Assessing the Ability of Developmentally Precocious Estrogen Signaling to Recapitulate Ovarian Transcriptomes and Follicle Dynamics in Alligators from a Contaminated Lake

摘要

Background: Concern has grown in recent decades over anthropogenic contaminants that interfere with the functioning of endocrine hormones. However, mechanisms connecting developmental processes to pathologies associated with endocrine-disrupting chemical (EDC) exposure are poorly understood in naturally exposed populations. Objectives: We sought to a ) characterize divergence in ovarian transcriptomic and follicular profiles between alligators originating from a historically EDC-contaminated site, Lake Apopka, and a reference site; b ) test the ability of developmentally precocious estrogen exposure to recapitulate site-associated patterns of divergence; and c ) test whether treatment with exogenous follicle-stimulating hormone (FSH) is capable of rescuing phenotypes associated with contaminant exposure and/or embryonic estrogen treatment. Methods: Alligators eggs were collected from a contaminated site and a reference site, and a subset of eggs from the reference site were treated with estradiol ( E 2 ) during embryonic development prior to gonadal differentiation. After hatching, alligators were raised under controlled laboratory settings for 5 months. Juveniles from both sites were divided and treated with exogenous FSH. Histological analyses and RNA-sequencing were conducted to characterize divergence in ovarian follicle dynamics and transcriptomes between sites, between reference and E 2 -treated animals, and between FSH-treated and nontreated animals. Results: We observed broad site-of-origin divergence in ovarian transcriptomes and reductions in ovarian follicle density between juvenile alligators from Lake Apopka and the reference site. Treating embryos from the reference site with E 2 overwhelmingly recapitulated transcriptional and histological alterations observed in Lake Apopka juveniles. Ovarian phenotypes observed in Lake Apopka alligators or resulting from estrogen treatment were only partially rescued by treatment with exogenous FSH. Discussion: Recapitulation of ovarian abnormalities by precocious E 2 revealed a relatively simple mechanism underlying contaminant-induced pathologies in a historical example of environmental endocrine disruption. Findings reported here support a model where the developmental timing of estrogen signaling has the potential to permanently alter ovarian organization and function.