Methanol exposure during gastrulation causes holoprosencephaly, facial dysgenesis, and cervical vertebral malformations in C57BL/6J mice

Rogers, John M.; Brannen, Kimberly C.; Barbee, Brenda D.; Zucker, Robert M.; Degitz, Sigmund J.

doi:10.1002/bdrb.20003

Cited by 21 publications

(7 citation statements)

References 41 publications

(42 reference statements)

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“…In the first instance, we asked whether maternal exposure to methanol damaged Adh5 −/− Fancd2 −/− embryos. It is well known that this alcohol is a potent teratogen ( Rogers et al., 2004 ). Timed matings were set up, and females were exposed to methanol or saline intraperitoneally during the first trimester of pregnancy (E7.5).…”

Section: Resultsmentioning

confidence: 99%

Endogenous Formaldehyde Is a Hematopoietic Stem Cell Genotoxin and Metabolic Carcinogen

et al. 2015

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SummaryEndogenous formaldehyde is produced by numerous biochemical pathways fundamental to life, and it can crosslink both DNA and proteins. However, the consequences of its accumulation are unclear. Here we show that endogenous formaldehyde is removed by the enzyme alcohol dehydrogenase 5 (ADH5/GSNOR), and Adh5−/− mice therefore accumulate formaldehyde adducts in DNA. The repair of this damage is mediated by FANCD2, a DNA crosslink repair protein. Adh5−/−Fancd2−/− mice reveal an essential requirement for these protection mechanisms in hematopoietic stem cells (HSCs), leading to their depletion and precipitating bone marrow failure. More widespread formaldehyde-induced DNA damage also causes karyomegaly and dysfunction of hepatocytes and nephrons. Bone marrow transplantation not only rescued hematopoiesis but, surprisingly, also preserved nephron function. Nevertheless, all of these animals eventually developed fatal malignancies. Formaldehyde is therefore an important source of endogenous DNA damage that is counteracted in mammals by a conserved protection mechanism.

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Section: Resultsmentioning

confidence: 99%

Endogenous Formaldehyde Is a Hematopoietic Stem Cell Genotoxin and Metabolic Carcinogen

et al. 2015

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“…The palatoquadrate, fully functional as jaw only in sharks, changes its functions in other vertebrates and, in mammals, becomes the incus of the middle ear and the alisphenoid bone, while the upper jaw is constituted by the dermal elements of premaxilla and maxilla. Craniofacial abnormalities were reported in the literature after exposure to different chemicals (Kay, 1987; Sulik et al, 1988; Rogers et al, 2004). On the contrary, ectopic upper jaw cartilage was only described on mouse embryos exposed to teratogenic dosages of retinoic acid (Morriss‐Kay, 1993), a known morphogen acting during a number of embryogenic processes (gastrulation, hindbrain segmentation, axial segmentation, limb organization, and heart and great vessel formation), switching on the expression of genes of the Hox family (Morriss‐Kay et al, 1991; Gudas, 1994; Clagett‐Dame and Plum, 1997).…”

Section: Discussionmentioning

confidence: 99%

Craniofacial and axial skeletal defects induced by the fungicide triadimefon in the mouse

Menegola

Broccia

Renzo

et al. 2005

Birth Defects Research Pt B

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“…In the same group, we found a case of a cutaneous appendage on the eyelid. No such defect has been reported previously, although there is evidence that ethanol interferes with ocular development, inducing anophthalmia, microphthalmia, hypo-and hypertelorism and cyclopia (33,38) .…”

Section: Tabelamentioning

confidence: 92%

Effect of alloxan-induced diabetes mellitus and ethanol on pregnancy outcome in mice

Peres

Ribeiro

Gutierrez

et al. 2009

J. Bras. Patol. Med. Lab.

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Introduction and objectives: To investigate the effects of ethanol, diabetes mellitus and the combination of both on mouse fetuses. Methods: We used 24 female Swiss mice, dividing them into four groups of 6 each: control (C), ethanol (E), diabetes (D) (blood glucose > 200 mg/dL) and diabetes + ethanol (DE). Diabetes was induced by alloxan (40 mg/kg) on day 7 of pregnancy. Groups E and DE received 4 g/kg of 25% v/v ethanol intraperitoneally, whereas groups C and D received saline. On day 18, all fetuses were harvested. Results: In group DE the following anomalies were found: exencephaly, situs inversus totalis, situs inversus partialis, eyelid skin tag and one animal from group E had pulmonary artery hypoplasia. Ethanol administration partially reverted diabetes-fetal resorption caused by diabetes, yet it induced late fetal death. Both diabetes and ethanol reduced placental diameter and increased its weight. Ethanol had more effect on fetal length in males than in females, however, such bias was not found for diabetes. Ethanol prevented diabetes-induced tail shortening in both genders. Conclusions: These results show that, although ethanol might improve energy metabolism in early gestation, it causes cell damage that leads to cardiovascular, limb and neural tube defects, late fetal death and reduced placental size.

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Methanol exposure during gastrulation causes holoprosencephaly, facial dysgenesis, and cervical vertebral malformations in C57BL/6J mice

Abstract: The types of craniofacial malformations induced in the C57BL/6J mouse by methanol indicate that methanol and ethanol have common targets and may have common modes of action.

Cited by 21 publications

References 41 publications

Endogenous Formaldehyde Is a Hematopoietic Stem Cell Genotoxin and Metabolic Carcinogen

Endogenous Formaldehyde Is a Hematopoietic Stem Cell Genotoxin and Metabolic Carcinogen

Craniofacial and axial skeletal defects induced by the fungicide triadimefon in the mouse

Effect of alloxan-induced diabetes mellitus and ethanol on pregnancy outcome in mice

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