Obesity is a global health problem and the current available evidence from the literature suggests that obese women may suffer from a wide spectrum of reproductive complications. The current understanding of obesogenic effects on the peri-implantation endometrium is limited and has become an important research topic as the emerging clinical evidence from the published studies indicate the possible role of the endometrium. The first part of this thesis addresses the clinical question of whether an early pregnancy outcome is affected by the body mass index and whether there is any difference in time taken to achieve pregnancy in obese women with recurrent miscarriage when compared to normal weight women. The results are in chapters 3 and 4, where we demonstrated that obese women were more likely to have miscarriage of empty gestational sac or anembryonic pregnancies. In recurrent miscarriage context, the obese women were more ‘super-fertile’ suggesting the possible loss of an endometrial ability to select normal from abnormal pregnancies. The second part of this thesis provides an analysis of the peri-implantation endometrial stromal compartment in normal weight and obese women. In chapter 5, using immunohistochemical methods it was shown that there was no difference in the uterine natural killer cell and macrophage density in the peri-implantation endometrium of different weight groups. This suggests that the endometrial dysfunction in obese women with reproductive failure does not appear to be immune cell mediated. In chapter 6 it was shown that the clonogenecity of endometrial mesenchymal stem cells (W5C5+) was significantly negatively correlated with the BMI. The obese women had significantly reduced cloning efficiency of W5C5+ cells when compared to normal weight women, suggesting of a possible sub-optimal regenerative capacity of the endometrium in obese women. Finally, chapter 7 showed a potential association between obesogenic environment and impaired stromal cell decidualisation. Using an in-vitro model, it was shown that there was no significant difference in the expression of decidualisation markers (PRL and IGFBP1) in the decidualising endometrial stromal cells from normal weight women when compared to high BMI women. However, when the stromal cells were decidualised in an artificial obesogenic environment, the PRL expression was significantly inhibited in the presence of supernatant from adipose tissue explants of obese women when compared to normal weight women. In summary, the findings from my work have provided an understanding of the peri-implantation endometrium in obese women and evidence to suggest that the endometrial stromal function is possibly facilitated by metabolic influences.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:632923 |
| Date | January 2014 |
| Creators | Bhandari, Harish |
| Publisher | University of Warwick |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://wrap.warwick.ac.uk/65254/ |
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