Transcriptional networks underlying a primary ovarian insufficiency disorder in alligators naturally exposed to EDCs
Transcriptional networks underlying a primary ovarian insufficiency disorder in alligators naturally exposed to EDCs
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DOI：
10.1016/j.mce.2022.111751
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发表时间：
2022-08-13
影响因子：
4.1
通讯作者：
Parrott，Benjamin B.
中科院分区：
文献类型：
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作者：
Hale，Matthew D.;Koal，Therese;Parrott，Benjamin B.
内分泌系统和环境污染物之间的相互作用是损害生殖发育和功能的原因。尽管受影响物种的分类多样性和自然系统固有的复杂性，但基本的信号通路和细胞后果主要在实验室模型中研究。要解决的遗传和内分泌途径，介导受影响的卵巢功能的有机体暴露于内分泌干扰物在其自然环境中，我们评估了大规模的转录和类固醇激素的反应，外源性促性腺激素刺激的少年短吻鳄（短吻鳄密西西比）起源于一个湖泊，有充分的记录污染（湖Apopka，佛罗里达州）和附近的参考网站（湖伍德拉夫，佛罗里达州）。我们发现，从Apopka湖的个人的特点是高雄激素血症和显示超敏感的促性腺激素刺激的转录反应相比，从伍德拉夫湖的个人。位点特异性转录组分化似乎是由完全不同的转录调节子亚群驱动的，表明卵巢功能的基本遗传途径发生了改变。与广泛的转录差异一致，Apopka湖短吻鳄的卵巢显示卵泡发育障碍，具有较大的germinal床和后期卵泡数量减少。在将卵巢转录组分解为共表达基因簇后，大多数位点相关模块与个体间的卵泡表型相关。然而，两个位点特异性簇的表达独立于卵巢细胞结构，并假设代表细胞自主转录程序的改变。总的来说，我们的研究结果提供了高分辨率的转录模式映射到特定的生殖功能，并推进我们对环境内分泌干扰的既定模型中生殖健康受损的机械理解。
Interactions between the endocrine system and environmental contaminants are responsible for impairing reproductive development and function. Despite the taxonomic diversity of affected species and attendant complexity inherent to natural systems, the underlying signaling pathways and cellular consequences are mostly studied in lab models. To resolve the genetic and endocrine pathways that mediate affected ovarian function in organisms exposed to endocrine disrupting contaminants in their natural environments, we assessed broad-scale transcriptional and steroidogenic responses to exogenous gonadotropin stimulation in juvenile alligators (Alligator missippiensis) originating from a lake with well-documented pollution (Lake Apopka, FL) and a nearby reference site (Lake Woodruff, FL). We found that individuals from Lake Apopka are characterized by hyperandrogenism and display hyper-sensitive transcriptional responses to gonadotropin stimulation when compared to individuals from Lake Woodruff. Site-specific transcriptomic divergence appears to be driven by wholly distinct subsets of transcriptional regulators, indicating alterations to fundamental genetic pathways governing ovarian function. Consistent with broad-scale transcriptional differences, ovaries of Lake Apopka alligators displayed impediments to folliculogenesis, with larger germinal beds and decreased numbers of late-stage follicles. After resolving the ovarian transcriptome into clusters of co-expressed genes, most site-associated modules were correlated to ovarian follicule phenotypes across individuals. However, expression of two site-specific clusters were independent of ovarian cellular architecture and are hypothesized to represent alterations to cell-autonomous transcriptional programs. Collectively, our findings provide high resolution mapping of transcriptional patterns to specific reproductive function and advance our mechanistic understanding regarding impaired reproductive health in an established model of environmental endocrine disruption.