Scholarlink

Background <p>Transgender women (transfemales) often undergo gender-affirming hormone therapy (GAHT). However, the testicular impacts of feminising hormones present heterogeneity due to the complexity of testicular regulatory mechanisms.</p> Method <p>In this study, we analyzed approximately 49,385 single-cell transcriptomes from transfemale human testicular tissue, comparing cellular composition with that of cisgender male individuals across a range of ages. Our approach included clustering of cell types, identification of marker genes, pseudotime analysis of germ cells, and comprehensive cell-cell interaction analyses. We employed immunohistochemistry, quantitative real-time PCR, and immunostaining to validate the key molecular signatures identified in the pathways of interest.</p> Results <p>GAHT led to a significant reduction in spermatogenic cells, accompanied by an unexpected increase in Sertoli cell numbers per seminiferous tubule, suggesting disrupted germ cell-Sertoli cell interactions. Molecular analyses revealed upregulation of genes such as Decorin (DCN), Myoglobin (MB), and Beta-2-Microglobulin (B2M) in Sertoli cells, with enrichment in pathways related to cell adhesion, cytokine response, and wnt signaling. Notably, β-catenin was significantly elevated and translocated into the nucleus of Sertoli cells determined by immunostaining analysis. Additionally, collagen fiber infiltration disrupted the testicular microenvironment, further impairing germline-Sertoli cell communication.</p> Conclusion <p>This study provides novel insights into the testicular alterations associated with GAHT in transfemales, particularly highlighting the role of germline-Sertoli cell interactions in testicular injury. Our findings contribute to a deeper understanding of the testicular response to feminizing hormones, offering a foundation for future therapeutic strategies.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Single-cell RNA sequencing uncovers abnormal Sertoli-cell elevation and testicular niche impairment in the transfemales’s testis

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年7月20日

查看全文
  • Jun Yu,
  • Longfei Hu,
  • Huixia Li,
  • Xiaofeng Li,
  • Chaoye Ma,
  • Ting Jiang,
  • Yongxin Liu,
  • Xue Wang,
  • Xia Li,
  • Liandong Zuo,
  • Haocheng Lin,
  • Wenming Xu,
  • Yiwen Zhou,
  • Yang Liu,
  • Hao Chen

摘要

Background

Transgender women (transfemales) often undergo gender-affirming hormone therapy (GAHT). However, the testicular impacts of feminising hormones present heterogeneity due to the complexity of testicular regulatory mechanisms.

Method

In this study, we analyzed approximately 49,385 single-cell transcriptomes from transfemale human testicular tissue, comparing cellular composition with that of cisgender male individuals across a range of ages. Our approach included clustering of cell types, identification of marker genes, pseudotime analysis of germ cells, and comprehensive cell-cell interaction analyses. We employed immunohistochemistry, quantitative real-time PCR, and immunostaining to validate the key molecular signatures identified in the pathways of interest.

Results

GAHT led to a significant reduction in spermatogenic cells, accompanied by an unexpected increase in Sertoli cell numbers per seminiferous tubule, suggesting disrupted germ cell-Sertoli cell interactions. Molecular analyses revealed upregulation of genes such as Decorin (DCN), Myoglobin (MB), and Beta-2-Microglobulin (B2M) in Sertoli cells, with enrichment in pathways related to cell adhesion, cytokine response, and wnt signaling. Notably, β-catenin was significantly elevated and translocated into the nucleus of Sertoli cells determined by immunostaining analysis. Additionally, collagen fiber infiltration disrupted the testicular microenvironment, further impairing germline-Sertoli cell communication.

Conclusion

This study provides novel insights into the testicular alterations associated with GAHT in transfemales, particularly highlighting the role of germline-Sertoli cell interactions in testicular injury. Our findings contribute to a deeper understanding of the testicular response to feminizing hormones, offering a foundation for future therapeutic strategies.