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Inkster, Amy Michelle

University of British Columbia

Sex differences arise within the first few cell divisions following fertilization, as evidenced by male (XY) and female (XX) conceptuses showing distinct gene expression patterns pre-implantation. Sex differences persist over the course of gestation, culminating in sex-differential incidences of certain pregnancy complications, including fetal growth restriction and preterm birth. In general, phenotypic sex differences arise from the effects of sex chromosomes or steroid hormones. Observable sex differences in human development arise weeks before fetal testosterone production, implicating an important role for the sex chromosomes. Prenatal sex differences likely involve the placenta, a critical organ facilitating fetal growth and development. The extent of molecular sex differences in the placenta and the effects of the placenta on sex differences across gestation remain largely unexplored. Another factor impacting offspring health is gestational exposure to maternal mood disorders and/or selective serotonin reuptake inhibitors (SSRI). These exposures are associated with increased risk of preterm birth, growth and developmental delays, and poor neonatal adaptation. As SSRIs can cross the placenta and the placenta is involved in serotonin metabolism, the molecular consequences of SSRI exposure and maternal depression may be reflected in the placenta at the epigenetic level. In this dissertation, I studied placental DNA methylation with respect to genetic sex, considering sex differences in DNAme on the autosomes, and DNAme-gene expression relationships in the context of placental X-chromosome inactivation (XCI). I also evaluated the application of standard processing and analysis techniques for DNAme data arising from the X and Y chromosomes. Finally, I investigated whether exposure to SSRIs or maternal depression were associated with alterations in the placental DNAme landscape. Through these studies, I contributed to the scientific community’s understanding of prenatal sex differences, prenatal SSRI exposure, and the role that the placental epigenome plays in both.

Text; Dataset

2025-04-30

Attribution-NonCommercial-NoDerivatives 4.0 International

http://hdl.handle.net/2429/87998

Medical Genetics

University of British Columbia

UBCV

http://creativecommons.org/licenses/by-nc-nd/4.0/