Author's School

Graduate School of Arts & Sciences

Author's Department/Program

Biology and Biomedical Sciences: Developmental, Regenerative and Stem Cell Biology

Language

English (en)

Date of Award

5-24-2012

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Chair and Committee

Kelle Moley

Abstract

ABSTRACT OF THE DISSERTATION The Importance of Glucose Transport in Reproductive Events by Katie Lynn Adastra Doctor of Philosophy in Biology and Biomedical Sciences Developmental, Regenerative and Stem Cell Biology Washington University in St. Louis, 2012 Professor Kelle H. Moley, Chairperson Successful pregnancy outcome is contingent on a number of factors, the earliest of which include the events occurring during early pregnancy. This time period from fertilization to implantation requires drastic changes in both the embryo and the uterus, including cell proliferation and differentiation. Alterations in environment may lead to adverse effects during any of these stages. This emphasizes the need to understand these early processes and the potential deleterious environments that may be contributing to adverse pregnancy outcome including fetal malformations and demise. In the second chapter, we provide evidence for a differential response of elevated activation of autophagy in embryos and oocytes exposed to a hyperglycemic environment, which is accompanied by an increase in apoptosis. While this environment signaled the activation of these pathways, a hyperglycemic environment during the pre-implantation stage has previously been shown to also alter expression levels of facilitated glucose transporters: SLC2As). One SLC2A in particular, SLC2A8, has been implicated as an important glucose transporter during early pregnancy events, however, a detailed study of this transporter during this time period had been lacking in the literature. Using a Slc2a8 deficient mouse model, the data presented in third chapter is the first to demonstrate that a lack of Slc2a8 leads to reproductive defects most likely due to abnormal decidualization and impaired implantation. This phenotype leads to decreased litter size, and smaller pups at weaning that continue to display an abnormally small growth phenotype into adulthood. In conclusion, the findings in this dissertation support the hypothesis that alterations of the metabolic environment during early pregnancy events can result in aberrations in processes directly impacting fetal outcome and the success of a pregnancy.

Comments

Permanent URL: http://dx.doi.org/10.7936/K7RV0KQ4

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