official journal of Congeital Anomalies Research Association of Japan
Online ISSN : 2433-1503
Print ISSN : 0037-2285
Volume 48 , Issue 2
Congenital Anomalies
Showing 1-10 articles out of 10 articles from the selected issue
  • 2008 Volume 48 Issue 2 Pages J1
    Published: 2008
    Released: August 12, 2021
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  • 2008 Volume 48 Issue 2 Pages 57-62
    Published: 2008
    Released: August 12, 2021
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    ABSTRACT  Biotin is a water-soluble vitamin which functions as a coenzyme of carboxylases in glucose and amino acid metabolism and fatty acid synthesis. Biotin is also essential for maintaining reproductive function. Biotin deficiency during gestation induces cleft palate, micrognathia and limb hypoplasia in mouse fetuses at near term. Maternal biotin deficiency is severely tetatogenic in mammals. However, the relationship between abnormal morphogenesis and biotin deficiency is not sufficiently clear. This study was conducted to elucidate the mechanism of biotin transport from dams to embryos and the nutritional roles of biotin in ICR mice. Pregnant mice were given either a biotin-deficient or biotin-supplemented diet, and biotin and biotinidase activity were determined in dams and fetuses. It became evident that biotin was supplied from dams to growing embryos during morphogenesis. In particular, a large amount of biotin was transported to palates and mandibles on days 12–15 of gestation. The transportation of biotin to fetuses differed among fetal growth periods and organs. These results suggest that biotin is an essential nutrient and may play an important role in embryonic growth.
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  • 2008 Volume 48 Issue 2 Pages 63-67
    Published: 2008
    Released: August 12, 2021
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    ABSTRACT  Androgen plays a crucial role in initiating and maintaining the expression of male sexual characteristics in mammals. In humans and mice, any defects along the pathway of androgen functions result in congenital urogenital abnormalities. The genital tubercle (GT), an anlage of the external genitalia, differentiates into a penis in males and a clitoris in females. Although masculinization of the external genitalia is androgen-dependent, the molecular pathway of its potential downstream genes is largely unclear. To identify the genes involved in mouse GT masculinization, we performed gene expression analyses, such as real-time quantitative polymerase chain reaction and section in situ hybridization analysis. From our studies we have identified candidate genes, Cyp1b1, Fkbp51 and MafB as potential androgen targets during mouse GT masculinization.
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  • 2008 Volume 48 Issue 2 Pages 68-73
    Published: 2008
    Released: August 12, 2021
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    ABSTRACT  Morphological and immunohistological examinations were performed to reveal the mechanisms of cleft palate induction by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). ICR strain mice 8–10 weeks of age were used in the study. TCDD was administered in olive oil on gestation day (GD) 12.5 with gastric tubes at 40 μg/kg. From GD 13.5 to 16.5, palates were examined by scanning electron microscopy (SEM), hematoxyline–eosin (HE) staining, and immunohistochemical staining of FGFR1/2, TGF-β3, MSX1 and LHX8. In the control group, both of the palatal shelves began elevating on GD 14.0 and finished within 6 h. After the elevation, all of the shelves had completely fused with each other on GD 14.5. In the TCDD-treated group, palatal shelves elevated 1 day later than in the control group. However, all palates had elevated by GD 15.0. After the elevation, the shelves contacted each other and fused; however, they were separated on GD16.0. HE staining showed that medial edge epithelium (MEE) was thinner in the TCDD group than in the control group. MEE observed under a high magnification (×2500) exhibited filopodia-like filaments and the cells were bulged in the control group. In contrast, in the TCDD group, no filaments were observed and the cells were flat with unclear boundaries. Immunohistologically, there were no characteristic findings except for FGFR1. FGFR1 was not expressed in the TCDD group after the fusion phase (GD 14.5). TCDD induces many morphological and molecular changes to MEE cells and causes cleft palates.
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  • 2008 Volume 48 Issue 2 Pages 74-80
    Published: 2008
    Released: August 12, 2021
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    ABSTRACT  The responsible gene of genetic polydactyly/arhinencephaly mouse (Pdn/Pdn) is Gli3. Pdn/Pdn exhibits absence of the olfactory bulb, suggesting telencephalic dysmorphogenesis. It has been cleared that a transposon was inserted into intron 3 of the Gli3 gene in the Pdn mouse. Adequate PCR primers in the intron 3 and transposon allowed us to discriminate +/+, Pdn/+ and Pdn/Pdn embryos. After genotyping of the Pdn embryos using genomic DNA from the yolk sac membrane, gene expressions in the embryo proper were analyzed by DNA microarray, real-time PCR and whole-mount in situ hybridization (WISH) methods. DNA microarray detected 368 depressed and 425 over-expressed genes in the Pdn/Pdn mouse embryos on day 9 of gestation. In these genes, six signaling pathway and 20 transcription factor genes were included. From these genes, we further investigated Gli3, Emx2, Wnt8b and Wnt7b gene expressions using real-time PCR and WISH, and depression of these gene expression amounts and altered expression patterns were confirmed. Although alterations of Shh and Fgf8 gene expressions were not detected in the DNA microarray, as these genes have been closed up in the telencephalic morphogenesis, we investigated these gene expressions by real-time PCR and WISH. Shh gene expression amount and pattern were not changed. Alteration of Fgf8 gene expression amount was not detected also in the real-time PCR, but altered expression pattern was detected in the Pdn/Pdn embryos by WISH. From the present data, we suggested that Emx2, Wnt8b, Wnt7b and Fgf8 are the important Gli3 signaling pathway in the morphogenesis of telencephalon.
