metallothionein and Fetal-Growth-Retardation

Cadmium (Cd) is linked with increased risk of fetal growth restriction (FGR). Nevertheless, the mechanism remains unknown. This study established a mouse model of Cd-induced FGR through two exposure methods. Pregnant mice were either administered with CdCl2 (5, 50 and 250ppm) throughout pregnancy through drinking water or intraperitoneally injected with CdCl2 (4.5mg/kg) on GD9. As expected, fetal weight and crown-rump length were reduced in a gender-independent manner. Interestingly, Mt1 and Mt2, two metallothionein genes, were up-regulated in maternal liver. Correspondingly, Cd accumulated mainly in maternal liver and kidney, and only trace amounts of Cd could pass from dam to placentas and fetuses. Further analysis showed that placental Zn concentration was elevated. Conversely, embryonic Zn concentration was reduced. Moreover, placental Znt1 and Znt2, two zinc transporters, were down-regulated in Cd-exposed mice. These results suggest that maternal Cd exposure during pregnancy reduces placental Zn transport and induces fetal growth restriction.

Topics: Animals; Cadmium; Cation Transport Proteins; Down-Regulation; Environmental Pollutants; Female; Fetal Blood; Fetal Growth Retardation; Liver; Maternal-Fetal Exchange; Metallothionein; Mice; Placenta; Pregnancy; Zinc

Intrauterine growth restriction (IUGR) is a pleiotropic complication of pregnancy. Prematurity and growth abnormalities are common risk factors for perinatal morbidity and mortality. Free radical damage has been recognized as a common pathogenic mechanism of many neonatal diseases. The aim of the present study was to characterize the possible links between the level of maturity, the birthweight and the antioxidant status of neonates born with IUGR. Our data suggest that the stress markers measured on the cord blood of neonates with IUGR and mature, healthy neonates do not necessarily reflect the extent of oxidative stress. However, significant correlations were found between the maturity of the neonates with IUGR and the oxidative damage. The mature IUGRs exhibited ONOO(-) accumulation and increased lipid peroxidation more frequently as compared with the pre-term group. The results suggest that the oxidative injury in IUGR may depend on the level of maturity and the birthweight.

Topics: Birth Weight; Catalase; Erythrocytes; Female; Fetal Blood; Fetal Growth Retardation; Heme Oxygenase (Decyclizing); Humans; Hydrogen Peroxide; Infant, Newborn; Male; Metallothionein; Oxidation-Reduction; Peroxynitrous Acid; RNA, Messenger; Superoxide Dismutase

Exposure to tobacco smoke during pregnancy may result in intrauterine growth restriction (IUGR). In the study, the effect of tobacco smoke on vascular flows in the middle cerebral artery, umbilical artery, ductus venosus in fetuses and uterine artery in pregnancies complicated by IUGR was investigated. The study subjects were divided into three groups: smoking women with IUGR (n=31), women with idiopathic IUGR (n=28) and healthy controls (n=50). Fetal biometry and flow parameters were measured. Concentration of heavy metals and antioxidants was tested in maternal blood and fetal umbilical cord blood. The Student t test and multiple regression analysis were used. Cotinine and cadmium concentrations were significantly higher in smokers (55.23±54.23, 1.52±0.9), while metallothionein was significantly higher (22.94±8.64) in the idiopathic IUGR group. Strong correlations between cotinine and cadmium concentrations and cerebral-umbilical index were found. Long-term exposure to tobacco smoke deteriorates flows in vital fetal vessels.

Topics: Blood Circulation; Cadmium; Cotinine; Female; Fetal Growth Retardation; Glutathione; Humans; Metallothionein; Nicotiana; Pregnancy; Smoking

