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Price, Hayley Rose

University of British Columbia

The precise coordination of inflammatory signaling, oxidative stress responses, steroidogenesis, and steroid metabolism are required in all aspects of pregnancy, from fertilization and implantation to parturition. Dysfunction in any of these processes can lead to unfavourable pregnancy outcomes and complications requiring obstetric interventions. As the use of assisted reproductive technologies (ART) has increased in recent decades, it has become evident that these pregnancies are associated with increased risks compared to unassisted pregnancies. However, the underlying reason for these increased risks is unknown. Preliminary studies from our laboratory using a mouse model of ART provide evidence that inflammatory, antioxidant, or steroid pathways could be dysregulated in ART. In this thesis, we investigated the levels inflammatory mediators, measures of antioxidant defense, and steroid hormones in pregnancy to determine any associations with pregnancy outcome. Beginning with an investigation of non- steroidal anti-inflammatory drug (NSAID) use in pregnancy (Chapter 2), we determined the prevalence of NSAID use close to labour. Next, to investigate the differences between ART and unassisted pregnancies, we used a cohort of placentas from ART pregnancies and unassisted pregnancies matched for gestational age, maternal age, ethnicity, and singleton/twin pregnancy. In this cohort, we evaluated the levels of cytokines and vascular endothelial growth factors and identified associations with pregnancy outcome using the accompanying clinical chart profiles (Chapter 3). Further, the activity of antioxidant enzymes and levels of antioxidants were measured in these placentas (Chapter 4). In Chapter 5, we measured the levels of steroid hormones and steroid sulfates in maternal, placental, and fetal compartments, again comparing these results between ART and unassisted pregnancy and identifying associations with pregnancy outcome. No widespread dysregulation of these processes was found between ART and unassisted pregnancies. However, when stratified for pregnancy outcome, two significant associations were found. In pregnancies complicated by chorioamnionitis and in twin pregnancy, there was dysregulation across all three signalling processes. These signalling pathways are complex and interconnected, but the data generated here adds novel findings to the ART field, and identifies potential pathways for future investigation to resolve the etiology of increased pregnancy complications in ART.

Text

2021-12-14

Attribution-NonCommercial-NoDerivatives 4.0 International

http://hdl.handle.net/2429/80435

Pharmaceutical Sciences

University of British Columbia

UBCV

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