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<p>Exogenous estrogen (17β-estradiol, E2) induces partial sex reversal in the Chinese giant salamander (CGS) at low concentrations (25&#xa0;µg/L), and complete sex reversal at high concentrations (1000&#xa0;µg/L), suggesting potential risks of skewed sex ratios in wild populations of this critically endangered species. Simultaneously, controlled sex reversal offers a strategy to enhance the aquaculture efficiency of captive CGS. However, the molecular mechanisms underlying this process remain largely unexplored. Here, we generated histological evidence of male-to-female sex reversal in CGS under E2 treatment and characterized dynamic, multi-timepoint transcriptomic changes during this process. Integrating histological and transcriptomic data, we identified 210 days post-hatching (120 days after hormone treatment) as a critical window for male gonadal sex reversal. During this period, E2 upregulates meiosis-related genes, promoting and maintaining the transition from male to female gonads. Concurrently, E2 suppresses <i>DMRT1</i> expression, inhibiting male-specific differentiation pathways and facilitating testicular feminization. Notably, early E2 exposure increases <i>CYP19A</i> expression, but as E2 accumulates, it gradually supplants role of <i>CYP19A</i> in hormone-mediated regulation, resulting in a progressive decline of <i>CYP19A</i> function in gonads. These findings provide a comprehensive molecular and histological framework for understanding E2-induced sex reversal in CGS, offering crucial insights for the conservation of wild populations and for improving aquaculture practices.</p>

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Uncovering the transcriptional landscape of estrogen-induced gonadal feminization in the Chinese giant salamander

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年3月10日

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  • Shijun Yang,
  • Qin Wang,
  • Youyou Li,
  • Yadong Luo,
  • Chao Yang,
  • Yuting Pan,
  • Junyang Zhu,
  • Lishan Xu,
  • Xinlin Wang

摘要

Exogenous estrogen (17β-estradiol, E2) induces partial sex reversal in the Chinese giant salamander (CGS) at low concentrations (25 µg/L), and complete sex reversal at high concentrations (1000 µg/L), suggesting potential risks of skewed sex ratios in wild populations of this critically endangered species. Simultaneously, controlled sex reversal offers a strategy to enhance the aquaculture efficiency of captive CGS. However, the molecular mechanisms underlying this process remain largely unexplored. Here, we generated histological evidence of male-to-female sex reversal in CGS under E2 treatment and characterized dynamic, multi-timepoint transcriptomic changes during this process. Integrating histological and transcriptomic data, we identified 210 days post-hatching (120 days after hormone treatment) as a critical window for male gonadal sex reversal. During this period, E2 upregulates meiosis-related genes, promoting and maintaining the transition from male to female gonads. Concurrently, E2 suppresses DMRT1 expression, inhibiting male-specific differentiation pathways and facilitating testicular feminization. Notably, early E2 exposure increases CYP19A expression, but as E2 accumulates, it gradually supplants role of CYP19A in hormone-mediated regulation, resulting in a progressive decline of CYP19A function in gonads. These findings provide a comprehensive molecular and histological framework for understanding E2-induced sex reversal in CGS, offering crucial insights for the conservation of wild populations and for improving aquaculture practices.