ABSTRACT Developmental toxicity following administration of dibutyl phthalate (DBF) and its major metabolite, monobutyl phthalate (MBuP), by gavage was determined in Wistar rats. DBF on days 0–8 of pregnancy induced an increase in the incidence of preimplantation loss at 1250 mg/kg and higher and postimplantation loss at 750 mg/kg and higher. MBuP on days 0–8 of pregnancy produced an increase in the incidence of pre-and postimplantation loss at 1000 mg/kg. DBF on days 7–15 of pregnancy caused an increase in the incidence of fetuses with malformations at 750 mg/kg. MBuP on days 7–15 of pregnancy produced an increased incidence of fetuses with malformations at 500 mg/kg and higher. DBF on days 15–17 of pregnancy resulted in a decrease in the anogenital distance (AGD) of male fetuses and increase in the incidence of fetuses with undescended testes at 500 mg/kg and higher. MBuP on days 15–17 of pregnancy caused a decreased male AGD and increased incidence of fetuses with undescended testes at 250 mg/kg and higher. No effect of DBF and MBuP on the AGD was found in female offspring. The spectrum of fetal malformations, dependence of gestational days of treatment on the manifestation of teratogenicity, and alterations in development of the male reproductive system observed after administration of DBF were in good agreement with those observed after administration of MBuP. These findings suggest that MBuP may be responsible for the induction of developmental toxic effects of DBP. The doses that produced a decrease in the AGD and undescended testes in male offspring were lower than those producing maternal toxicity, fetal malformations after administration during major organogenesis, and embryonic loss. The male reproductive system may be more susceptible than other organ systems to DBP and MBuP toxicity after maternal exposure.
ABSTRACT So far, 46 cases of placental mesenchymal dysplasia have been reported worldwide. We encountered 15 cases of placental mesenchymal dysplasia (PMD) including 7 cases delivered in our hospital. The incidence of PMD in our hospital was therefore, 7/30, 758 (0.02%). The PMD had a peculiar appearance. In the gross findings, large placenta with intestine-like dilatation of the vessels on the fetal side was reported. Microscopically, cistern-like dilatation of the stem villi, fetal artery thrombosis, and villous hemorrhage were reported. However, we believe most of these findings are secondary rather than the primary of mesenchymal dysplasia. Therefore, we investigated 15 other cases of mesenchymal dysplasia, and found including vascular abnormality of the stem, intermediate and terminal villi in all case of PMD. The abnormality was observed in the vessels of the periphery of the stem villi and their vessel walls were thin and appeared weak. The intermediate villous vessels were unusual, tangled. The terminal villous abnormalities showed chorangiosis and stromal hyperplasia. These findings are mesenchymal dysplasia origin. Moreover, PMD showed female-predominant. 14/15 was female among our cases, We discuss the relationship between mesenchymal dysplasia and the X chromosome in this paper.
ABSTRACT The phenotype of the genetic polydactyly/arhinencephaly mouse (Pdn/Pdn) is similar to Greig cephalopolysyndactyly syndrome (GCPS), whose responsible gene is GLI3. Suppression of Gli3 gene expression has been observed in the Pdn/Pdn and integration of retrotransposon in Gli3 gene in the Pdn mouse has been reported. Thus, the responsible gene for Pdn/Pdn is thought to be Gli3, but the site of mutation within the gene has not been demarcated.
In the present study, we demonstrated that 5442 bp of early retrotransposon was inserted into intron 3 of Gli3 gene in the Pdn mouse (Gli3Pdn). This transposon had almost the same sequence as MMY17106 (EMBL). It had 317-bp long terminal repeat at both ends followed by the identical 6-bp target duplication sequence, GAGACT. Forward and reverse PCR primers were constructed in intron 3 near the insertion point, and a forward primer in the transposon was also constructed. These primers allowed us to discriminate +/+, Pdn/+ and Pdn/Pdn embryos by the PCR products. Morphological determination of the genotypes in the Pdn mouse embryos is impossible before day 12 of gestation. Quick discrimination method of genotypes developed in the present study allows us to investigate the early dysmorphogenetic mechanisms in the brain and limbs in the Pdn/Pdn embryos. Then, the dysmorphogenetic mechanisms in the Pdn/Pdn may be extrapolated to those in GCPS.
ABSTRACT Dioxins are one of the accumulative endocrine disruptors that are detected from the human body. They are known to induce a wide range of adverse effects, however there are only a few methods that have been reported to reduce them. Consequently, a new effective method to reduce the dioxins in our body needs to be developed. To develop such a method, animal models are needed to be experimented on in order to evaluate each method required. In this study, an animal model using guinea pigs was made to evaluate the methods. Three weeks after the administration of 0.05 μg/kg/day of TCDD for 5 days, the serum TCDD level in the guinea pigs was almost equal to the relatively high dioxin level among human serum. Our present study suggests that the guinea pig model used in this research can be effective for further study in the method to reduce accumulated dioxins in the body.
ABSTRACT PD strain male rats that carry an autosomal recessive gene, preaxial duplication (gene symbol: pd), are sterile in the homozygous condition (pd/pd) due to a spermatogenic breakdown in the process of spermatogenesis at the spermatocyte and/or spermatid stage(s), although heterozygotes (pd/+) are normal. In this study, pd/pd males were examined for the presence of abnormal association of the sex chromosomes that might lead to spermatogenic breakdown. Light and electron microscopic observations of the chromosomes at meiotic prophase and metaphase in primary spermatocytes revealed several types of abnormal X-Y association and configurations in pd/pd males. However, the incidences of the abnormal configuration were comparable to those in pd/+ males. These results suggest that abnormal X-Y chromosome association in the germ cells is not a significant cause of spermatogenic breakdown in pd/pd males.