Meeting Abstract

P1.92  Wednesday, Jan. 4  Signaling and Timing of Müllerian Duct Differentiation in the American Alligator DOHENY, Brenna M*; KOHNO, Satomi; MCCOY, Jessica A; GUILLETTE JR, Louis J; Medical University of South Carolina, OBGYN/Hollings Marine Laboratory doheny@musc.edu

Perturbation of endocrine signaling during critical developmental windows has been implicated in decreased fertility and reproductive disorders. Using the “developmental origins of disease” paradigm, we examined the differentiation of the Müllerian duct into female reproductive tract structures. Müllerian duct development involves estrogen signaling, and is thus susceptible to disruption via environmental contaminants. The alligator is a useful model for studying reproductive system development, because sex determination is not genetic, but reliant on egg incubation temperature. To identify and characterize critical events in the differentiation of the alligator oviduct, we investigated pathways leading to sex reversal. Alligator eggs incubated at a temperature that produces 100% males (33.5 C) were treated with estradiol-17beta (E2) or 4,4',4''-(4-Propyl-[1H]-pyrazole-1,3,5
-triyl)trisphenol (PPT), a specific agonist for estrogen receptor alpha (ERα), at a stage just prior to sex determination. In an initial study, E2 induced 100% sex reversal, indicated by Mülllerian duct presence. PPT treatment induced sex reversal and Müllerian duct hyperplasia. Our current study examines the timing of signaling cascades by which increased ERα activity induces sex reversal. Müllerian duct tissue from different time points during sex determination was analyzed histologically, and by expression assays using quantitative RT-PCR for genes involved in temperature-dependent sex determination and expected to be regulated through ERα. The results of this study provide a model of normal ovarian and oviduct development, which is key to understanding developmental factors critical in the formation of a healthy reproductive system.