THE MECHANISM OF CADMIUM-INDUCED FETAL GROWTH RESTRICTION: ROLE OF PLACENTAL 11 ß - HYDROXY STEROID DEHYDROGENASE 2 (llß-HSD2) AND METALLOTHIONEIN PROTEINS I & H.
Date of Award
Master of Science
Dr. Kaiping Yang
Dr. James Koropatnick
Dr. Andrew Watson
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.
Selvaratnam, Johanna Samantha, "THE MECHANISM OF CADMIUM-INDUCED FETAL GROWTH RESTRICTION: ROLE OF PLACENTAL 11 ß - HYDROXY STEROID DEHYDROGENASE 2 (llß-HSD2) AND METALLOTHIONEIN PROTEINS I & H." (2009). Digitized Theses. 3976.