In most mammalian species examined, the levels of calcium (1-4) and of phosphorus (5-7) in the blood of the fetus at term exceed those of the dam. The difference in serum calcium between mother and fetus may, in part, be explained by the observation that the circulating level of this element in the dam falls in the final stages of gestation (5,8,9). In addition, in the many mammals investigated, the level of calcium in the blood of the fetus has been shown to increase as termination of pregnancy is approached (10-12). Finally, in the rat, fetal phosphatemia has been shown to parallel the rise in blood calcium in the last days before birth (13).We have previously demonstrated that rat fetuses are acidotic near term, and that in utero hypercalcemia and early neonatal hypocalcemia are associated with low blood pH and normalization of blood pH, respectively (14). In view of this apparent association at term and immediately after birth, the present studies were undertaken: (i) to investigate whether in the final stages of gestation fetal blood pH shifts concurrently with reported alterations in the levels of calcium and phosphorus; and (ii) to test the hypothesis that changes in the circulating levels of calcium and phosphorus are causally related to blood pH in the developing mammal in utero, by either aggravating or alleviating the acidotic state of the conceptus by the maternal administration of ammonium chloride or sodium bicarbonate, respectively.Materials and methods. Four-to eightmonth-old pregnant albino rats and their offspring were used. The adult animals were maintained on Purina laboratory chow and tap water ad libitum and housed in a temperature-controlled room illuminated on a 14hr-light/ 10-hr-dark cycle.In order to obtain females at a known time Work supported by National Institutes of Health Grant HD 07419-3.of gestation, the animals were caged with males for a single overnight period. The day of mating was counted as Day 0, and experiments were terminated at preselected times during the last week of pregnancy.
Studies on fetuses in the final week of gestation.Beginning on Day 17 and then daily through the 22nd day of pregnancy, groups of animals were handled as follows:The gravid female was lightly anesthetized with ether, a laparotomy was performed, and the pregnant uterus was exposed. Fetuses were sequentially bled and excised until the entire litter was sampled. Fetal blood was taken from the axilla while the placental and umbilical circulations were intact. Tail blood was drawn from the mother at the beginning and end of each experiment.Studies on offspring of pregnant animals receiving either ammoniunt chloride or sodium bicarbonate orally. Pregnant animals were divided into three groups. Beginning on the 17th day of gestation, tap water was removed and the following substitutions were made. One group of animals was given a solution of 1.5% NH4Cl, the second group received a 1.5% solution of NaHC03, and the remaining rats were given distilled water. Animals were allowed to drink freely and fluid...