
Meeting Abstract
P1.133 Saturday, Jan. 4 15:30 Receptor Isoform-specific Estrogen Signaling in Müllerian Duct Differentiation of the American Alligator DOHENY, BM*; KOHNO, S; CLOY-MCCOY, JA; GUILLETTE JR, LJ; Medical University of South Carolina; MUSC; MUSC; MUSC bdoheny@gmail.com
Perturbation of endocrine signaling during critical developmental windows has been implicated in adult reproductive disorders. This “developmental origins of disease” paradigm is the basis for our investigation of the role of estrogen signaling in embryonic differentiation of female reproductive tract in the American alligator. To this end, we first investigated pathways leading to sex reversal. Alligator eggs incubated at a temperature that produces 100% males (33.5 °C) were treated with estradiol-17β (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. E2 induced 100% sex reversal, indicated by Müllerian duct presence and gonadal histology. PPT treatment induced 100% gonadal sex reversal and abnormal enlargement of the Müllerian duct. Histological analysis indicated precocious glandular development in these tissues. Quantitative RT-PCR expression assays for steroid hormone receptors revealed significant downregulation of ESR1 and significant upregulation of progesterone receptor in oviductal tissue from PPT treated embryos. Receptor isoform-specific estrogen signaling was further studied by treating embryos incubated at a temperature that produces 100% females (30.5°C) with E2, PPT and ERβ specific agonist WAY 200070. Only PPT treatment induced the previously characterized oviductal phenotype. Further investigation via immunohistochemistry and RT-QPCR continues to reveal significant differences in PPT-treated oviductal tissue. The results of this study provide insight into the factors critical for healthy reproductive system formation in this sentinel species.