Experimental Production of Congenital Anomalies

Ingalls, Theodore H.; Curley, Francis J.; Prindle, Richard A.

doi:10.1056/nejm195211132472004

Cited by 164 publications

(24 citation statements)

References 20 publications

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“…These anomalies were the most prominent defects observed in the present study. Moreover, hydramnios, also observed in this study in association with every case of excncephaly, wits present where anencephalic fetuses were found in the above study (4). Also, lngalls and Curley (30), in another investigation, found cranioschisis.…”

Section: Discussionsupporting

confidence: 77%

Morphine-Induced Fetal Malformations HI: Possible Mechanisms of Action

Arcuri

Gautieri

1973

Journal of Pharmaceutical Sciences

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Section: Discussionsupporting

confidence: 77%

Morphine-Induced Fetal Malformations HI: Possible Mechanisms of Action

Arcuri

Gautieri

1973

Journal of Pharmaceutical Sciences

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“…Ingalls et al (1952) investigated the effect of simulated altitude on pregnant mice. The mice were placed in a low-pressure chamber connected to a vacuum pump and the oxygen tension was reduced to the equivalent of 25,000-27,000 feet.…”

Section: High Altitudementioning

confidence: 99%

The effect of hypoxia in development

Webster

Abela

2007

Birth Defects Research Pt C

174

135

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There is increasing evidence that the oxygen supply to the human embryo in the first trimester is tightly controlled, suggesting that too much oxygen may interfere with development. The use of hypoxia probes in mammalian embryos during the organogenic period indicates that the embryo is normally in a state of partial hypoxia, and this may be essential to control cardiovascular development, perhaps under the control of hypoxia-inducible factor (HIF). A consequence of this state of partial hypoxia is that disturbances in the oxygen supply can more easily lead to a damaging degree of hypoxia. Experimental mammalian embryos show a surprising degree of resilience to hypoxia, with many organogenic stage embryos able to survive 30-60 min of anoxia. However, in some embryos this degree of hypoxia causes abnormal development, particularly transverse limb reduction defects. These abnormalities are preceded by hemorrhage/edema and tissue necrosis. Other parts of the embryo are also susceptible to this hypoxia-induced damage and include the genital tubercle, the developing nose, the tail, and the central nervous system. Other frequently observed defects in animal models of prenatal hypoxia include cleft lip, maxillary hypoplasia, and heart defects. Animal studies indicate that hypoxic episodes in the first trimester of human pregnancy could occur by temporary constriction of the uterine arteries. This could be a consequence of exposure to cocaine, misoprostol, or severe shock, and there is evidence that these exposures have resulted in hypoxia-related malformations in the human. Exposure to drugs that block the potassium current (IKr) can cause severe slowing and arrhythmia of the mammalian embryonic heart and consequently hypoxia in the embryo. These drugs are highly teratogenic in experimental animals. There is evidence that drugs with IKr blockade as a side effect, for example phenytoin, may cause birth defects in the human by causing periods of embryonic hypoxia. The strongest evidence of hypoxia causing birth defects in the human comes from studies of fetuses lacking hemoglobin (Hb) F. These fetuses are thought to be hypoxic from about the middle of the first trimester and show a range of birth defects, particularly transverse limb reduction defects. Birth Defects Research (Part C) 81: [215][216][217][218][219][220][221][222][223][224][225][226][227][228] 2007. V C 2007 Wiley-Liss, Inc.

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“…The greater body weight loss in the first 2 days after the exposure to MIC in pregnant animals that did not retain pregnancy as compared with those that did retain pregnancy indicates either an early onset of fetal toxicity or a relationship between marked maternal toxicity and ultimate fetal loss. The magnitude of hypoxia that results from these exposures (8,12) may not explain such marked fetal toxicity in light of the fact that in mice, marked hypoxia induced by other techniques was found to exert far less fetal toxicity than was observed in these other studies (13).…”

Section: Discussionmentioning

confidence: 73%

Epidemiological and experimental studies on the effects of methyl isocyanate on the course of pregnancy.

Varma¹

1987

Environ Health Perspect

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Although press reports indicate that the leakage of methyl isocyanate (MIC) on December 3, 1984, in Bhopal has led to an increase in spontaneous abortions, stillbirths, infant mortality, and fetal abnormalities, no clinical or experimental studies on the reproductive toxicity of MIC were reported in scientific journals for several months after the accident. We therefore conducted, 9 months after the accident, a preliminary survey of 3270 families in Bhopal and experimental studies on the effects of MIC in pregnant mice. It was found that 43% of pregnancies in women residing near the Union Carbide pesticide plant did not result in the birth of a live child. Likewise, exposure of mice to relatively low concentrations of MIC (9 and 15 ppm) for 3 hr caused complete resorption in more than 75% of animals. A decrease in fetal and placental weights was observed at 2 to 15 ppm MIC. In general, the experimental findings in mice corroborate the epidemiological data from Bhopal. The mechanism of the fetal toxicity of MIC remains to be established.

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Experimental Production of Congenital Anomalies

Cited by 164 publications

References 20 publications

Morphine-Induced Fetal Malformations HI: Possible Mechanisms of Action

Morphine-Induced Fetal Malformations HI: Possible Mechanisms of Action

The effect of hypoxia in development

Epidemiological and experimental studies on the effects of methyl isocyanate on the course of pregnancy.

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