Repeated sampling facilitates within- and between-subject modeling of the human sperm transcriptome to identify dynamic and stress-responsive sncRNAs.
Repeated sampling facilitates within- and between-subject modeling of the human sperm transcriptome to identify dynamic and stress-responsive sncRNAs.
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DOI：
10.1038/s41598-020-73867-7
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发表时间：
2020-10-15
影响因子：
4.6
通讯作者：
Bale TL
中科院分区：
文献类型：
--
作者：
Morgan CP;Shetty AC;Chan JC;Berger DS;Ament SA;Epperson CN;Bale TL
上世纪的流行病学研究表明，父亲的生活经历与后代的健康和疾病结果之间存在密切的联系。最近的研究表明，精子小非编码 RNA (sncRNA) 群体对不同的父亲侮辱的反应有所不同。然而，对于回顾性或前瞻性人类队列研究，以确定父系生殖细胞表观遗传学变化与后代疾病风险相关的变化，必须首先建立一个框架，深入了解人类群体固有的预期生物变异。换句话说，如果我们不首先知道什么是稳定的，什么是动态的，以及随着时间的推移，什么是在人内部和人之间保持一致的，我们怎么知道要寻找什么？在 6 个月内重复从每个受试者身上收集的“标准”健康人类受试者队列的精子样本中，17 名健康男性参与者符合纳入标准，并每月完成捐赠和感知压力的心理评估。从这些样本的成熟精子中分离出的 sncRNA（包括 miRNA、piRNA 和 tRNA）经过 Illumina 小 RNA 测序，与亚型特异性参考转录组进行比对并进行定量。重复测量设计使我们能够定义精子中 254 个 miRNA、194 个 tRNA 和 937 个 piRNA 表达随时间的变化。我们制定了筛选标准来识别潜在的环境响应“动态”精子 sncRNA 的子集。通过对这些数据中的个体动态 sncRNA 和感知压力状态之间的关系进行复杂的建模，我们确定了 5 种 miRNA（包括 let-7f-5p 和 miR-181a-5p）和 4 种 tRNA，它们对先前压力经历的动态做出响应并适合我们建立的小鼠模型。在当前的研究中，我们将人类精子 sncRNA 表达数据的重复采样与感知压力的同步测量结合起来，作为一个新的框架，现在可以应用于一系列专注于能够影响生殖细胞编程并可能影响后代发育的不同环境因素的研究。
Epidemiological studies from the last century have drawn strong associations between paternal life experiences and offspring health and disease outcomes. Recent studies have demonstrated sperm small non-coding RNA (sncRNA) populations vary in response to diverse paternal insults. However, for studies in retrospective or prospective human cohorts to identify changes in paternal germ cell epigenetics in association with offspring disease risk, a framework must first be built with insight into the expected biological variation inherent in human populations. In other words, how will we know what to look for if we don’t first know what is stable and what is dynamic, and what is consistent within and between men over time? From sperm samples from a ‘normative’ cohort of healthy human subjects collected repeatedly from each subject over 6 months, 17 healthy male participants met inclusion criteria and completed donations and psychological evaluations of perceived stress monthly. sncRNAs (including miRNA, piRNA, and tRNA) isolated from mature sperm from these samples were subjected to Illumina small RNA sequencing, aligned to subtype-specific reference transcriptomes, and quantified. The repeated measures design allowed us to define both within- and between-subject variation in the expression of 254 miRNA, 194 tRNA, and 937 piRNA in sperm over time. We developed screening criteria to identify a subset of potential environmentally responsive ‘dynamic’ sperm sncRNA. Implementing complex modeling of the relationships between individual dynamic sncRNA and perceived stress states in these data, we identified 5 miRNA (including let-7f-5p and miR-181a-5p) and 4 tRNA that are responsive to the dynamics of prior stress experience and fit our established mouse model. In the current study, we aligned repeated sampling of human sperm sncRNA expression data with concurrent measures of perceived stress as a novel framework that can now be applied across a range of studies focused on diverse environmental factors able to influence germ cell programming and potentially impact offspring development.
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影响因子：
64.5
作者：
Ashe A;Sapetschnig A;Weick EM;Mitchell J;Bagijn MP;Cording AC;Doebley AL;Goldstein LD;Lehrbach NJ;Le Pen J;Pintacuda G;Sakaguchi A;Sarkies P;Ahmed S;Miska EA
通讯作者：
Miska EA
影响因子：
5
作者：
COHEN, S;KAMARCK, T;MERMELSTEIN, R
通讯作者：
MERMELSTEIN, R
影响因子：
14.9
作者：
Chan PP;Lowe TM
通讯作者：
Lowe TM
影响因子：
11.3
作者：
Ahrnberg, Hanna;Pajulo, Marjukka;Karukivi, Max
通讯作者：
Karukivi, Max
影响因子：
10.6
作者：
Chan JC;Nugent BM;Bale TL
通讯作者：
Bale TL