As well as direct effects on the embryo or foetus, foreign compounds can also be teratogenic by influencing the maternal organism or the placenta. Thus, maternal malnutrition or protein deficiency, or a deficiency in one or more vitamins or minerals may lead to effects on the embryo and foetus. As might be expected maternal malnutrition will tend to cause growth retardation. However, vitamin A and folic acid deficiencies cause malformations and embryolethality as well as growth retardation. Trypan blue is believed to be teratogenic to animals with a yolk sac placenta by interfering with the nutrition of the embryo (see above).
A permanent, but partial, decrease in placental blood flow will lead to growth retardation in the embryo. A total cessation of blood flow for a short time (3 h) during organogenesis will cause malformations. Thus, foreign substances which cause vasoconstriction in the placenta may give rise to effects on the embryo indirectly. Exposure of pregnant rabbits to hydroxyurea rapidly results in a large reduction in placental blood flow (77%) which may be the cause of craniofacial and cardiac haemorrhages.
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