American alligators: integrative wildlife models to explore the developmental origins of health and disease in the environment

The last century of human development has been characterized by the widespread release of chemical contaminants into the environment, many of which can interfere with the endocrine system. Consistent with the developmental origins of health and disease model, embryos are highly sensitive to these endocrine disrupting contaminants (EDCs), and exposures are associated with numerous disease pathologies in adulthood. Despite this, the mechanisms linking developmental EDC exposures to future disease states are not well understood, nor are the consequences of long-term, chronic exposures. Herein, we employ a wildlife model of endocrine disruption, the American alligator, to explore both of these questions.As long-lived predatory species, alligators may receive multi-decadal exposures to contaminants that bioaccumulate/magnify. Leveraging this utility, we use the alligator to explore effects of a toxic EDC, dioxin, in the offspring of exposed individuals inhabiting a historically contaminated system. Using a molecular biomarker of exposure, CYP1A2, we identify contemporary effects of dioxins in embryos, suggesting that offspring of exposed individuals remain susceptible to effects of exposures. We then directly quantify dioxins in alligator egg yolk in this contaminated system and uncover their continued presence decades after initial release.Next, we investigate mechanisms underlying the developmental origins of altered ovarian function, using a population exposed to high levels of organochlorine pesticides (OCPs). Embryos exposed through yolk and raised under lab settings display persistent suppression of fertility-related genes ESR2, AMH, and AHRs, all of which can be recapitulated in reference animals exposed to estradiol prior to gonadal differentiation. These patterns are characteristic of broader changes in the ovary, as non-targeted approaches reveal over 75% of ovarian genes are affected by developmental OCP exposures, the majority of which are recapitulated in estradiol-exposed reference animals. These changes co-occur with altered ovarian follicle profiles, suggesting that OCPs act as estrogens to disrupt follicle development and program future ovarian function, and that the timing of exposures determines future outcomes.Collectively, this work highlights the utility of the alligator as an integrative model to study the effects and mechanisms of development contaminant exposures under environmentally relevant settings.