Estrogen plays a pivotal role in the early stage of sex differentiation in teleost. However, the underlying mechanisms of estrogen-induced feminization process are still needed for further clarification. Here, the comparative analysis of whole-transcriptome RNA sequencing was conducted between 17beta-Estradiol induced feminized XY (E-XY) gonads and control gonads (C) in Takifugu rubripes. A total of 57 miRNAs, 65 lncRNAs, and 4 circRNAs were found to be expressed at lower levels in control-XY (C-XY) than that in control-XX (C-XX), and were up-regulated in XY during E2-induced feminization process. The expression levels of 24 miRNAs, and 55 lncRNAs were higher in C-XY than that in C-XX, and were down-regulated in E2-treated XY. Furthermore, a correlation analysis was performed between miRNA-seq and mRNA-seq data. In C-XX/C-XY, 114 differential expression (DE) miRNAs were predicted to target to 904 differential expression genes (DEGs), while in C-XY/E-XY, 226 DEmiRNAs were predicted to target to 2,048 DEGs. In C-XX/C-XY, and C-XY/E-XY, KEGG pathway enrichment analysis showed that those targeted genes were mainly enriched in MAPK signaling, calcium signaling, steroid hormone biosynthesis and ovarian steroidogenesis pathway. Additionally, the competitive endogenous RNA (ceRNA) regulatory network was constructed by 24 miRNAs, 21 lncRNAs, 4 circRNAs and 5 key sex-related genes. These findings suggested that the expression of critical genes in sex differentiation were altered in E2-treated XY T. rubripes may via the lncRNA-miRNA-mRNA regulation network to facilitate the differentiation and maintenance of ovaries. Our results provide a new insight into the comprehensive understanding of the effects of estrogen signaling pathways on sex differentiation in teleost gonads.

中文翻译：

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非编码 RNA 在调节外源雌激素诱导的红腹鲈性腺女性化中的潜在调节作用


雌激素在硬骨性别分化的早期阶段起关键作用。然而，雌激素诱导的女性化过程的潜在机制仍需要进一步阐明。在这里，在 Takifugu rubripes 中 17β-雌二醇诱导的女性化 XY （E-XY） 性腺和对照性腺 （C） 之间进行了全转录组 RNA 测序的比较分析。共有 57 个 miRNAs、65 个 lncRNAs 和 4 个 circRNAs 在对照 XY （C-XY） 中的表达水平低于对照 XX （C-XX），并且在 E2 诱导的女性化过程中在 XY 中上调。24 个 miRNAs 和 55 个 lncRNAs 在 C-XY 中的表达水平高于 C-XX，在 E2 处理的 XY 中表达水平下调。此外，对 miRNA-seq 和 mRNA-seq 数据进行了相关性分析。在 C-XX/C-XY 中，预测 114 个差异表达 （DE） miRNAs 靶向 904 个差异表达基因 （DEG），而在 C-XY/E-XY 中，预测 226 个 DEmiRNAs 靶向 2,048 个 DEGs。在 C-XX/C-XY 和 C-XY/E-XY 中，KEGG 通路富集分析显示，这些靶向基因主要富集于 MAPK 信号传导、钙信号传导、类固醇激素生物合成和卵巢类固醇生成途径。此外，由 24 个 miRNAs、21 个 lncRNAs、4 个 circRNAs 和 5 个关键性相关基因构建了竞争性内源性 RNA （ceRNA） 调控网络。这些发现表明，在 E2 处理的 XY T. rubripes 中，性别分化中关键基因的表达可能通过 lncRNA-miRNA-mRNA 调节网络发生改变，以促进卵巢的分化和维持。我们的结果为全面理解雌激素信号通路对硬骨性腺性别分化的影响提供了新的见解。