coupled plasma mass spectrometry
LA-ICP-MS
Laser ablation
Lesions
Male
Malformation
Mass spectrometry
Mass spectroscopy
Maternal-Fetal Exchange - drug effects
Oral administration
Organ Size - drug effects
Organotin Compounds - administration & dosage
Organotin Compounds - pharmacokinetics
Organotin Compounds - toxicity
Placenta
Placenta - anatomy & histology
Placenta - drug effects
Placenta - metabolism
Pregnancy
Rat
Rats, Wistar
Skull - abnormalities
Skull - embryology
Tin
Tissue Distribution
Toxicity
Weight
Yolk
Yolk sac
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Summary: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.
ISSN:0388-1350
1880-3989
DOI:10.2131/jts.42.741