Project Title:

The Impact of Low Dose Methotrexate Exposure During Pregnancy on the Developing Epigenome

Project Summary:

Medication use during pregnancy is tightly regulated to prevent developmental defects in the offspring, however, the effect of commonly prescribed drugs on the developing epigenome is yet to be determined. Methotrexate (MTX) is a commonly prescribed drug that has reported effects of hypomethylation of the genome. Traditional studies exploring MTX exposure during pregnancy have focused on the use of high dose MTX, as used in cancer treatment, and these doses have been defined as teratogenic. However, MTX is increasingly being prescribed at significantly lower doses to treat numerous chronic disorders such as rheumatoid arthritis and Crohn’s disease. Data surrounding the safety of use of low dose MTX in pregnancy and the impact of chronic MTX exposure to the germline is almost non-existent. My project will explore the impact of these lower dose regimens which are commonly prescribed in women of childbearing age to help determine whether MTX can be safely administered during pregnancy.