Grant: Chair: CIHR Sex and Gender Science Chair - Studying Sex as a Biological Variable

Many differences between males and females arise between conception and birth. As the main regulator of fetal growth and development is the placenta, many of these differences arise because male and female placentas are not equivalent. Male and female placentas differ in their sex chromosome complement, XX vs XY; This leads to sex-chromosome gene expression differences that cause downstream effects on the remainder of the genome. The degree to which male and female placentas differ from each other can also be affected by exposures to fetal and maternal androgens and by genetic variation affecting the expression of key hormones. As such, the effects of sex on the non-sex chromosomes is not discrete, but exists on more of a continuum. Data from DNA methylation, a chemical modification to DNA that is associated with gene expression, has been collected on over 1000 placentas. Our goal is to identify sex-influenced DNA methylation within the placenta, identify the factors that affect this measurement, link this to functional changes in gene expression and determine if the sexual differentiation of the placenta is associated with perinatal outcomes, such and fetal birth weight and gestational age at birth. Ultimately this data could be linked to longer term outcomes in neonates, infants and children. This work is important to understand the early events that set males and females on different health trajectories.