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  • 2008 Volume 48 Issue 2 Pages 81-86
    Published: 2008
    Released: August 12, 2021
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    ABSTRACT  Adrenocorticotropic hormone (ACTH) has been suggested to have possible roles in the fetal testes, one of the organs that express its specific receptors, melanocortin type 2 and 5 receptors (MC2R and MC5R), during the fetal period. We investigated the effect of ACTH on the cells in the testis cord of the fetal mouse testis by inducing ACTH-secreting AtT20 tumor cells in mouse fetuses. We first identified that mouse testicular germ cells at embryonic day (E) 16.5 and E18.5 spermatogonia were entirely CDH1 (E-cadherin)-positive by immunohistochemistry. We next performed AtT20-cell transplantation into the mouse fetus at E12.5, and analyzed ACTH effects on the development of fetal male mouse germ cells that express MC2R and MC5R at E16.5 and E18.5. The spermatogonia in the testis of AtT20-implanted embryos exhibited morphological changes, including pyknotic nuclei and swollen cytoplasm. In the AtT20-implanted embryos, the number of spermatogonia per unit area of the testis cord was significantly lower, but there were more pyknotic spermatogonia than in the controls. Single-stranded DNA-positive (apoptotic) and histone H3-positive (mitotic) spermatogonia were rarely observed and their numbers did not significantly differ in the two groups. Anti-Müllerian hormone (AMH)-positive Sertoli cells, another cell type that constitutes the fetal testis cord but does not express MC2R or MC5R, showed no apparent morphological changes compared with controls, nor were their numbers in the two groups significantly different between the two groups. These results suggest that ACTH, via MC2R and/or MC5R, may be involved in the nonapoptotic cell death of fetal mouse spermatogonia that is observed during the normal perinatal period.
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  • 2008 Volume 48 Issue 2 Pages 87-91
    Published: 2008
    Released: August 12, 2021
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    ABSTRACT  There is limited information on the specific structural birth defects associated with the abdominal wall defects (AWD) omphalocele and gastroschisis, particularly which defects occur with the AWD at greater than expected rates (rates among all infants and fetuses with birth defects other than the AWD). Using data from a population-based birth defects registry in Hawaii, this study calculated the rates for 48 specific structural birth defects among the AWD and compared these rates to the expected rates. There were 60 cases of omphalocele, 96 cases of gastroschisis, and 12 161 infants and fetuses with structural birth defects excluding the AWD among deliveries during 1986–2001. For omphalocele, higher than expected rates were found for 23 (47.9%) of the defects. These involved defects of a variety of organ systems. For gastroschisis, higher than expected rates were found for 8 (16.7%) of the defects, mainly neural tube defects (NTD) and specific defects of the orofacial and gastrointestinal system and the genital and urinary system. Both omphalocele and gastroschisis had elevated rates for NTD, intestinal atresia/stenosis, malrotation of intestines, obstructive genitourinary defects and limb reduction deformities. Certain specific structural birth defects occurred more often than expected with the AWD. The associated birth defects tended to vary between omphalocele and gastroschisis, although there were a few similarities. Due to the small number of cases, further research involving larger amounts of data are warranted.
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  • 2008 Volume 48 Issue 2 Pages 92-96
    Published: 2008
    Released: August 12, 2021
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    ABSTRACT  Antenatal sonographic diagnosis of twin–twin transfusion syndrome (TTTS) is based on findings of a twin oligo-polyhydramnios sequence (TOPS) observed in monochorionic twin fetuses. However, TTTS can develop without a significant characteristic intertwin discordance in the amniotic fluid volumes. We report an uncommon form of TTTS without TOPS showing severe anemia in one twin and polycythemia in the other. Based on sonographic findings, it is considered that the recipient twin became the donor later in gestation, and vice versa. It is concluded therefore that even in the absence of TOPS, the possibility of severe TTTS with a suspected reversal of donor-recipient phenotypes during pregnancy should not be excluded, and serial Doppler studies including the measurement of the middle cerebral artery peak systolic velocity should be routinely performed even in seemingly uncomplicated monochorionic twin fetuses without TOPS.
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  • 2008 Volume 48 Issue 2 Pages 97-100
    Published: 2008
    Released: August 12, 2021
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  • 2008 Volume 48 Issue 2 Pages 101
    Published: 2008
    Released: August 12, 2021
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