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Effects of Massive Doses of Ergocalciferol Plus Cholesterol on Pregnant Rats and Their Offspring¹

Laboratory of Gynecology and Human Reproduction, Research Unit, St-Pierre Hospital, 322 Rue Haute, 1000 Brussels, Belgium, and Laboratory of Pathological Chemistry, Faculty of Medicine, Free University of Brussels, 2 Rue Evers, 1000 Brussels, Belgium

Ergocalciferol (320,000 or 480,000 IU/kg) plus cholesterol (60 mg/kg) in olive oil solution was administered daily on 1, 2, or 4 consecutive days to pregnant rats from days 9, 10, 14, or 18 of gestation. The control animals received only olive oil. Disseminated lesions of metastic calcinosis were found in various tissues, in the coronary arteries and myocardium, in the media of the abdominal aorta, in the lung and pleura, in the gastrointestinal tract, and in the kidney. This is in contrast to the atherosclerosis described in nonpregnant rats fed a similar diet. A significant decline in maternal weight as well as a high rate of morbidity and mortality was observed. In mothers killed on day 22 of pregnancy, fetal and placental growths appeared significantly retarded, suggesting a direct effect of the steroid or its more active metabolite, 1,25-dihydroxycholecalciferol, on the fetus or the trophoblastic tissue. Fetal bone lesions associated with a generalized retardation of ossification, placental edema, or calcification accompanied by a loss of the normal structure of the placenta and degenerative manifestations at this level were observed. Moreover, we noted a striking alteration of the fetal face in 33–39% of experimental fetuses, called by us carnival fetuses.

KEY WORDS: • ergocalciferol • pregnancy • mediacalcinosis

¹ Supported by grants from the Ford Foundation (no. 670-0465 A) and the Fonds de la Recherche Scientifique Médicale (no. 20401). Dr. K. Tshibangu is a recipient of the Ford Foundation fellowship.

Manuscript received 17 October 1974.