Date of Award

2016

Embargo Period

8-1-2024

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Molecular and Cellular Biology and Pathobiology

College

College of Graduate Studies

First Advisor

Sherine S. L. Chan

Second Advisor

Robert W. Chapman

Third Advisor

Kristi L. Helke

Fourth Advisor

Taisen Iguchi

Fifth Advisor

Satomi Kohmo

Abstract

Perturbation of endocrine signaling during critical embryonic developmental windows has been implicated in many female reproductive system disorders. Reproductive tract anomalies in women exposed in utero to synthetic estrogen diethylstilbestrol, prescribed as a miscarriage preventative, provided some of the first evidence for this “embryonic origins of adult disease” paradigm and suggested a role for estrogen signaling in female reproductive tract (FRT) differentiation. Developmental studies of FRT in other vertebrates have great value in furthering our understanding of embryonic origins of reproductive disorders. The alligator is a particularly intriguing model as an environmental sentinel species with temperature dependent sex determination, which allows for controlled manipulation of sexual differentiation in laboratory experiments. The signals involved in determining regionally specific cell fates in FRT of alligators and other crocodilians are not yet known, but multiple studies in their closest extant evolutionary relative, birds, underscore the role of estrogen signaling in this process. Here I seek to characterize the role of estrogen signaling in the developing alligator FRT. I treated alligator embryos with estradiol-17β (E2) and pharmaceutical agonists that are selective for their two estrogen receptor isoforms, ERα and ERβ. The ERα agonist, propyl pyrazole triol (PPT), induced significant enlargement of the developing FRT, compared with controls and E2 and ERβ agonist treatments. Histological analysis revealed precocious glandulogenesis and connective tissue differentiation similar to mature FRT in these enlarged tissues. PPT treatment also altered expression of steroid hormone receptors and growth factor IGF1. Further experiments assessing this.

Rights

All rights reserved. Copyright is held by the author.

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