Maternal cadmium exposure induces fetal growth restriction (FGR), but the underlying mechanisms remain largely unknown. The placenta is the main organ known to protect the fetus from environmental toxins such as cadmium. In this study, we examine the role of the two key placental factors in cadmium-induced FGR. The first is placental enzyme 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2), which is known to protect the fetus from exposure to high cortisol levels and subsequently FGR, and the second the cadmium binding/sequestering proteins metallotheionein (MT)-I and -II. Using the MT-I/II(-/-) mouse model, pregnant mice were administered cadmium, following which pups and placentas were collected and examined. MT-I/II(-/-) pups exposed to cadmium were significantly growth restricted, but neither placental weight nor 11β-HSD2 was altered. Although cadmium administration did not result in any visible structural changes in the placenta, increased apoptosis was detected in MT-I/II(-/-) placentas following cadmium exposure, with a significant increase in levels of both p53 and caspase 3 proteins. Additionally, glucose transporter (GLUT1) was significantly reduced in MT-I/II(-/-) placentas of pups exposed to cadmium, whereas zinc transporter (ZnT-1) remained unaltered. Taken together, these results demonstrate that MT-I/II(-/-) mice are more vulnerable to cadmium-induced FGR. The present data also suggest that increased apoptosis and reduced GLUT1 expression in the placenta contribute to the molecular mechanisms underlying cadmium-induced FGR.

Topics: Animals; Apoptosis; Cadmium; Carrier Proteins; Caspase 3; Female; Fetal Growth Retardation; Genetic Predisposition to Disease; Glucose Transporter Type 1; Maternal-Fetal Exchange; Metallothionein; Mice; Mice, Knockout; Placenta; Pregnancy; Tumor Suppressor Protein p53

The aim of this study was to investigate the influence of cigarette smoking on the pro/antioxidant balance in pregnant women with intrauterine growth restriction (IUGR). The studies have shown a 2-fold increase of Cd concentration in blood of women with IUGR in labour and a 10-fold increase in smoking pregnant women with IUGR. The increase of malondialdehyde concentration in plasma and 8-hydroxydeoxyguanosine in serum and Cu/Zn superoxide dismutase activity in erythrocyte lysate of pregnants with IUGR, reinforced by smoking, was revealed. We observed a decrease in the concentration of glutathione in blood and glutathione peroxidase activity in plasma and in erythrocyte lysate. A 4-fold higher metallothionein concentration in the plasma of women with IUGR in labour suggests that metallothionein may be one of the IUGR markers. Metallothionein concentration was intensified by smoking up to 7-fold in comparison to the controls. The pro/antioxidant balance during pregnancy is significantly affected by smoking.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Antioxidants; Cadmium; Copper; Cotinine; Deoxyguanosine; Environmental Pollutants; Female; Fetal Blood; Fetal Growth Retardation; Glutathione; Glutathione Peroxidase; Humans; Lead; Malondialdehyde; Metallothionein; Pregnancy; Smoking; Superoxide Dismutase; Young Adult; Zinc

Ethanol, under certain conditions, alters the metabolism of sulfur amino acids, metallothionein (MT) and zinc. If chronic ethanol administration during pregnancy decreases the availability of sulfur amino acids or Zn, this deficiency could contribute to growth retardation of the fetuses, one of the features of fetal alcohol syndrome. The purpose of this study was to discern whether chronic ethanol administration to pregnant rats alters glutathione (GSH), MT or Zn content of selected tissues of the dams and fetuses. Sprague-Dawley rats were fed from gestational days 5 to 19 either the control diet ad libitum (AF), the ethanol diet ad libitum (EF) or the control diet using the pair-feeding technique (PF). On the 19th day of gestation, total hepatic GSH was significantly lower for the EF and PF dams than for the AF dams. Hepatic MT contents were similar for the AF and EF dams, and hepatic MT content was significantly greater for the PF dams than the AF and EF dams. The three groups did not differ regarding hepatic Zn content of dams or fetuses. In summary, on the 19th day of gestation, chronic ethanol feeding of pregnant rats did not lower the maternal hepatic GSH level below that of PF dams, did not induce hepatic MT in the dams and did not prevent fetuses from achieving body weights and hepatic Zn concentrations equal to those of controls.

Topics: Animals; Birth Weight; Body Weight; Ethanol; Female; Fetal Alcohol Spectrum Disorders; Fetal Growth Retardation; Fetus; Glutathione; Litter Size; Liver; Metallothionein; Organ Size; Pregnancy; Pregnancy, Animal; Rats; Rats, Inbred Strains; Zinc