Master of Science
Meredith Protas, PhD
Joseph Chen, PhD
Keith Abe, PhD
Galactosemia is a rare, debilitating metabolic disorder whereby the body cannot effectively metabolize galactose. It is caused by an inherited autosomal recessive mutation in the gene coding for galactose-1 phosphate uridyltransferase (GALT), resulting in a toxic build-up of galactose and its metabolite Gal-1P in various organs. Newborns are diagnosed based on circulating galactose and GALT enzyme activity in the blood, and subsequently put onto a lactose/galactose-free diet. However, galactose accumulation can still occur due to endogenous production in the body, leading to pathologies including premature ovarian failure (POF) in women. Several animal models for galactosemia exist, but it is not known if these models present with POF. The objective of this thesis work was to identify two markers of healthy ovarian follicles, anti-müllerian hormone (AMH) and mouse vasa homolog (MVH), in aging female rodent models, to characterize normal POF progression. Additionally, two rodent models of galactosemia were utilized to elucidate possible changes in ovarian markers of POF: a mouse and a rat model. A histological-based immunohistochemistry (IHC) assay and an Enzyme Linked Immunosorbent Assay (ELISA) were used to measure the expression of ovarian AMH and MVH in control and aging wild type (WT) mice, to show the age-dependent decrease in these markers. AMH and MVH were detectable at 4 weeks of age, significantly declined at 24 and 48 weeks of age, and were undetectable at 72 weeks in aging rodent models. In both rodent models of galactosemia, there was a significant age dependent decrease of follicles, but no phenotypic-associated decrease compared to age-matched WT littermates. Together, our results indicate that while AMH and MVH are robust markers of POF in mice and rat models of galactosemia, the phenotypes were not severe enough to affect ovarian expression of these biomarkers. Additional work should be dedicated to creating other models of galactosemia that present with reproductive phenotypes. Our results show the potential of using MVH as a useful and relevant marker of primordial follicles and could be further leveraged in the future to study models of POF.
Available for download on Friday, May 31, 2024