| First Author | Selvaratnam J | Year | 2013 |
| Journal | Am J Physiol Endocrinol Metab | Volume | 305 |
| Issue | 6 | Pages | E727-35 |
| PubMed ID | 23880315 | Mgi Jnum | J:202704 |
| Mgi Id | MGI:5521250 | Doi | 10.1152/ajpendo.00157.2013 |
| Citation | Selvaratnam J, et al. (2013) Metallothionein-I- and -II-deficient mice display increased susceptibility to cadmium-induced fetal growth restriction. Am J Physiol Endocrinol Metab 305(6):E727-35 |
| abstractText | Maternal cadmium exposure induces fetal growth restriction (FGR), but the underlying mechanisms remain largely unknown. The placenta is the main organ known to protect the fetus from environmental toxins such as cadmium. In this study, we examine the role of the two key placental factors in cadmium-induced FGR. The first is placental enzyme 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2), which is known to protect the fetus from exposure to high cortisol levels and subsequently FGR, and the second the cadmium binding/sequestering proteins metallotheionein (MT)-I and -II. Using the MT-I/II(-/-) mouse model, pregnant mice were administered cadmium, following which pups and placentas were collected and examined. MT-I/II(-/-) pups exposed to cadmium were significantly growth restricted, but neither placental weight nor 11beta-HSD2 was altered. Although cadmium administration did not result in any visible structural changes in the placenta, increased apoptosis was detected in MT-I/II(-/-) placentas following cadmium exposure, with a significant increase in levels of both p53 and caspase 3 proteins. Additionally, glucose transporter (GLUT1) was significantly reduced in MT-I/II(-/-) placentas of pups exposed to cadmium, whereas zinc transporter (ZnT-1) remained unaltered. Taken together, these results demonstrate that MT-I/II(-/-) mice are more vulnerable to cadmium-induced FGR. The present data also suggest that increased apoptosis and reduced GLUT1 expression in the placenta contribute to the molecular mechanisms underlying cadmium-induced FGR. |
