Maternal obesity is a key predictor of childhood obesity. It has been shown to cause changes in maternal adaptation to pregnancy that result in an adverse in utero environment, inducing increased risk of obesity and metabolic disease in the offspring. Perturbation of gut microbiota over the course of pregnancy has been implicated in maternal metabolic adaptations. We investigated how high-fat (HF) diet-induced obesity before and during pregnancy affects gut microbiota and maternal intestinal barrier function, and whether altered maternal gut adaptations to pregnancy influence placental development. Microbiota of HF mice was modified by diet, and further modulated by pregnancy. Changes in mucin-degrading and short chain fatty acid (SCFA) producing bacteria were found in microbiota from HF pregnant mice. SCFA receptor, GPR41, expression was reduced in the duodenum and jejunum of HF dams. Intestinal barrier function was impaired in HF pregnancies as indicated by increased paracellular intestinal permeability measured by passage of FITC-Dextran and increased concentration of bacterial lipopolysaccharide in the maternal serum, observations that were consistent with reduced gene expression of tight junction proteins in the small intestine of HF dams. Diet-induced maternal obesity altered gene expression of inflammatory and immune cell marker genes in different gut sections. However, no change in TNF and IL-6 in maternal serum suggested that HF diet-induced obesity was not associated with systemic maternal inflammation. Female placenta from HF pregnancies were smaller in size, as calculated by measuring the cross sectional area of the placenta, which may be regulated by increased apoptosis. Augmented placental inflammation was not observed in HF placentas. Changes in maternal intestinal adaptations appear to be modified by diet-induced obesity before and during pregnancy, in a manner that reduced maternal barrier function and increased intestinal immune cell markers but these changes appeared not be associated with placental pro-inflammatory status. / Thesis / Master of Science (MSc)
| Identifer | oai:union.ndltd.org:mcmaster.ca/oai:macsphere.mcmaster.ca:11375/18941 |
| Date | January 2016 |
| Creators | Gohir, Wajiha |
| Contributors | Sloboda, Deborah, Biochemistry and Biomedical Sciences |
| Source Sets | McMaster University |
| Language | English |
| Detected Language | English |
| Type | Thesis |
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