SREL Reprint #3858

Embryonic estrogen exposure recapitulates persistent ovarian transcriptional programs in a model of environmental endocrine disruption

Matthew D. Hale1,2, Jessica A. McCoy3, Brenna M. Doheny4, Thomas M. Galligan5, Louis J. Guillette Jr6,7,
and Benjamin B. Parrott1,2

1Savannah River Ecology Laboratory, Aiken, South Carolina, USA
2Odum School of Ecology, University of Georgia, Athens, Georgia, USA
3College of Charleston, Charleston, South Carolina, USA
4School of Public Health, University of Minnesota, Minneapolis, Minnesota, USA
5Department of Fish and Wildlife Conservation, Virginia Tech, Blacksburg, Virginia, USA
6Marine Biomedicine and Environmental Sciences Program, Hollings Marine Laboratory,
Medical University of South Carolina, Charleston, South Carolina, USA
7Department of Obstetrics and Gynecology, Medical University of South Carolina, Charleston, South Carolina, USA

Abstract: Estrogens regulate key aspects of sexual determination and differentiation, and exposure to exogenous estrogens can alter ovarian development. Alligators inhabiting Lake Apopka, FL, are historically exposed to estrogenic endocrine disrupting contaminants and are characterized by a suite of reproductive abnormalities, including altered ovarian gene expression and abated transcriptional responses to follicle stimulating hormone. Here, we test the hypothesis that disrupting estrogen signaling during gonadal differentiation results in persistent alterations to ovarian gene expression that mirror alterations observed in alligators from Lake Apopka. Alligator embryos collected from a reference site lacking environmental contamination were exposed to estradiol-17 beta or a nonaromatizable androgen in ovo and raised to the juvenile stage. Changes in basal and gonadotropin-challenged ovarian gene expression were then compared to Apopka juveniles raised under identical conditions. Assessing basal transcription in untreated reference and Apopka animals revealed a consistent pattern of differential expression of key ovarian genes. For each gene where basal expression differed across sites, in ovo estradiol treatment in reference individuals recapitulated patterns observed in Apopka alligators. Among those genes affected by site and estradiol treatment were three aryl hydrocarbon receptor (AHR) isoforms, suggesting that developmental estrogen signaling might program sensitivity to AHR ligands later in life. Treatment with gonadotropins stimulated strong ovarian transcriptional responses; however, the magnitude of responses was not strongly affected by steroid hormone treatment. Collectively, these findings demonstrate that precocious estrogen signaling in the developing ovary likely underlies altered transcriptional profiles observed in a natural population exposed to endocrine disrupting contaminants.

Keywords: anti-Mullerian hormone, developmental origins of health and disease, differentiation, endocrine disruptors, environment, environmental contaminants and toxicants, estradiol/estradiol receptor, androgens/androgen receptor, follicle-stimulating hormone, gene expression, gonadal function, gonadal steroids, hormone receptors, hormone, ovary, sex differentiation, sex determination, aryl hydrocarbon receptor

SREL Reprint #3858

Hale, M. D., J. A. McCoy, B. M. Doheny, T. M. Galligan, L. J. Guillette Jr., and B. B. Parrott. 2019. Embryonic estrogen exposure recapitulates persistent ovarian transcriptional programs in a model of environmental endocrine disruption. Biology of Reproduction 100(1): 149-161.

This information was provided by the University of Georgia's Savannah River Ecology Laboratory (srel.uga.edu).