Project: Mechanisms of metal toxicity early in life

We study mechanisms of metal toxicity, where we focus mainly on oxidative stress, epigenetic alterations, and hormone-related effects, following early-life exposure. Many toxic metals, such as arsenic, cadmium, and lead, have been shown to be potent inducers of oxidative stress. Epigenetic alterations may explain why early-life exposure to metals, especially prenatally, seems to cause diseases later in life. Moreover, it has been suggested that several metals can cause endocrine disruption. For example, experimental studies have suggested that cadmium can interact with both estrogens and androgens, but if cadmium can affect the hormone systems, which are crucial for early in life development, remains to be elucidated. The placenta is the key mediator as it receives and transmits endocrine signals between the mother and her fetus. Cadmium accumulates in the placenta during pregnancy with only a small fraction passing over to the fetus. Our hypothesis is that this disrupts hormonal signaling between the mother and her fetus, which may results in impaired fetal growth and neurodevelopment during childhood. We are currently focusing on three hormonal systems – glucocorticoids, insulin-like growth factors (IGFs), and thyroid hormones (THs), all of which are fundamental for normal fetal development. The studies are mainly done using placental tissue collected within the mother-child cohorts in Bangladesh and Argentina, in combination with in vitro studies. We are also conducting epidemiological studies where we measure the children’s prenatal and concurrent toxic exposures and the above mentioned hormones in urine or plasma.

Contact persons

Maria Kippler and Annachiara Malin Igra


  • Swedish research Council
  • Swedish research Council Formas
  • Karolinska Institutet

Selected publications

Sex-specific effects of early life cadmium exposure on DNA methylation and implications for birth weight.
Kippler M, Engström K, Mlakar S, Bottai M, Ahmed S, Hossain M, et al
Epigenetics 2013 May;8(5):494-503

Prenatal lead exposure is associated with decreased cord blood DNA methylation of the glycoprotein VI gene involved in platelet activation and thrombus formation.
Engström K, Rydbeck F, Kippler M, Wojdacz T, El Arifeen S, Vahter M, Broberg K. 2016.
Accepted in Environ Epigenetics.

Exposure to lithium through drinking water and calcium homeostasis during pregnancy: A longitudinal study.
Harari F, Åkesson A, Casimiro E, Lu Y, Vahter M
Environ. Res. 2016 May;147():1-7

Exposure to Lithium and Cesium Through Drinking Water and Thyroid Function During Pregnancy: A Prospective Cohort Study.
Harari F, Bottai M, Casimiro E, Palm B, Vahter M
Thyroid 2015 Nov;25(11):1199-208

Arsenic Metabolism in Children Differs From That in Adults.
Skröder Löveborn H, Kippler M, Lu Y, Ahmed S, Kuehnelt D, Raqib R, et al
Toxicol. Sci. 2016 07;152(1):29-39

Early life low-level cadmium exposure is positively associated with increased oxidative stress.
Kippler M, Hossain M, Lindh C, Moore S, Kabir I, Vahter M, et al
Environ. Res. 2012 Jan;112():164-70