The relationship between fetal growth restriction and small placenta in 6-mercaptopurine exposed rat

Furukawa, Satoshi; Hayashi, Seigo; Usuda, Koji; Abe, Masayoshi; Ogawa, Izumi

doi:10.1016/j.etp.2009.10.001

Cited by 16 publications

(16 citation statements)

References 24 publications

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“…The cell proliferative activity in the labyrinth zone is at its peak on GD 13 and then reduces toward late gestation (Furukawa et al, 2015). Therefore, the effect of these agents on the labyrinth zone is closely related to the proliferation period, and the developed lesions depend on the timing of treatment period, such as 6-mercaptopurine (Furukawa et al, 2011a) and cisplatin (Furukawa et al, 2013b). By contrast, chlorpromazine induces the nonspecific transient developmental retardation of placenta caused by apoptosis independently of the cell proliferation period (Furukawa et al, 2015).…”

Section: Discussionmentioning

confidence: 99%

Effect of dibutyltin on placental and fetal toxicity in rat

et al. 2017

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-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.

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Section: Discussionmentioning

confidence: 99%

Effect of dibutyltin on placental and fetal toxicity in rat

et al. 2017

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“…However, it has not been clear how the changes in placental size and function relate to changes in fetal metabolic demands 92 . The effect of placental size on IUGR was recently investigated in the placentas of rats exposed to 6-MP at various points of gestation 93 , as described below.…”

Section: Relationship Between Fetal Intrauterine Growth Restriction Amentioning

confidence: 99%

Toxicological Pathology in the Rat Placenta

et al. 2011

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The placenta grows rapidly for a short period with high blood flow during pregnancy and has multifaceted functions, such as its barrier function, nutritional transport, drug metabolizing activity and endocrine action. Consequently, the placenta is a highly susceptible target organ for drug- or chemical-induced adverse effects, and many placenta-toxic agents have been reported. However, histopathological examination of the placenta is not generally performed, and the placental toxicity index is only the placental weight change in rat reproductive toxicity studies. The placental cells originate from the trophectoderm of the embryo and the endometrium of the dam, proliferate and differentiate into a variety of tissues with interaction each other according to the development sequence, resulting in formation of a placenta. Therefore, drug- or chemical-induced placental lesions show various histopathological features depending on the toxicants and the exposure period, and the pathogenesis of placental toxicity is complicated. Placental weight assessment appears not to be enough to evaluate placental toxicity, and reproductive toxicity studies should pay more attention to histopathological evaluation of placental tissue. The detailed histopathological approaches to investigation of the pathogenesis of placental toxicity are considered to provide an important tool for understanding the mechanism of teratogenicity and developmental toxicity with embryo lethality, and could benefit reproductive toxicity studies.

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“…Particularly, the cell proliferative activity in the labyrinth zone is higher and keeps going for a longer period of time than that in other parts. After 6-mercaptopurine-treatment on GD 11, 13 or 15, the severity of labyrinth zone hypoplasia progressed in accord with the early time point of treatment, but the basal zone hypoplasia is induced by only the GD11-treatment (Furukawa et al, 2011a). With cisplatin, the metrial gland hypoplasia is induced by the treatment on GDs 11 and 12, but not on GDs 13 and 14 (Furukawa et al, 2013b).…”

Section: Discussionmentioning

confidence: 79%

“…The peak period of cell proliferation is different among each constitutive cell of the placenta, and each part/zone of the placenta has a specific sensitive period for toxicants. To support this, we previously reported that anti-cancer drug induced placental lesions were different among the treatment timings in 6-mercaptopurine (Furukawa et al, 2011a) and cisplatin (Furukawa et al, 2013b).…”

Section: Introductionmentioning

confidence: 73%

“…From these results, the chlorpromazine-induced IUGR had no relationship with the degree of placental weight loss. In addition, the degree of the placental weight reduction appeared to be within the range of adaptive reaction for the deterioration of placental function, by the results of the 6-mercaptopurine-or cisplatin-exposed placentas (Furukawa et al, 2011a(Furukawa et al, , 2013b. Thus, it was considered that the poor reproductive performance including fetal death was not only caused by a secondary effect on placental damage, but also by a direct effect of chlorpromazine on fetuses and/or a secondary effect on poor performance of dams.…”

Section: Discussionmentioning

confidence: 95%

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