Effects of massive doses of ergocalciferol plus cholesterol on pregnant rats and their offspring.

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 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 abnormal aorta, in the lung and pleura, in the gastoinstestinal tract, and in the kidney. This is in contrast to the atherosclerosis described in nonpregnant rats fed a similiar 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 lesionsassociated with a generalized retardation of ossification, placental edema, or calcification accompanied by a loss of the normal structure of the placenta and degenerative manifestation 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.

Histochemical study of metrial gland cells through the last week of pregnancy in the albino rat.

The metrial gland cells of the rat were studied from day 16 to 21 of pregnancy through enzyme histochemistry. The following enzyme activities were tested: 2 carboxylic esterases, 4 phosphatases, 1 aminopeptidase and 10 dehydrogenases including 4 which are involved in steroid metabolism. Although acid phosphatase activity was strong in mesenchymal cells, it remained undetected in large, sometimes binucleate cells lining central and subplacental vessels of the mesometrial triangle. 5-Bromo-indoxyl acetate esterase was likewise absent from the parietal vascular cells of the central artery. The study of 6 enzyme activities, i.e., GPDH, 3-OU-BDH, G6PDH, 3-B-HSDH, primary and secondary alcohol dehydrogenases, allowed to conclude that metrial gland cells are actively involved in steroidogenesis and lipid catabolism. Maternal origin of this gland can be sustained with reference to the pattern of acid phosphatase, indoxyl-esterase and some oxidoreductases II activities distribution which appears to be different from what is found in the trophospongium area.

Effects of amethopterin (methotrexate) on the evolution of pregnancy in rats.

Amethopterin (4-amino-N-10-methyl-glutamic acid) was given to pregnant rats in varying doses at different periods of gestation to evaluate its effects upon both the mother and the fetoplacental unit. The maternal organism is more sensitive to this drug at days 14 to 17 than at a larger stage of gestation. When administered to rats from day 14 to day 18 of pregnancy the drug is capable of inducing a series of deleterious effects: maternal weight loss, resorption, abortion or hypotrophy of fetuses. Day 16 appears to be a critical moment in the evolution of rat pregnancy, after which injection of amethopterin does no longer impair fetoplacental growth. Before this date, the drug directly inhibits fetal weight gain, whereas the sensitivity of the placenta is only transient at day 16 resulting in maximum weight decrease of this organ 24 h later. Its action on rat pregnancy follows a direct dose-effect relationship reflecting increasing damage to the products of conception (resorption, abortion and hypotrophy).

PIP: Varying doses of amethopterin were injected intraperitoneally into S prague-Dawley and Wistar rats at different periods of gestation to evalu ate the effects on rat pregnancy and fetal outcome. Anorexia, diarrhea and vaginal bleeding were observed with repeated doses of more than .5 mg/kg. When administered for 5 consecutive days, a weight loss of up to 49.93 gm was observed. 5 daily doses of 1.5 mg/kg or more resulted in a 100% death rate of Sprague-Dawley rats. Abortions were common in Wistar rats given a dose higher than .5 mg/kg. A 100% resorption rate was observed in Wistern rats given 2.0 mg/kg for 5 days. Hypotrophic fetuses were observed in both strains when .5 mg/kg was administered for 5 days. Fetal growth rate was significantly lower from day 14 to day 17 of drug treatment, whcih seemed to be the time when the animals are most sensitive to the drug. The effects of amethopterin before day 17 follow a direct dose-effect relationship.