Date of Award

2016

Document Type

Dissertation - MUSC Only

Degree Name

Doctor of Philosophy (PhD)

Department

Molecular and Cellular Biology and Pathobiology

College

College of Graduate Studies

First Advisor

Roger Newman

Second Advisor

John E. Baatz

Third Advisor

Satomi Kohno

Fourth Advisor

John Kucklick

Fifth Advisor

Demetri Spyropoulos

Sixth Advisor

Louis Guilette, Jr.

Abstract

The American alligator represents a multifaceted research model that has potential to inform numerous disciplines ranging from basic developmental biology to ecology and even human reproductive biology. At the root of its utility, however, is a fundamental comprehension of its biology. The overarching goal of the research presented in this dissertation is to clarify our knowledge regarding the molecular responses of the developing alligator reproductive system to environmental signals and then to describe how studies utilizing this model are actively being translated to the setting of human fertility. In chapter one, we set out to identify when the reproductive system of the developing embryo displays thermosensitivity. We employed sensitive thermal shift designs and found that the thermosensitive period for the American alligator initiates by embryonic stage 15 of development, six stages prior than previously reported. We also detected a potential source of intra-sexual phenotypic variation by identifying temperature linked variation in key ovarian promoting transcripts (CYP19A1). We follow this up with experiments described in Chapter 2 aimed at further characterizing the connection between temperature and sex-specific transcript abundance. Together, the reported findings build our knowledge regarding the ability of an environmental factor (temperature) to directly influence the trajectory of sex determination and differentiation in the American alligator. In the final chapters, we expand our analysis from wildlife to the setting of human fertility. We test whether some of the reproductive impairments first noted in contaminant exposed alligators (i.e. impaired ovarian responsiveness) are also relevant to human populations seeking fertility therapy. We focused on an emerging class of environmental contaminants, perfluoroalkyl acids (PFAAs). Our results revealed the presence of six specific PFAAs in the ovarian compartment and identified a negative correlation between one of these compounds (PFUnA) and ovarian responsiveness. The experimental framework described provides an excellent opportunity to explore the potential links between contaminants in the ovarian microenvironment and impaired fertility, a connection that was first hinted at in part by studies of wild alligators in contaminated environment.

Rights

All rights reserved. Copyright is held by the author.

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