de Lima E Martins Lara Nathalia, Jeyhoonabadi Maryam Ahmadi, Dardari Rkia, Elsenhans Anja, Su Lin, Sakib Sadman, Dobrinski Ina
Department of Biochemistry and Molecular Biology, Cumming School of Medicine, and Faculty of Veterinary Medicine, University of Calgary, Calgary, AB, Canada.
Metrology Research Centre, National Research Council Canada, Ottawa, ON, Canada.
Cell Tissue Res. 2025 Aug 21. doi: 10.1007/s00441-025-04004-x.
Mechanisms governing somatic cell interactions in the testis are not well defined. The platelet-derived growth factor (PDGF) pathway mediates epithelial-mesenchymal interactions and is involved in testicular morphogenesis in rodents. However, its roles in the testis of higher mammals remain largely unknown. Here, we investigated how PDGF signaling inhibition affects immature (1-week-old) porcine testicular tubular somatic cells (TTSCs), including cell-cell communication and morphogenesis. From scRNA-seq data, we established the PDGF pathway signatures in crosstalk between testicular cells, identifying Sertoli cells as the primary source and peritubular myoid cells as the main recipients of PDGF. Further, we demonstrated that PDGF inhibition by CP673451 affects TTSC functions, proliferation and cytoskeleton, with reduced cell area, focal adhesion size and fibronectin production, and decreased expression of peritubular myoid cell-specific genes. PDGF inhibition did not impair testicular organoid formation and tubule morphogenesis in vitro, but it correlated with ablation of cytoplasmic extensions from the tubule surface, potentially related to interactions between TTSCs and the extracellular matrix. PDGF signaling can be transduced by primary cilia, sensory organelles that respond to environmental stimuli, and PDGF inhibition increased the percentage of ciliated cells and ciliary length in TTSCs. Comprehensive morphological characterization of primary cilia in the porcine testis indicated that these remain submerged in the cytoplasm. In conclusion, the PDGF signaling pathway is active in the immature pig testis and may influence testis morphogenesis by affecting cell-extracellular matrix interaction, cytoskeleton and primary cilia. However, the role of primary cilia-modulated PDGF signaling in the testis remains to be determined.
睾丸中体细胞相互作用的调控机制尚未明确。血小板衍生生长因子（PDGF）信号通路介导上皮-间充质相互作用，并参与啮齿动物的睾丸形态发生。然而，其在高等哺乳动物睾丸中的作用仍 largely 未知。在此，我们研究了 PDGF 信号抑制如何影响未成熟（1 周龄）猪睾丸管状体细胞（TTSCs），包括细胞间通讯和形态发生。从单细胞 RNA 测序数据中，我们确定了睾丸细胞间串扰中的 PDGF 信号通路特征，确定支持细胞为 PDGF 的主要来源，而睾丸肌样细胞为主要受体。此外，我们证明 CP673451 抑制 PDGF 会影响 TTSC 功能、增殖和细胞骨架，细胞面积、粘着斑大小和纤连蛋白产生减少，以及睾丸肌样细胞特异性基因的表达降低。PDGF 抑制并未损害体外睾丸类器官的形成和小管形态发生，但它与小管表面细胞质延伸的消融相关，这可能与 TTSCs 和细胞外基质之间的相互作用有关。PDGF 信号可由初级纤毛转导，初级纤毛是对环境刺激作出反应的感觉细胞器，PDGF 抑制增加了 TTSCs 中纤毛细胞的百分比和纤毛长度。对猪睾丸中初级纤毛的综合形态学表征表明，这些纤毛仍浸没在细胞质中。总之，PDGF 信号通路在未成熟猪睾丸中活跃，可能通过影响细胞-细胞外基质相互作用、细胞骨架和初级纤毛来影响睾丸形态发生。然而，初级纤毛调节的 PDGF 信号在睾丸中的作用仍有待确定。
