Robert A. Ahokas

Cadmium-induced fetal growth retardation: Protective effect of excess dietary zinc

Abstract Reproductive performance and fetal cellular growth and development were investigated in laboratory rats chronically fed low drinking water levels (0, 1.0, 10.0, and 100 μg/ml) of cadmium (Cd), a known embryotoxic trace element, through gestation. Maternal daily food and water consumption, total weight gain, maternal weight gain, and feed efficiency all decreased with increasing Cd consumption. Term fetal weight was significantly less than that of control subjects only in the group fed 100 μg Cd/ml drinking water. Total litter weight, however, gradually decreased with increasing Cd concentration due to reduced litter size. Fetal growth retardation was a result of decreased cell division (DNA) and cell growth (protein/DNA ratio). When dams were pair-fed the average daily amount of food consumed by those fed 100 μg Cd/ml drinking water, maternal weight gain and fetal weight, DNA, and protein/DNA ratio were increased, but not to control levels. Dietary zinc (Zn) supplementation (5.0 μg/ml drinking water) of Cd-fed dams increased maternal food consumption and fetal weight, DNA, and protein/DNA ratio to control levels. Fetal levels of Cd were extremely low (0.038 to 0.095 μg/gm fetus) and did not increase with increasing Cd consumption, while placental Cd increased more than 10-fold. Fetal Zn was decreased in Cd-fed dams, and Zn supplementation increased fetal Zn levels, but not to control levels. These results suggest that Cd-induced fetal growth retardation is an indirect rather than a direct effect, resulting from reduced maternal food consumption and metabolism. Since dietary Zn blocks these effects, Cd may be a result of induced Zn deficiency.

Cadmium uptake by the rat embryo as a function of gestational age.

Maternal blood, liver, kidney, and placental and fetal (embryo) accumulation of cadmium (Cd), a known embryotoxic trace element, was investigated following a single oral dose of various amounts of Cd (10 to 1,000 microgram/rat) as CdCl2 containing 109Cd at days 6, 10, 14, and 17 of gestation. Twenty-four hours after Cd administration the rats were killed and the various tissues were counted in a gamma well counter for determination of 109Cd activity. Maternal liver and kidneys were the main target organs of Cd accumulation at all stages of gestation. Embryo levels of Cd were highest prior to formation of the functional placenta. After placental formation, fetal Cd levels were decreased, while placental accumulation of Cd increased with increasing gestational age. The results indicate that the embryo accumulates the greatest percentage of ingested Cd between implantation and placentation, the early period of organogenesis. The placenta apparently protects the fetus from exposure to this element during the last third of gestation.

The effect of salinity and temperature on intracellular osmoregulation and muscle free amino acids in Fundulus diaphanus

Abstract 1. 1. Fundulus diaphanus tolerates both freshwater and 30‰ sea water at 15°C. At 0.5°C only freshwater was tolerated well, and only 50% of the sample population survived in 30‰ sea water after 2 weeks. 2. 2. At 15°C tissue inorganic ions and free amino acids increased with an increase in ambient salinity. In freshwater adapted fish, tissue K + increased while free amino acids decreased with a decrease in water temperature. 3. 3. The primary amino acids involved with salinity change were alanine, glycine, serine, proline, and aspartic acid. Taurine did not change with salinity and apparently does not function in intracellular osmoregulation.

Cardiac output and uteroplacental blood flow in diet-restricted and diet-repleted pregnant rats

Cardiac output and uteroplacental blood flow were measured with 15 mu radioactive microspheres in anesthetized pregnant rats which were fed: (1) ad libitum throughout gestation; (2) a 50% restricted diet from day 5 of gestation; and (3) a 50% restricted diet from days 5 to 13 of gestation and ad libitum from day 14 of gestation. An additional group of nonpregnant rats fed ad libitum was also used. Dietary restriction caused a net maternal weight loss and a 20% reduction in mean fetal weight and mean placental weight by day 21 of gestation. Restricted dams fed ad libitum during the last week of gestation showed a net maternal weight gain, while mean fetal weight, but not placental weight, was near that of the ad libitum--fed controls. In the diet-restricted rats, total cardiac output was reduced 30% relative to controls by days 20 and 21 of gestation, but cardiac output per unit maternal body weight was not significantly different. Dietary restriction decreased both total uterine and placental blood flow by about 65%. Diet repletion late in gestation did not significantly increase total cardiac output or cardiac output per unit body weight. Total uterine and placental blood flows were near those of controls, primarily because of an increased fraction of cardiac output distributed to the uterus.

