In vitro effect of hCG on cryptorchid patients’ gubernacular cells: a predictive model for adjuvant personalized therapy

Abstract Background 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 tr...

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Main Authors: Andrea Errico, Giulia Ambrosini, Sara Vinco, Emanuela Bottani, Elisa Dalla Pozza, Nunzio Marroncelli, Jessica Brandi, Daniela Cecconi, Ilaria Decimo, Filippo Migliorini, Nicola Zampieri, Ilaria Dando
Format: Article
Language:English
Published: BMC 2025-01-01
Series:Cell Communication and Signaling
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Online Access:https://doi.org/10.1186/s12964-024-01979-y
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author Andrea Errico
Giulia Ambrosini
Sara Vinco
Emanuela Bottani
Elisa Dalla Pozza
Nunzio Marroncelli
Jessica Brandi
Daniela Cecconi
Ilaria Decimo
Filippo Migliorini
Nicola Zampieri
Ilaria Dando
author_facet Andrea Errico
Giulia Ambrosini
Sara Vinco
Emanuela Bottani
Elisa Dalla Pozza
Nunzio Marroncelli
Jessica Brandi
Daniela Cecconi
Ilaria Decimo
Filippo Migliorini
Nicola Zampieri
Ilaria Dando
author_sort Andrea Errico
collection DOAJ
description Abstract Background 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. Methods 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. Results 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. Conclusions 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. Trial registration 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).
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spelling doaj-art-b2696cd92d0b4c2a9bf0da6175ebefa52025-01-12T12:33:02ZengBMCCell Communication and Signaling1478-811X2025-01-0123111910.1186/s12964-024-01979-yIn vitro effect of hCG on cryptorchid patients’ gubernacular cells: a predictive model for adjuvant personalized therapyAndrea Errico0Giulia Ambrosini1Sara Vinco2Emanuela Bottani3Elisa Dalla Pozza4Nunzio Marroncelli5Jessica Brandi6Daniela Cecconi7Ilaria Decimo8Filippo Migliorini9Nicola Zampieri10Ilaria Dando11Department of Neurosciences, Biomedicine and Movement Sciences, University of VeronaDepartment of Neurosciences, Biomedicine and Movement Sciences, University of VeronaDepartment of Neurosciences, Biomedicine and Movement Sciences, University of VeronaDepartment of Diagnostics and Public Health, University of VeronaDepartment of Neurosciences, Biomedicine and Movement Sciences, University of VeronaDepartment of Neurosciences, Biomedicine and Movement Sciences, University of VeronaDepartment of Biotechnology, University of VeronaDepartment of Biotechnology, University of VeronaDepartment of Diagnostics and Public Health, University of VeronaUOC of Urology, Azienda Ospedaliera Universitaria Integrata di VeronaDepartment of Engineering and Innovation Medicine, Paediatric Fertility Lab, Woman and Child Hospital, Division of Pediatric Surgery, University of VeronaDepartment of Neurosciences, Biomedicine and Movement Sciences, University of VeronaAbstract Background 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. Methods 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. Results 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. Conclusions 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. Trial registration 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).https://doi.org/10.1186/s12964-024-01979-yCryptorchidismGubernaculum testisEnergetic metabolismHuman chorionic gonadotropinOxidative stress
spellingShingle Andrea Errico
Giulia Ambrosini
Sara Vinco
Emanuela Bottani
Elisa Dalla Pozza
Nunzio Marroncelli
Jessica Brandi
Daniela Cecconi
Ilaria Decimo
Filippo Migliorini
Nicola Zampieri
Ilaria Dando
In vitro effect of hCG on cryptorchid patients’ gubernacular cells: a predictive model for adjuvant personalized therapy
Cell Communication and Signaling
Cryptorchidism
Gubernaculum testis
Energetic metabolism
Human chorionic gonadotropin
Oxidative stress
title In vitro effect of hCG on cryptorchid patients’ gubernacular cells: a predictive model for adjuvant personalized therapy
title_full In vitro effect of hCG on cryptorchid patients’ gubernacular cells: a predictive model for adjuvant personalized therapy
title_fullStr In vitro effect of hCG on cryptorchid patients’ gubernacular cells: a predictive model for adjuvant personalized therapy
title_full_unstemmed In vitro effect of hCG on cryptorchid patients’ gubernacular cells: a predictive model for adjuvant personalized therapy
title_short In vitro effect of hCG on cryptorchid patients’ gubernacular cells: a predictive model for adjuvant personalized therapy
title_sort in vitro effect of hcg on cryptorchid patients gubernacular cells a predictive model for adjuvant personalized therapy
topic Cryptorchidism
Gubernaculum testis
Energetic metabolism
Human chorionic gonadotropin
Oxidative stress
url https://doi.org/10.1186/s12964-024-01979-y
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