Grant: Doctoral Award - Frederick Banting and Charles Best Canada Graduate Scholarships

Miscarriage, a loss of pregnancy within the first 3 months, is the most common complication of pregnancy, occurring at a rate of almost 1 in 5. Women with 3 or more miscarriages in a row have recurrent miscarriage, and more than half of cases have no clear cause. The risk of miscarriage increases with age and as women today are increasingly delaying pregnancy this is an important area of research. Sex hormone levels in women change over time and are necessary for eggs to mature properly and for a healthy pregnancy to occur. All hormones are made by genes which differ between individuals by small changes in the sequence that can alter hormone levels. The ends of our DNA are protected by a repetitive sequence known as telomeres that shorten over our lifespan. Short telomeres have been shown to influence pregnancy rate in women. Both of these factors may influence the health of a pregnancy, and therefore be linked to detrimental changes in the placenta, the lifeline for the developing baby. We predict that changes within hormone genes and short telomeres in the mother will increase the risk for recurrent miscarriage, and that these changes will result in abnormal gene regulation in the placenta. DNA from 240 women with recurrent miscarriage and 143 control women have been obtained for this study, in addition to DNA from placental tissue from 120 miscarriages and 30 healthy pregnancies. In this study, changes in the sequences of sex hormone genes essential for female reproduction and telomere lengths will be assessed and compared between women with recurrent miscarriage and controls. Subsequently, chemical changes that regulate the on/off status of genes will be analyzed in placentas from miscarriages and healthy pregnancies. This investigation will help provide a better understanding of recurrent miscarriage. In addition, it may provide clinical tests for identifying contributing factors in some women, leading to better treatment options.