Accumulation of cadmium in human placenta interacts with the transport of micronutrients to the fetus
Introduction
Cadmium (Cd) is a widespread, highly toxic environmental pollutant present in human food, especially cereals, potatoes, and vegetables (Olsson et al., 2002). Another major source of Cd is tobacco smoke, resulting in higher blood Cd concentrations in smokers compared to non-smokers (Olsson et al., 2002). Cadmium has a long half-life in the body, and adverse effects of chronic Cd exposures on kidneys and bone are well documented (Åkesson et al., 2005, Åkesson et al., 2006, Staessen et al., 1999). Recently, Cd exposure has been associated with several endocrine effects (Åkesson et al., 2008, Johnson et al., 2003, Piasek et al., 2001).
Experimental studies indicate that the prenatal period is a critical window of Cd exposure. In rats, in utero exposure to Cd was found to induce earlier onset of puberty and changes in the mammary gland of female offspring (Johnson et al., 2003). In addition, prenatal Cd exposure was found to affect postnatal immune function (Hazelhoff Roelfzema et al., 1989). Studies on women at delivery have shown that the Cd concentration in umbilical cord blood could reach between 10% and 70% of the concentration found in maternal blood (Baranowska, 1995, Kantola et al., 2000, Korpela et al., 1986, Lagerkvist et al., 1993, Osman et al., 2000, Soong et al., 1991). Whether this variation is due to nutritional or other factors influencing placental transfer of Cd, or merely due to difficulties in correctly measuring the low Cd concentrations in umbilical cord blood is not known. Cadmium is known to accumulate in the human placenta (Korpela et al., 1986, Osman et al., 2000), which may indirectly affect the fetus. Human placenta perfused with high concentrations of Cd impaired the transfer of zinc (Zn) from the maternal to fetal circulation (Wier et al., 1990).
As to the mechanism behind a Cd–Zn interaction it has been proposed that the accumulation of Cd in placenta induces the synthesis of the metal binding protein metallothionein (MT), which could lead to Zn retention in the placenta with subsequent reduced transfer to the fetus (Kuhnert et al., 1987, Ronco et al., 2006). It should be noted that MT may be induced by several metals, such as Zn, copper (Cu), Cd and arsenic (As) (Klaassen et al., 1999, Xie et al., 2007). The aim of the present study was to investigate to what extent the accumulation of Cd in human placenta interacts with the transport of various micronutrients (magnesium (Mg), calcium (Ca), manganese (Mn), Cu, Zn, selenium (Se)) to the fetus in non-smoking women in rural Bangladesh. We have previously shown that young pregnant women in this rural area of Bangladesh have elevated body burden of Cd and that malnutrition is prevalent (Kippler et al., 2007, Li et al., 2008). Also, the exposure to As is prevalent due to marked variations in As concentrations in well water (Vahter et al., 2006).
Section snippets
Study area and participants
The study was conducted in Matlab, Bangladesh, where the International Centre for Diarrhoeal Disease Research, Bangladesh (ICDDR,B) is maintaining a Health and Demographic Surveillance System (HDSS) that registers information regarding demography and health of the inhabitants. The HDSS is updated with information collected by community health research workers that perform monthly visits to the families resident in the coverage area of ICDDR,B. In addition, ICDDR,B is running a central hospital
Results
The maternal and infant characteristics are described in Table 1. The mean age of the women was 28 years (range 22–36) and none of them smoked. There were no nulliparous women (with no previous children), as this was a follow-up study of the MINIMat trial conducted in pregnant women. The mean gestational age was 39 weeks and 9% of the infants were born pre-term (<37 weeks). Fifty-three percent of the infants were boys. The mean birth weight was 2821 g and 12% of the infants had a low birth
Discussion
The placenta serves as an interface between fetal and maternal circulation and mediates exchange of gases, as well as transport of nutrients and waste products. The present study is the first to show that elevated Cd concentrations in placenta are associated with impaired Zn transfer to the fetus, which is likely to affect fetal growth and development. Indeed, the results indicated a negative association between placenta Cd and birth weight. The average Cd concentration in umbilical cord blood
Conflict of interest statement
The authors declare that there are no conflicts of interest.
