Abstract

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 (${\mathrm{E}}_2$) 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 ${\mathrm{E}}_2$-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 ${\mathrm{E}}_2$ 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 ${\mathrm{E}}_2$ 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. https://doi.org/10.1289/EHP6627

中文翻译：

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评估发育早熟的雌激素信号传导能力以概括污染湖中鳄鱼的卵巢转录组和卵泡动力学的能力。

摘要

背景：

在最近的几十年中，对人为干扰室内分泌激素功能的污染物的关注日益增加。但是，在自然暴露的人群中，对于将发育过程与与内分泌干扰化学物质（EDC）暴露相关的病理学联系起来的机制了解甚少。

目标：

我们力求a）表征源自历史上曾被EDC污染的地点，阿波普卡湖和参考地点的扬子鳄在卵巢转录组和卵泡形态方面的差异；b）测试发育早熟的雌激素暴露的能力，以概括与部位相关的发散模式；和Ç用外源性促卵泡激素（FSH治疗））测试是否能够挽救与污染物暴露和/或胚胎雌激素治疗相关的表型的。

方法：

从污染地点和参考地点收集扬子鳄卵，用雌二醇处理来自参考地点的一部分卵（${\mathrm{Ë}}_2$）在性腺分化之前的胚胎发育过程中。孵化后，将扬子鳄在受控的实验室环境中饲养5个月。将两个地点的少年分开，并用外源性FSH治疗。进行组织学分析和RNA测序，以表征位点之间，参考位点与参考位点之间卵巢卵泡动力学和转录组的差异。${\mathrm{Ë}}_2$-处理的动物，以及FSH-处理的动物和未处理的动物之间。

结果：

我们观察到了来自卵巢转录组的广泛原点分歧，以及来自阿波普卡湖的扬子鳄与参考点之间的卵泡密度降低。从参考部位治疗胚胎${\mathrm{Ë}}_2$在Apopka湖中发现了绝大多数的转录和组织学变化。通过外源性FSH治疗只能部分挽救在阿波普卡湖扬子鳄中观察到的或由雌激素治疗引起的卵巢表型。

讨论：

通过性早熟概述卵巢异常 ${\mathrm{Ë}}_2$在环境内分泌破坏的历史例子中，揭示了一种相对简单的机制，其是由污染物引起的病理学的基础。此处报道的发现支持一种模型，其中雌激素信号的发育时机有可能永久改变卵巢的组织和功能。https://doi.org/10.1289/EHP6627