Insight into 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced disruption of zebrafish spermatogenesis via single cell RNA-seq.
Insight into 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced disruption of zebrafish spermatogenesis via single cell RNA-seq.
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通过单细胞RNA-seq研究2，3，7，8-四氯二苯并对二恶英诱导的斑马鱼精子发生中断。
DOI：
10.1093/pnasnexus/pgac060
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发表时间：
2022-07
期刊：
影响因子：
--
通讯作者：
Baker, Tracie R.
中科院分区：
文献类型：
--
作者：
Haimbaugh, Alex;Akemann, Camille;Meyer, Danielle;Gurdziel, Katherine;Baker, Tracie R.
2,3,7,8-四氯二苯并-对二恶英 (TCDD) 是一种强效且环境持久的内分泌干扰化学品。我们之前的工作证明了斑马鱼生命早期暴露于 TCDD 的潜在生殖疾病。斑马鱼在发育过程中的两个性分化窗口期（受精后 3 周和 7 周暴露 1 小时）急剧暴露于低环境相关水平的 TCDD (50 pg/mL) 下，随后出现不育，精子数量减少，并且即使在暴露数月后，也表现出与微环境改变一致的基因表达。由于睾丸细胞类型和阶段景观的高度异质性，我们假设不同的细胞类型对 TCDD 暴露的病理学有显着不同的影响。为了研究成年斑马鱼睾丸中不同细胞类型对 TCDD 诱导的病理学的贡献，我们利用单细胞 RNA-seq 和 10x Genomics 平台。该方法成功捕获了睾丸生殖细胞发育的每个阶段。在性分化过程中暴露于 TCDD 的成鱼睾丸中晚期精母细胞、精子细胞和精子的数量急剧减少。相反，精原细胞和早期精母细胞群在暴露后丰富。差异表达基因的通路分析支持了先前的发现，即 TCDD 暴露导致男性不育，并表明这种结果是由于精细胞和精子的凋亡，即使在停止暴露数年后也是如此。组织学证实生殖细胞凋亡增加。这些结果为特发性男性不育症的环境暴露解释提供了支持。
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a potent and environmentally persistent endocrine disrupting chemical. Our previous work demonstrated the latent reproductive maladies of early-life TCDD exposure in zebrafish. Zebrafish acutely exposed to low, environmentally relevant levels of TCDD (50 pg/mL) during two windows of sexual differentiation in development (1 hour of exposure at 3 and 7 weeks postfertilization) were later infertile, showed a reduction in sperm, and exhibited gene expression consistent with an altered microenvironment, even months after exposure. Due to the highly heterogeneous cell- type and -stage landscape of the testes, we hypothesized various cell types contribute markedly different profiles toward the pathology of TCDD exposure. To investigate the contributions of the diverse cell types in the adult zebrafish testes to TCDD-induced pathology, we utilized single-cell RNA-seq and the 10x Genomics platform. The method successfully captured every stage of testicular germ cell development. Testes of adult fish exposed during sexual differentiation to TCDD contained sharply decreased populations of late spermatocytes, spermatids, and spermatozoa. Spermatogonia and early spermatocyte populations were, in contrast, enriched following exposure. Pathway analysis of differentially expressed genes supported previous findings that TCDD exposure resulted in male infertility, and suggested this outcome is due to apoptosis of spermatids and spermatozoa, even years after exposure cessation. Increased germ cell apoptosis was confirmed histologically. These results provide support for an environmental exposure explanation of idiopathic male infertility.
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斑马鱼中疾病的跨代遗传的二恶英诱导。
影响因子：
4.1
作者：
Baker TR;King-Heiden TC;Peterson RE;Heideman W
通讯作者：
Heideman W
影响因子：
44.1
作者：
Guo J;Grow EJ;Mlcochova H;Maher GJ;Lindskog C;Nie X;Guo Y;Takei Y;Yun J;Cai L;Kim R;Carrell DT;Goriely A;Hotaling JM;Cairns BR
通讯作者：
Cairns BR
影响因子：
11.8
作者：
Green CD;Ma Q;Manske GL;Shami AN;Zheng X;Marini S;Moritz L;Sultan C;Gurczynski SJ;Moore BB;Tallquist MD;Li JZ;Hammoud SS
通讯作者：
Hammoud SS
影响因子：
1.9
作者：
Dhanabalan, S.;Mathur, P. P.;Latha, P.
通讯作者：
Latha, P.
影响因子：
10.5
作者：
Cabili, Moran N.;Trapnell, Cole;Rinn, John L.
通讯作者：
Rinn, John L.