Regulation of CMO1 and CMO2 expression during mouse embryonic development

Abstract

β‐carotene‐15, 15′‐oxygenase (CMO1) and β‐carotene‐9,10′‐oxygenase (CMO2) are the only enzymes known to generate vitamin A from β‐carotene. Both are expressed in mouse and human embryonic and extraembryonic tissues, suggesting a role for β‐carotene as a localized source of vitamin A for developing tissues. Studies indicate that β‐carotene cleavage activity is regulated by nutrient availability in adult tissues. Here we investigate whether nutrient availability may regulate the expression of CMO1 and CMO2 during mouse embryogenesis.Wildtype and CMO1−/− pregnant females were administered β‐carotene by IP injection at 13.5 dpc and sacrificed one day later to collect maternal serum and liver, embryos, yolk sac and placenta. This procedure leads to detectable amounts of β‐carotene in these tissues. Real‐time PCR analysis demonstrated that, in maternal liver, CMO1 expression is down‐regulated while CMO2 is up‐regulated with increasing amounts of β‐carotene. Furthermore, HPLC analysis revealed that administration of β‐carotene also altered maternal serum retinol levels, suggesting the existence of highly regulated mechanisms to ensure that adequate amount of vitamin A are available to the embryo. Experiments are ongoing to analyze the changes in CMO1 and CMO2 expression in embryonic tissues in response to maternal β‐carotene availability and vitamin A status.Grant Funding Source: NIH 5R01HD57493.