Date of Award

2009

Degree Type

Thesis

Degree Name

Master of Science

Program

Physiology

Supervisor

Dr. Kaiping Yang

Second Advisor

Dr. James Koropatnick

Third Advisor

Dr. Andrew Watson

Abstract

Maternal cadmium exposure induces fetal growth restriction (FGR), but the underlying mechanisms remain largely unknown. Placental llß-hydroxysteroid dehydrogenase type 2 (llß-HSD2) has been implicated as a potential molecular target by which cadmium induces FGR. Furthermore, metallothionein-I and II (MT-I/II) sequester cadmium in the placenta, thereby reducing its toxicity on the developing fetus. The present study was undertaken to examine the role of MT- I/II in cadmium-induced FGR using the MT-I/IIA mouse model. Maternal cadmium administration led to FGR and reductions in placental llß- HSD2 activity in MT-I/II1' but not MT-I/lf/+ mice. Although it did not alter placental weight or structure, maternal cadmium administration increased placental cell death in MT-I/lf/+ and MT-I/lf' mice. Together, these results demonstrate that MT-I/II/_ mice are vulnerable to cadmium-induced FGR and reductions in placental llß-HSD2 activity, suggesting that MT-I/II proteins protect the fetus from adverse effects of cadmium on fetal growth and development.

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