Effects of dietary lead and zinc on pregnancy

In order to further understand the effects of ingested Pb on pregnancy and the possible interaction of the trace element Zn with Pb, groups of dated pregnant rats were fed 10, 50, 100, 200, or 500 mg/L of Pb in water throughout pregnancy. A control group with no Pb, but diet ad lib, and a pair-fed control group with no Pb were also studied. Maternal average daily food consumption was significantly reduced at 50 mg/L of Pb and up. Total and net maternal weights were significantly reduced at 50 mg/L of Pb and up. Pair feeding at the 200 mg/L level improved maternal weight gain but not to control levels. Zn, 200 mg/L, supplement at the 200 mg/L of Pb level caused no improvement nor did ad lib diet with Pb removed after 16 days. Fetal weight decreased progressively as Pb levels were increased. Pair feeding at the 200 mg/L Pb of level and Zn, 200 mg/L, supplement with 200 mg/L of Pb significantly increased fetal weight but not to control levels. Placental weight was unchanged throughout. The results indicate that Pb-induced fetal growth retardation is due to reduced maternal food and energy intake, as well as to direct effect on the fetus. Excess dietary Zn improves fetal growth, probably by increasing maternal food consumption.

HEAT SHOCK PROTEIN 70 IS NOT INCREASED IN WOMEN WITH SEVERE PREECLAMPSIA

Objective: The purpose of this study is to determine if heat shock protein 70 (Hsp 70), a marker of cellular stress, is elevated in pregnancies complicated by severe preeclampsia. Methods: Maternal blood was collected from women with severe preeclampsia (n=47) matched for delivery gestational age to normotensive pregnant controls (n=51). Hsp 70 concentrations were measured by standard ELISA techniques. Data were analyzed with the Students t-test and chi-square test. Main outcome measures: The primary outcome measured was Hsp 70 concentrations. Our hypothesis prior to data collection was that HSP 70 would be increased in women with severe preeclampsia. Results: Compared with normotensive women, those with severe preeclampsia had similar maternal age, parity, delivery gestational age, maternal weight, and ethnicity. There was no difference in mean concentrations of Hsp 70 between women with severe preeclampsia and controls (35.4±96.7 vs. 30.1±11.5, p=0.80). Similar numbers of women with severe preeclampsia (n=28) and controls (n=30) had Hsp 70 concentrations below the 0.02 ng/dL level of detection (chi-square value=0.024, p=0.88). Conclusion: Hsp 70 concentrations are not elevated in women with severe preeclampsia.

The effect of hydralazine on placental perfusion in the spontaneously hypertensive rat

Intravenous hydralazine was administered to 16 spontaneously hypertensive rats on day 21 of gestation. The radioactive labeled microsphere technique was used to assess the change in organ perfusion produced by the drug. Vascular resistance to most organs was decreased, except to the placentas, stomach, and cecum, where it increased by 43%, 104%, and 44%, respectively. Blood flow to the organs was redistributed, and although it was increased to the lungs, kidneys, liver, and adrenals, it was significantly reduced to the spleen, stomach, placentas, cecum, large intestine, and pancreas. The effect of hydralazine on placental perfusion was opposite to the effect on the uterus (myometrium). Patients with the highest blood pressures tend to have the poorest placental perfusion. Intravenous hydralazine should be used cautiously in these patients.

Placental transfer of intravenous fluoride in the pregnant ewe

Fluoride ion is produced with the biotransformation of two commonly used anesthetics, methoxyflurane and enflurane. Fluoride ion is added to prenatal vitamin preparations and water to prevent carious teeth. Very high levels of fluoride assailure. Previous studies of placental transfer of fluoride ion were conflicting. Our study in pregnant ewes revealed rapid transfer of the fluoride ion across the placenta with high fetal to maternal ratios as early as 1 minute.

Effects of dietary lead and zinc on fetal organ growth

In order to further understand the effects of ingested lead (Pb) on the fetus and the possible interaction of the trace element zinc (Zn) with Pb, groups of rats with dated pregnancies were fed 0, 10, 50, 100, 200 or 500 mg/L of Pb in water throughout pregnancy. Diet was provided ad libitum. A group pair fed with the 200 mg/L of Pb group and a group fed both Zn and Pb, 200 mg/L, were also studied. Placental weight remained constant, but cell division and total protein level were decreased while cell size increased markedly. Fetal carcass and liver weight, cell division, and protein were decrease while cell growth was unchanged. Brain weight decreased while cell division, growth, and protein were unchanged. Kidney weight, cell division and protein level were unchanged but cell growth was decreased. Organ dry weight varied with wet weight while the percentage of water was unchanged. Whether pair feeding and Zn supplements improve carcass and liver weight is questionabel.

Placental transfer of 14C-hexoprenaline

The placental transfer of a single intravenous injection of 14C-hexoprenaline was studied in eight pregnant New Zealand white rabbits. Maternal and fetal blood was sampled intermittently for 60 minutes after the injection. An initial rapid decrease in the levels of 14C-hexoprenaline in maternal blood was followed by a second slower phase, whereas fetal levels remained insignificant. The conclusion, therefore, is that the rapid improvement in fetal heart rate after the administration of a single maternal intravenous injection of hexoprenaline in the treatment of fetal distress is due to the action on the uterus and/or on maternal cardiovascular function, and not to direct stimulation of the fetus.