Reproductive toxicology in animals with induced and spontaneous diabetes

Kalter, Harold

doi:10.1016/s0890-6238(96)00129-3

Cited by 25 publications

(17 citation statements)

References 102 publications

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“…The present study is concordant with past studies demonstrating embryopathy secondary to maternal diabetes in that a wide range of malformations was produced, and no single pattern of malformations specifically attributable to the maternal disease state was discernible (47). Among the most frequent single malformations was exencephaly, which is widely considered to be the murine equivalent of anencephaly (51), a congenital defect frequently found in human diabetic embryopathy (11).…”

Section: Discussionsupporting

confidence: 91%

“…Although several previous studies have demonstrated congenital malformations secondary to chemically induced maternal diabetes, in general, the correlation between the degree of maternal hyperglycemia and the rate or severity of teratogenesis has been poor (47). However, few if any studies of chemically induced diabetes have produced both the frequency of congenital defects and the extreme range of maternal glucose levels seen in the present investigation (47).…”

Section: Discussionmentioning

confidence: 51%

“…Another malformation consistently noted in studies of human diabetic embryopathy is spina bifida aperta (7,11). In animal models of maternal diabetes, however, spina bifida aperta has appeared very infrequently (47). The results of the present study demonstrate that heterozygosity for the murine Sp allele confers genetic susceptibility to spina bifida aperta produced by maternal ALX-induced diabetes.…”

Section: Discussionmentioning

confidence: 58%

“…Past studies of diabetic embryopathy in animal models have, as a group, been plagued with difficulties concerning differentiation between true congenital malformations versus developmental delay and between teratogenicity produced by the maternal diabetic condition versus direct effects of diabetogenic chemicals (47). Additionally, many studies introduce a potentially confounding variable by administering insulin to increase maternal survival and the rate of successful pregnancy.…”

Section: Discussionmentioning

confidence: 99%

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Diabetic Embryopathy in C57BL/6J Mice

et al. 2001

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Maternal diabetes (types 1 and 2) induces a broad array of congenital malformations, including neural tube defects (NTDs), in humans. One of the difficulties associated with studying diabetic embryopathy is the rarity of individual malformations. In an attempt to develop a sensitive animal model for maternal diabetes-induced NTDs, the present study uses chemically induced diabetes in an inbred mouse model with or without the splotch (Sp) mutation, a putatively nonfunctional allele of Pax3. Pax3 deficiency has been associated with an increase in NTDs. Female C57BL/6J mice, either with or without the Sp allele, were injected intravenously with alloxan (100 mg/kg), and plasma glucose was measured 3 days later. A wide range of hyperglycemia was induced, and these diabetic mice were bred to C57BL/6J males, some carrying the Sp allele. Gestational-day-18 fetuses were examined for developmental malformations. Fetuses from matings in which either parent carried the Sp allele were genotyped by polymerase chain reaction. Maternal diabetes significantly decreased fetal weight and increased the number of resorptions and malformations, including NTDs. A significant correlation was found between the level of maternal hyperglycemia and the malformation rate. The sex ratio for live fetuses in diabetic litters was significantly skewed toward male fetuses. Matings involving the Sp allele yielded litters with significantly higher percentages of maternal diabetes-induced spina bifida aperta but not exencephaly, and this increase was shown to be associated with the presence of a single copy of the Sp allele in affected fetuses. Thus, Pax3 haploinsufficiency in this murine model of diabetic embryopathy is associated with caudal but not cranial NTDs.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 51%

Section: Discussionmentioning

confidence: 58%

Section: Discussionmentioning

confidence: 99%

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Diabetic Embryopathy in C57BL/6J Mice

et al. 2001

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“…However, the contribution of these factors to the development of pregnancy complications has not been adequately explored in animal models. Comprehensive reviews of such models can be found in Kalter 44 and White and Jawerbaum 45 .…”

Section: Discussionmentioning

confidence: 99%

Estabelecimento de um modelo de gestação complicada por diabetes tipo 1 em camundongos: avaliação do seu impacto sobre o ambiente uterino no início da gestação.

Favaro¹

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AGRADECIMENTOSÀ minha querida Mãe, Vanda Favaro, muito obrigado pela sua constante preocupação com minha educação e minha vida. Você foi fundamental nessa caminhada. Ensinou-me valores que permeiam minha conduta, e incentivou-me a buscar um futuro melhor por meio da educação. Aos meus irmãos, Mishel Favaro Piveta e Renato Favaro, pelo companheirismo e apoio, vocês foram fundamentais! Aos meus avós Devair Favaro (in memorian) e Emilia Favaro (in memorian), pelo seu exemplo de dedicação à família. A família desempenha um papel essencial na construção da identidade do indivíduo, o suporte de vocês foi essencial para essa conquista. Espero que minha ausência seja compreendida.À Profa. Telma Zorn, minha "Mãe Científica", muito obrigado por me acolher em seu laboratório e em sua vida. Esses anos sob a sua orientação fizeram com que aumentasse ainda mais o amor que sinto pela universidade, educação e pesquisa. A Senhora é meu exemplo de educadora. Todo o conhecimento que me foi transmitido, pelas suas palavras e seu exemplo, constituem os alicerces que fundamentam minhas ações, como futuro pesquisador e educador.Aos integrantes do LBR & MEC, Ambart Covarrubias, amiga chilena e colaboradora; Cleusa Pelegrini, amiga e exemplo de dedicação, com quem tive a oportunidade de conviver e aprender muito sobre histologia, Fernanda Barrence, amiga e importante colaboradora, sua ajuda foi essencial para este estudo, assim como para o bom andamento do laboratório; Fernanda Fernandes, amiga, realizou sua iniciação científica no laboratório; Juliane Sanches, amiga desde a graduação em Biomedicina na UEL e atual colaboradora; Munick Fulquim e Priscila Raspantini, na época, estudantes de obstetrícia e iniciação científica, importantes colaboradoras durante as etapas iniciais do projeto; Renato Salgado, amigo e importante colaborador científico, obrigado pela valiosa ajuda na correção dos artigos e da tese; Prof. Sebastián San Martín, amigo e colaborador. Fui muito privilegiado em poder conviver e contar com o apoio de todos vocês na realização deste estudo. Formamos uma excelente equipe! Cada um, a sua maneira, fez uma contribuição para este estudo, por isso compartilho-o com vocês. By means of this study our laboratory has developed a new mouse model of pregnancy complicated by long-term type 1 diabetes and evaluated the impact of this disease on the uterine environment at early pregnancy. The age of pregnancy studied (168 hours) comprises the stage in which antimesometrial decidua is fully developed and organogenesis is in progress, of particular interest due to higher rates of malformations in diabetic pregnancies. In addition, the myometrium is at the first adaptative phase of pregnancy (proliferative phase) and diabetic pregnancies are However, no differences were observed between groups. Effects of diabetes on the myometrium were investigated in two subgroups: D1 (90-110D) and D2 (100-110D).Histomorphometrical analysis revealed an increase in the distance between muscle layers in D1, indicating edema, and diminution of the distan...

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Letter to the Editor: Questionable allegation of embryopathy in offspring of diabetic rats

Kalter¹

1998

Teratology

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Reproductive toxicology in animals with induced and spontaneous diabetes

Cited by 25 publications

References 102 publications

Diabetic Embryopathy in C57BL/6J Mice

Diabetic Embryopathy in C57BL/6J Mice

Estabelecimento de um modelo de gestação complicada por diabetes tipo 1 em camundongos: avaliação do seu impacto sobre o ambiente uterino no início da gestação.

Letter to the Editor: Questionable allegation of embryopathy in offspring of diabetic rats

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