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Title: Trophectoderm stem cells to model the effect of altered periconceptional diet on embryos
Author: Chang, Yi-Lung
ISNI:       0000 0004 7234 1912
Awarding Body: University of Southampton
Current Institution: University of Southampton
Date of Award: 2017
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The developmental origin of adult disease hypothesis was presented by David Barker in the late 1980s. He and his colleagues found babies with low birth weight are at a higher risk of cardiovascular disease (Barker and Osmond, 1986) and type II diabetes (Hales et al., 1991) in their adult life. He hypothesized that the gestation environment would affect the offspring in the long term. Animal models also demonstrate the effect of maternal diet on the risk of hypertension, cardiovascular and metabolic disease in the offspring, and on the function of extraembryonic tissue; for example, a maternal low protein diet increased the endocytic capacity of the visceral yolk sac (VYSE) (Watkins et al., 2008). Previous studies show that changing the maternal diet during the pre-implantation period (Day 0 to 3.5) also has long term effects on murine offspring, such as lung and serum angiotensin-converting enzyme (ACE) activity changes (Watkins et al., 2010). During pregnancy, the placenta plays the main role of exchanging nutrients and metabolic products between the foetus and mother, and directly affects the development of the foetus. In this study, a number of parameters changing the ability to isolate TS cell lines were first examined, and we produced recombinant protein FGF4 for TS cell culture. In order to establish an in vitro model to understand how the maternal diet altered inheritable characteristics. TS cell lines were established from low protein (LPD) and normal protein diet (NPD) embryos. These lines were analysed for the expression of TE markers and were characterised for sex and chromosomal stability. Comparing their expression of specific markers of TE differentiation showed that the lines showed great variability in their differentiation pathways. However, despite this the proliferation rate and metabolism as measured by MTT conversion is significantly higher in LPD group. This finding correlated with pervious study, that LPD embryos show a greater number TE cells in the late blastocyst (Eckert et al., 2012). The cell endocytosis activity shown by uptake and conversion of the late endosome marker pHrodo was also increased in our LPD models.
Supervisor: Smyth, Neil Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available