Title: Toxicity of cadmium in the perfused human placenta.

Authors: Wier, P J; Miller, R K; Maulik, D; DiSant'Agnese, P A

Published In Toxicol Appl Pharmacol, (1990 Aug)

Abstract: Cadmium, a placental toxicant in rodents, was studied in the in vitro isolated dually perfused human placental lobule for periods of up to 12 hr to determine if cadmium can also be toxic in the human placenta. Placental lobules were perfused with a modified M199 medium containing 0, 10, 20, or 100 nmol of cadmium chloride/ml added only initially to the maternal perfusate. Every 4 hr, the perfusates in both the maternal and the fetal circuits were replaced with fresh perfusate containing no Cd. Measurements during perfusion were oxygen consumption, net fetal oxygen transfer, fetal pressure, fetal volume loss, glucose utilization, lactate production, human chorionic gonadotropin (hCG), and zinc transfer. Postperfusion, morphology, and tissue slice studies were performed to evaluate cellular metabolic function and uptake of an amino acid (alpha-[14C]-aminoisobutyric acid). In all cadmium experiments, there were no significant alterations in oxygen consumption, lactate production, glucose utilization, or amino acid uptake compared with controls; however, there were dose-related changes in the synthesis and release of the protein hormone, hCG, beginning within 4 hr of initial exposure to Cd. There were also dose-related volume loss from the fetal vasculature (greater than 6 ml/hr) and ultrastructural changes (subsyncytiotrophoblastic vesiculations, stromal edema, vacuoles in Hofbauer cells), with necrosis at 100 nmol Cd/ml occurring between 5 and 8 hr. Cadmium (10 nmol/ml) reduced the placental transfer of zinc into the fetal circuit. Thus, the human placenta is a site for toxic action of cadmium and is at least as sensitive as the rodent placenta to the actions of cadmium. In addition, these human studies demonstrated a selectivity in the toxic effects with a maintenance of carbohydrate metabolism and amino acid uptake even after 12 hr of exposure with placental Cd burdens of 151 +/- 37 nmol/g, but with the earliest (within 4 hr) dose-related functional alterations occurring in protein hormone production and zinc transfer followed by later changes in morphology with a tissue Cd burden of 46.5 +/- 4.0 nmol/g.

PubMed ID: 2392803

MeSH Terms: Amino Acids/metabolism; Cadmium/metabolism; Cadmium/toxicity*; Chorionic Gonadotropin/metabolism; Female; Fetus/blood supply; Glucose/metabolism; Humans; In Vitro Techniques; Lactates/biosynthesis; Lactic Acid; Oxygen Consumption/drug effects; Placenta/drug effects*; Placenta/metabolism; Placenta/pathology; Pregnancy; Zinc/metabolism