Errico Andrea, Ambrosini Giulia, Vinco Sara, Bottani Emanuela, Dalla Pozza Elisa, Marroncelli Nunzio, Brandi Jessica, Cecconi Daniela, Decimo Ilaria, Migliorini Filippo, Zampieri Nicola, Dando Ilaria
Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Verona, Italy.
Department of Diagnostics and Public Health, University of Verona, Verona, Italy.
Cell Commun Signal. 2025 Jan 10;23(1):19. doi: 10.1186/s12964-024-01979-y.
Cryptorchidism is the absence of one or both testicles in the scrotum at birth, being a risk factor for testis cancer and infertility. The most effective method to treat cryptorchidism is orchiopexy, followed by human chorionic gonadotropin (hCG) therapy; however, a portion of treated patients do not show a significant improvement in testis volume and vascularization after adjuvant therapy.
In this study, we generated an in vitro model to predict the patient response to hCG by cultivating and treating primary cells derived from five cryptorchid patients' biopsies of gubernaculum testis, the ligament that connects the testicle to the scrotum. On these in vitro cultured cells, we analyzed the effect of hCG on cell proliferation, tubular structure formation, cellular respiration, reactive oxygen species content, and proteome.
We demonstrate that in vitro hCG stimulates gubernacular cells to proliferate and form vessel-like structures to a different extent among the five cryptorchid patients' cells, with a decrease in oxygen consumption and reactive oxygen species generation. Furthermore, from the proteomic analysis, we show that hCG regulates the intra- and extra-cellular organization of gubernacular cells together with a massive regulation of the antioxidant response.
Hereby, we characterized the cellular and molecular effects of hCG, demonstrating that the diverse patient response to hCG may be ascribable to their age since young patients better respond in vitro to the hormone, supporting a prompt surgical procedure and subsequent therapy.
The study was conducted in accordance with the Declaration of Helsinki and approved by the Institutional Ethics Committee of "Azienda Ospedaliera Universitaria Integrata" (AOUI) of Verona, Italy ("ANDRO-PRO", protocol code N. 4206 CESC of 26 April 2023).
隐睾症是指出生时一个或两个睾丸未降入阴囊，是睾丸癌和不育症的危险因素。治疗隐睾症最有效的方法是睾丸固定术，其次是人绒毛膜促性腺激素（hCG）疗法；然而，一部分接受治疗的患者在辅助治疗后睾丸体积和血管化并未显著改善。
在本研究中，我们通过培养和处理来自五名隐睾症患者睾丸引带活检的原代细胞，建立了一个体外模型来预测患者对hCG的反应，睾丸引带是连接睾丸与阴囊的韧带。在这些体外培养的细胞上，我们分析了hCG对细胞增殖、管状结构形成、细胞呼吸、活性氧含量和蛋白质组的影响。
我们证明，体外hCG刺激睾丸引带细胞增殖并在不同程度上形成血管样结构，这在五名隐睾症患者的细胞中存在差异，同时氧消耗和活性氧生成减少。此外，通过蛋白质组学分析，我们表明hCG调节睾丸引带细胞的细胞内和细胞外组织，同时对抗氧化反应进行大量调节。
在此，我们描述了hCG的细胞和分子效应，表明患者对hCG的不同反应可能归因于他们的年龄，因为年轻患者在体外对该激素的反应更好，这支持了尽早进行手术和后续治疗。
本研究遵循赫尔辛基宣言进行，并获得意大利维罗纳“综合大学医院”（AOUI）机构伦理委员会的批准（“ANDRO-PRO”，协议代码2023年4月26日第4206 CESC号）。
