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Abstract

Mercury (Hg) is one of the top ten chemicals of major public health concern. The general population is exposed to different levels of Hg through various sources; these usually include exposure to methyl-Hg (MeHg) from seafood intake and Hg0 vapour released from dental amalgams. In contrast to irreversible dysfunctions and anomalies observed in children who were prenatally exposed to high levels of Hg, possible health effects because of prenatal low-level Hg exposure are inconsistent and controversial. Reliable exposure assessment is challenged many times by the lack of Hg speciation and unsuitability of included exposure or susceptibility biomarkers.
The objectives of this work were to show how Hg speciation in blood can contribute to associations between low-level Hg exposure and health effects, whether meconium can be a suitable biomarker of prenatal long-term Hg exposure, and to study Apolipoprotein E (ApoE) ε4 allele as a biomarker of susceptibility. Biological samples were collected from pregnant women and their newborns from Slovenia (N = 584) and Croatia (N = 234) that were life-long exposed to Hg mainly through seafood intake and dental amalgams.
The observed results showed the importance of speciation when assessing Hg exposure and its adverse effects on the general population. Inter-individual differences in exposure to Hg0 or Hg(II) significantly contributed to the variations in proportions of MeHg, which makes measurements of total Hg (THg) an unreliable exposure biomarker. Results showed that the proportion of THg as MeHg in maternal blood and cord blood varied between 4%-100% and 8%-100%, respectively.
Hg speciation in meconium showed that Hg(II) presented the majority (82%-100%) of measured THg in the meconium and that high Hg(II) content primarily originates from placental transport of Hg0. Although MeHg from seafood was shown to be transported through the placental barrier, prenatal MeHg biotransformation to Hg(II) could not be confirmed nor excluded. Further studies are needed to confirm these observations.
Statistically significant differences among ApoE ε4 carriers vs. non-carriers were observed. The results showed that mothers who were ε4 carriers had higher levels of plasma Se (ε4 carriers vs. non-carriers: 62.6 and 54.9 ng/mL, respectively). Moreover, children who were ε4 carriers had marginally significant higher cord blood THg levels in comparison with non-carriers, and a Hg-associated decrease in the cognitive score of children who were ε4 carriers was observed. Hg-associated decrease in fine motor skills of children was genotype independent. Further studies are needed to establish the physiological role(s) of ApoE.
In this dissertation the importance of Hg speciation was confirmed. We showed that Hg speciation provides clearer information about blood levels of different Hg species, which can reduce the possibility of misinterpretations when studying metabolism or associations between prenatal low-level Hg exposure and child development. Hg speciation in meconium revealed that meconium can be used as a biomarker of prenatal exposure. Higher plasma Se levels in mothers who were ApoE ε4 carriers could be connected to beneficial effects of ApoE during pregnancy and early life. On the other hand, there is certain evidence that children who are ε4 carriers can be more susceptible to negative effects of Hg, but further research is needed to confirm the latter.