The Effect of Aberrant Inflammation During Pregnancy on Subsequent Risk of Maternal Metabolic Disease Development

Inflammatory pregnancy complications are linked to an increased development of metabolic disease in mothers and their offspring. Previous studies from our lab have shown the development of risk factors for disease development following pregnancy complications. It is thought that pregnancy complications prime the maternal immune system to mount an increased response to a secondary source of inflammation, such as a high fat diet (HFD). This led to the hypothesis that an inflammatory pregnancy complication followed by a HFD leads to the increased development of maternal metabolic disease. Also, that exposure to inflammation in utero followed by a HFD results in development of metabolic disease in growth restricted offspring. To study maternal metabolic disease development, bacterial lipopolysaccharide (LPS) was administered to induce inflammation to pregnant mice on gestational day (GD) 10.5, resulting in total fetal loss. Starting on GD 24.5, the mice consumed a HFD for 10 weeks, being weighed every 2-3 days. Mice were then given an intraperitoneal glucose tolerance test (IPGTT) to assess glucose metabolism. Following this, the liver and pancreas were collected to assess various parameters of metabolic disease. Plasma concentration of various adipokines were also measured. Overall, the results of this study did not support the hypothesis, as the animals who experienced a non-inflammatory pregnancy followed by a HFD exhibited the highest instances of metabolic disease development. This was shown via impaired glucose metabolism, significant weight gain, increased fatty liver, and elevated plasma concentrations of the adipokines PAI-1 and leptin. In terms of the offspring, inflammation was induced in pregnant rats on GD 13.5-16.5 via LPS to induce fetal growth restriction. After weening, the offspring were placed on a HFD for 16 weeks, being weighed every 3 days. IPGTTs were completed to observe glucose metabolism. The male offspring who did not experience inflammation in utero and were fed a HFD had the most significant alterations to glucose metabolism, suggesting the development of insulin resistance. While neither hypotheses were proven, this study showed that a non-inflammatory pregnancy followed by a HFD can result in increased metabolic disease development when compared to pregnancy alone or solely consuming a HFD.

Department dc:contributor.department

Biomedical and Molecular Sciences

Year dc:date.issued

2024

Author dc:creator

• Fava, Gabrielle

Advisor dc:contributor.supervisor

• Graham, Charles

• Reproduction and Development
• Metabolic Disease
• Women's Health
• Developmental Origins of Health and Disease
• Innate Immune Reprogramming

Statement dc:rights

• Attribution-NonCommercial-NoDerivatives 4.0 International

Licence dc:rights.uri

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

Language dc:language.iso

eng

Handle dc:identifier.uri

https://hdl.handle.net/1974/33232

OAI identifier oai:identifier

oai:queensu.scholaris.ca:1974/33232