Marked developmental changes in heme oxygenase-1 (HO-1) expression in the mouse placenta: correlation between HO-1 expression and placental development.

Heme catabolism during embryonic period is not well understood. It has been suggested that placental heme oxygenase (HO)-1, which is an inducible isoform of the rate-limiting enzyme in the heme degradation pathway, may be involved in supporting normal fetal development. In this study, we examined the distribution of HO-1 protein in the developing mouse embryo, as well as developmental changes of ho-1 gene expression, and the enzyme activity of HO and biliverdin IXalpha reductase (BVR-A) in placenta. Ectoplacental cone in embryonic day (E) 6.5 embryo already showed HO-1 protein expression, which became restricted only to trophoblastic cells after placenta formation was completed on day E14.5. The placenta of E13.5-E14.5 embryos expressed high levels of HO-1 mRNA, which was decreased significantly towards the end of pregnancy. However, HO-1 expression in placenta was significantly higher than uterus throughout the gestational period. In contrast to HO-1, the placental level of BVR-A activity remained low and did not show changes throughout the gestational period. The correlation between HO-1 expression and placental development suggests that HO-1 might be essential for normal embryonic development.