Thesis
Metabolomic profiling of the maternal foetal interface and developing foetus during Toxoplasma gondii infection
- Creator
- Rights statement
- Awarding institution
- University of Strathclyde
- Date of award
- 2022
- Thesis identifier
- T16375
- Person Identifier (Local)
- 201779954
- Qualification Level
- Qualification Name
- Department, School or Faculty
- Abstract
- T. gondii infection during pregnancy can cause abortion or congenital disease. Events in the maternal-foetal interface, where immunological changes occur, are critical in determining the pregnancy outcome. Several studies cover the serum biochemical/metabolic changes following T. gondii infection, but limited information exists concerning changes to the placental metabolome or the foetus while in utero. For the first time, this study covers the metabolomic profile and potential underlying mechanisms in the maternal-foetal interface, the developing foetus and maternal serum in BALB/c mice in a T. gondii congenital infection model. Results demonstrate the highest number of metabolite changes in the maternal serum, however a subset of these changes to tryptophan degradation pathway, arginine metabolic pathway was also found in the maternal-foetal interface and the developing foetus. In addition, some metabolites from microbiome origin including indoxylsulfate and 4-guanidinobutanoate were changed compared with the controls, suggesting the potential of T. gondii to change the host microbiome. However, preliminary metagenomics analysis did not demonstrate such changes, albeit in a different model of T. gondii infection. Comparison of alterations of metabolites between the developing foetus and the brain from adult mice born to infected mothers was carried out to determine whether the changes observed in early foetal life were still evident in later life. The most significant finding of this study is that increased kynurenine levels are found in early foetal life. This metabolite was found to be increased in the brains of adult mice with congenital T. gondii infection, but not in uninfected litter mates exposed to maternal-immune activation. This suggests that raised kynurenine levels in foetuses in utero might be maternally derived and short lived, but ultimately endogenously produced in congenitally infected mice. This metabolite has been implicated in psychoneurological diseases, but the consequences of kynurenine exposure in these circumstances remain to be determined.
- Advisor / supervisor
- Roberts, Craig
- Resource Type
- DOI
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PDF of thesis T16375 | 2022-10-24 | 公开 | 下载 |