Acknowledgements
The present research study is part of the MINIMat study and was funded by the Swedish International Development Cooperation Agency (Sida) [SWE-2003-021A] and EU through its Sixth Framework Programme for RTD [contract no. FOOD-CT-2006-016253]. It reflects only the authors’ views. The European Community is not liable for any use that may be made of the information contained therein. The MINIMat research study was funded by UNICEF, Sida, UK Medical Research Council, Swedish Research Council,
References (55)
- et al.
Maternal and umbilical cord blood levels of mercury, lead, cadmium, and essential trace elements in Arctic Canada
Environ. Res.
(2006) - et al.
A piglet model for studies of gastrointestinal uptake of cadmium in neonates
Toxicol. Lett.
(2004) - et al.
The relationship between cadmium and lead burdens and preterm labor
Int. J. Gynecol. Obstet.
(1993) - et al.
Expression of ZnT-1 (Slc30a1) and MT-1 (Mt1) in the conceptus of cadmium treated mice
Reprod. Toxicol.
(2007) - et al.
Cadmium levels in maternal, cord and newborn blood in Mexico City
Toxicol. Lett.
(1997) - et al.
Iron and copper interactions in development and the effect on pregnancy outcome
J. Nutr.
(2003) - et al.
Human placenta as a ‘dual’ biomarker for monitoring fetal and maternal environment with special reference to potentially toxic trace elements. Part 3. Toxic trace elements in placenta and placenta as a biomarker for these elements
Sci. Tot. Environ.
(2001) Mechanisms of cadmium carcinogenesis
Toxicol. Appl. Pharmacol.
(2009)- et al.
Accumulation of cadmium, zinc, and copper in maternal blood and developmental placental tissue: differences between Finland, Estonia, and St. Petersburg
Environ. Res.
(2000) - et al.
Influence of iron and zinc status on cadmium accumulation in Bangladeshi women
Toxicol. Appl. Pharmacol.
(2007)
Factors influencing intestinal cadmium uptake in pregnant Bangladeshi women—a prospective cohort study
Environ. Res.
Cadmium interacts with the transport of essential micronutrients in the mammary gland—A study in rural Bangladeshi women
Toxicology
Lead and cadmium concentrations in maternal and umbilical cord blood, amniotic fluid, placenta, and amniotic membranes
Am. J. Obstet. Gynecol.
The effect of smoking on placental and fetal zinc status
Am. J. Obstet. Gynecol.
A novel duodenal iron-regulated transporter, IREG1, implicated in the basolateral transfer of iron to the circulation
Mol. Cell
Effect of oxidative stress on birth sizes: consideration of window from mid pregnancy to delivery
Placenta
Toxic and essential elements in placentas of Swedish women
Clin. Biochem.
Placental cadmium and progesterone concentrations in cigarette smokers
Reprod. Toxicol.
Smoking specifically induces metallothionein-2 isoform in human placenta at term
Toxicology
The effects of air pollution and smoking on placental cadmium, zinc concentration and metallothionein expression
Toxicology
Environmental exposure to cadmium, forearm bone density, and risk of fractures: prospective population study. Public Health and Environmental Exposure to Cadmium (PheeCad) Study Group
Lancet
DMT1 gene expression and cadmium absorption in human absorptive enterocytes
Toxicol. Lett.
Increased biological oxidation and reduced anti-oxidant enzyme activity in pre-eclamptic placentae
Placenta
Toxicity of cadmium in the perfused human placenta
Toxicol. Appl. Pharmacol.
Aberrant DNA methylation and gene expression in livers of newborn mice transplacentally exposed to a hepatocarcinogenic dose of inorganic arsenic
Toxicology
Effects of zinc, copper, and selenium on placental cadmium transport
Biol. Trace Elem. Res.
Cadmium-induced effects on bone in a population-based study of women
Environ. Health Perspect.
Cited by (184)
Toxic metals and essential trace elements in placenta and their relation to placental function
2024, Environmental ResearchPotential pathological mechanisms and pharmacological interventions for cadmium-induced miscarriage
2024, Ecotoxicology and Environmental SafetyAssociations of micronutrients exposure with cadmium body burden among population: A systematic review
2023, Ecotoxicology and Environmental Safety