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Title: Pathogenesis and prevention of diabetes-induced embryopathy
Author: McCracken, Jane E.
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 1999
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Established IDDM in the BB/E rat was associated with severe disturbance in the development of the pre-implantation embryo, as indicated by (1) a five fold increase in the number of unfertilised oocytes, (2) a reduced percentage of expanded blastocytes, and (3) a -20% inner cell mass (ICM) cellular deficit in embryos which reached the expanded blastocyst stage. Data obtained from pregnant Diabetes Prone (DP) BB/E rats during the pre-diabetic period (when the maternal metabolic profile was normal), showed that the full complement of IDDM susceptibility genes was not in itself, sufficient to disturb early embryo development and/or give rise to an ICM cell deficit. In addition, experiments involving the transfer of two-cell embryos showed that the oviductal/uterine environment of a Diabetic DP-BB/E recipient could induce not only an ICM deficit but also a TE cell accretion in embryos from Non-Diabetic Diabetes Resistant (DR) BB/E donor rats. However, transfer of two-cell embryos from Diabetic DP- into Non-Diabetic DR-BB/E mothers did not prevent the development of an ICM cellular deficit or a TE cell accretion - implying earlier damage to the germ cells. Greatly improved metabolic control was achieved in Diabetic DP-BB/E rats before and over the period of conception using sustained release insulin implants. This resulted in a reduction in the number of unfertilised oocytes, an increase in the percentage of expanded blastocysts but no change in ICM cellular deficit. A sensitive and accurate quantitative RT-PCR method was developed and used to determine the ratio of bcl-2 (a cell death agonist gene) to bax (a cell death antagonist gene) expression in single blastocysts from Diabetic DP- and Non-Diabetic DR-BB/E rats. Although the bcl-2 to bax ratio was not significantly increased in blastocytes from diabetic rats, these data demonstrate for the first time that bax and bcl-2 mRNA is present in the pre-implantation embryo.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available