Placental cadmium as an additional noninvasive bioindicator of active maternal tobacco smoking.

Tobacco smoke (TS) is a mixture of chemicals that is known to exert carcinogenic and endocrine-disrupting effects, as well as adverse effects on various systems. In TS nicotine is the major alkaloid and cadmium (Cd) the most abundant metal ion. The aim of this investigation was to assess exposure to Cd attributed to TS in healthy postpartum subjects (mean age 28 years) after term vaginal delivery in a clinical hospital by determining metal levels in maternal blood, placenta, and cord blood in relation to nicotine in maternal hair (12-cm-long samples). Two study groups were compared based upon self-reporting data: smokers (n = 32; continual cigarette smoking 3 months before and 9 months during pregnancy) and nonsmokers (n = 54; including passive smokers whose parameters did not differ from unexposed nonsmokers). In smokers compared to nonsmokers maternal hair nicotine concentrations increased approximately sevenfold, while Cd levels rose fourfold in maternal blood and up to twofold in placenta. Significant positive correlations were noted between maternal hair nicotine and placental Cd, maternal hair nicotine and maternal blood Cd, and placental Cd and maternal blood Cd. Levels of cord blood Cd were low in both study groups (<0.1 ng/ml). Data indicate that Cd in placenta may serve as a noninvasive bioindicator in addition to commonly used noninvasive hair nicotine in maternal TS assessment, especially in cases where unavailable or inappropriate (short or chemically treated) hair samples occur.

The effects of maternal cigarette smoking on cadmium and lead levels, miRNA expression and biochemical parameters across the feto-placental unit.

Several miRNAs have been previously identified to be associated with cigarette smoke and/or the toxic metals cadmium (Cd) and lead (Pb). The aim of this study was to investigate the associations of maternal cigarette smoking with cadmium (Cd) and lead (Pb) levels, candidate miRNA expression and biochemical parameters across the feto-placental unit. miRNAs were isolated according to protocols provided by manufacturer from 72 healthy postpartum women using Qiagens' kits based on phenol/guanidine samples lysis and silica-membrane purification of total RNA. Candidate miRNAs (miR-1537, miR-190b, miR-16, miR-21, and miR-146a) were quantified by real-time PCR. Biochemical parameters were analyzed in plasma samples by standardized and harmonized enzymatic methods using appropriate calibrators, while CRP was determined by immunoturbidimetric method. Concentration of Cd and Pb in whole blood and placenta samples were measured by inductively coupled plasma mass spectroscopy. Cd levels in smokers were higher in all of the analyzed compartments of the feto-placental unit, Pb in maternal blood and placenta than non-smokers. Smokers also had a higher expression of miR-16 in maternal and miR-146a in cord plasma, and lower expression of miR-21 in the placenta in comparison to non-smokers. Urate concentrations in the maternal plasma of smokers were lower than this value in non-smokers. The study has demonstrated that maternal smoking was associated with toxic metals (Cd and Pb) levels, urate concentration and alteration of miRNA expression. Given that the effects of maternal smoking on miRNA expression are inadequate, all compartments of the feto-placental unit should be analyzed to obtain a complete picture. This paper is the first to report on the results of expression of cellular and circulating miRNAs simultaneously in maternal and fetal compartments and in the placenta.

Metallothionein 2A gene polymorphism and trace elements in mother-newborn pairs in the Croatian population.

The main source of exposure for all essential and toxic elements in the general population is diet. In smokers, the main route for cadmium (Cd) and lead (Pb) intake is the inhalation of tobacco smoke. Besides gender, age, nutrition, lifestyle, and physiological conditions such as pregnancy, specific genetic characteristics also influence individual element uptake. Metallothionein MT2 is a cysteine-rich low-weight protein found ubiquitously throughout the body. Specific gene polymorphism may influence MT2 expression and subsequent binding, transfer and organ accumulation of metals, though data on these influences are lacking, especially in human mother-newborn pairs. The objective of this study was to determine selected toxic (Cd, Pb, Hg) and essential (Fe, Zn, Cu, Se) elements in maternal blood, placenta, and cord blood (by ICP-MS), and MT2 levels in maternal serum (by ELISA) in relation to maternal MT2A -5A/G (rs28366003) polymorphism (by RFLP-PCR and electrophoresis). Study participants were healthy postpartum women in Croatia (n=268, mean age 29 years) with term vaginal childbirth in a maternity ward assigned into two study groups by self-reporting about their smoking habit (by questionnaire). Smokers vs. non-smokers had increased levels of Cd and Pb in all measured samples, Fe and Cu in cord blood, Zn in placenta, and MT2 in maternal serum. Among subjects with AG/GG genotype, placental Fe was significantly lower only among non-smokers, while MT2 levels in serum were lower, though not significantly, regardless of maternal smoking habit. There was no impact of MT2A -5A/G SNP on any element in maternal or cord blood. In conclusion, the results confirmed maternal smoking-related increases in Cd and Pb levels in the maternal-placental-foetal unit. They also provided additional data on concomitant metal concentrations in representative samples of maternal blood, placenta, and cord blood, as well as increased cord blood Fe and Cu, placental Zn, and maternal serum MT2 in smokers. New evidence is that MT2A -5A/G SNP was associated with decreased placental Fe levels in non-smokers. For a final conclusion on the influence of the MT2A -5A/G polymorphism on toxic and essential element levels in mother-newborn pairs, further research would require a larger number of participants divided across subgroups defined by the main source of particular toxic metal exposure (such as specific food intake, cigarette smoking, air pollution and/or occupational exposure).