The prevalence of obesity is increasing at an alarming rate. In the UK alone, the majority of adults are overweight or obese, with >60% of men and women falling into this category and >25% being classified as obese. This is highly concerning as in addition to the widely known comorbidities associated with being overweight or obese, maternal or paternal overweight/obesity is linked to reproductive defects, including poor gamete quality and subsequent compromised fertility, pregnancy outcome and offspring health. Despite this, we lack information on the mechanisms linking parental obesity with poor pregnancy outcomes and subsequent offspring disease risk. Furthermore, the specific role of each parent and the combination of both parents being overweight/obese on pregnancy and offspring health has been largely unexplored. This study will endeavour to addess these knowledge gaps by feeding female and male mice a control diet or a high fat diet to induce obesity prior to mating. Different combinations of matings between lean and obese mice will be set up and fetal growth and placental formation and function during gestation will be examined. To identify the extent to which metabolic dysfunction is caused by maternal and / or paternal obesity offspring metabolic health may be determined. Finally, parental oocytes and sperm will be analysed to explore the role of changes in gamete quality and epigenetic status (mRNA, non-coding RNAs, DNA methylation) in the effect of parental obesity on prenatal development and offspring health. Data from parental gametes may be overlaid with transcriptome analyses of the fetus and placenta, to define the parental origin of identified RNAs and to establish the transmission stability from parents to the conceptus. The project will involve will be trained in a variety of in vivo (e.g. placental nutrient transport assays, glucose/insulin tolerance tests, TdNMR scanning) and in vitro (e.g. RNAseq, cytochemistry, stereology, western blotting) techniques and will spend time in both CTR group leader’s lab, to maximise skills training.
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