Testis cell pyroptosis mediated by CASP1 and CASP4: possible sertoli cell-only syndrome pathogenesis
Abstract Background Sertoli cell-only syndrome (SCOS) is the most serious pathological type of non-obstructive azoospermia. Recently, several genes related to SCOS have been identified, including FANCM, TEX14, NR5A1, NANOS2, PLK4, WNK3, and FANCA, but they cannot fully explain the pathogenesis of SC...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-06-01
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| Series: | Reproductive Biology and Endocrinology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12958-023-01101-w |
| _version_ | 1797806433244282880 |
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| author | Wantao Liu Xinan Li Qiang Ma Yongtong Zhu Wenzhong Zhao Yisheng Yang Weiqiang Xiao Daxiong Huang Fengbo Cai David Yiu Leung Chan Shanchao Zhao Qingjun Chu |
| author_facet | Wantao Liu Xinan Li Qiang Ma Yongtong Zhu Wenzhong Zhao Yisheng Yang Weiqiang Xiao Daxiong Huang Fengbo Cai David Yiu Leung Chan Shanchao Zhao Qingjun Chu |
| author_sort | Wantao Liu |
| collection | DOAJ |
| description | Abstract Background Sertoli cell-only syndrome (SCOS) is the most serious pathological type of non-obstructive azoospermia. Recently, several genes related to SCOS have been identified, including FANCM, TEX14, NR5A1, NANOS2, PLK4, WNK3, and FANCA, but they cannot fully explain the pathogenesis of SCOS. This study attempted to explain spermatogenesis dysfunction in SCOS through testicular tissue RNA sequencing and to provide new targets for SCOS diagnosis and therapy. Methods We analyzed differentially expressed genes (DEGs) based on RNA sequencing of nine patients with SCOS and three patients with obstructive azoospermia and normal spermatogenesis. We further explored the identified genes using ELISA and immunohistochemistry. Results In total, 9406 DEGs were expressed (Log2|FC|≥ 1; adjusted P value < 0.05) in SCOS samples, and 21 hub genes were identified. Three upregulated core genes were found, including CASP4, CASP1, and PLA2G4A. Thus, we hypothesized that testis cell pyroptosis mediated by CASP1 and CASP4 might be involved in SCOS occurrence and development. ELISA verified that CASP1 and CASP4 activities in the testes of patients with SCOS were significantly higher than those in patients with normal spermatogenesis. Immunohistochemical results showed that CASP1 and CASP4 in the normal spermatogenesis group were mainly expressed in the nuclei of spermatogenic, Sertoli, and interstitial cells. CASP1 and CASP4 in the SCOS group were mainly expressed in the nuclei of Sertoli and interstitial cells because of the loss of spermatogonia and spermatocytes. CASP1 and CASP4 expression levels in the testes of patients with SCOS were significantly higher than those in patients with normal spermatogenisis. Furthermore, the pyroptosis-related proteins GSDMD and GSDME in the testes of patients with SCOS were also significantly higher than those in control patients. ELISA also showed that inflammatory factors (IL-1 β, IL-18, LDH, and ROS) were significantly increased in the SCOS group. Conclusions For the first time, we found that cell pyroptosis-related genes and key markers were significantly increased in the testes of patients with SCOS. We also observed many inflammatory and oxidative stress reactions in SCOS. Thus, we propose that testis cell pyroptosis mediated by CASP1 and CASP4 could participate in SCOS occurrence and development. |
| first_indexed | 2024-03-13T06:07:15Z |
| format | Article |
| id | doaj.art-582bf73145a644fb8efe3827a479018c |
| institution | Directory Open Access Journal |
| issn | 1477-7827 |
| language | English |
| last_indexed | 2024-03-13T06:07:15Z |
| publishDate | 2023-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Reproductive Biology and Endocrinology |
| spelling | doaj.art-582bf73145a644fb8efe3827a479018c2023-06-11T11:28:42ZengBMCReproductive Biology and Endocrinology1477-78272023-06-0121111410.1186/s12958-023-01101-wTestis cell pyroptosis mediated by CASP1 and CASP4: possible sertoli cell-only syndrome pathogenesisWantao Liu0Xinan Li1Qiang Ma2Yongtong Zhu3Wenzhong Zhao4Yisheng Yang5Weiqiang Xiao6Daxiong Huang7Fengbo Cai8David Yiu Leung Chan9Shanchao Zhao10Qingjun Chu11The First School of Clinical Medicine, Nanfang Hospital, Southern Medical UniversitySchool of Basic Medical Sciences, Guangzhou Medical UniversityThe First School of Clinical Medicine, Nanfang Hospital, Southern Medical UniversityThe First School of Clinical Medicine, Nanfang Hospital, Southern Medical UniversityNHC Key Laboratory of Male Reproduction and Genetics, Family Planning Research Institute of Guangdong ProvinceThe First School of Clinical Medicine, Nanfang Hospital, Southern Medical UniversityThe First School of Clinical Medicine, Nanfang Hospital, Southern Medical UniversityThe First School of Clinical Medicine, Nanfang Hospital, Southern Medical UniversityThe First School of Clinical Medicine, Nanfang Hospital, Southern Medical UniversityAssisted Reproductive Technology Unit, Department of Obstetrics and Gynaecology, Faculty of Medicine, The Chinese University of Hong Kong, Prince of Wales HospitalThe First School of Clinical Medicine, Nanfang Hospital, Southern Medical UniversityThe First School of Clinical Medicine, Nanfang Hospital, Southern Medical UniversityAbstract Background Sertoli cell-only syndrome (SCOS) is the most serious pathological type of non-obstructive azoospermia. Recently, several genes related to SCOS have been identified, including FANCM, TEX14, NR5A1, NANOS2, PLK4, WNK3, and FANCA, but they cannot fully explain the pathogenesis of SCOS. This study attempted to explain spermatogenesis dysfunction in SCOS through testicular tissue RNA sequencing and to provide new targets for SCOS diagnosis and therapy. Methods We analyzed differentially expressed genes (DEGs) based on RNA sequencing of nine patients with SCOS and three patients with obstructive azoospermia and normal spermatogenesis. We further explored the identified genes using ELISA and immunohistochemistry. Results In total, 9406 DEGs were expressed (Log2|FC|≥ 1; adjusted P value < 0.05) in SCOS samples, and 21 hub genes were identified. Three upregulated core genes were found, including CASP4, CASP1, and PLA2G4A. Thus, we hypothesized that testis cell pyroptosis mediated by CASP1 and CASP4 might be involved in SCOS occurrence and development. ELISA verified that CASP1 and CASP4 activities in the testes of patients with SCOS were significantly higher than those in patients with normal spermatogenesis. Immunohistochemical results showed that CASP1 and CASP4 in the normal spermatogenesis group were mainly expressed in the nuclei of spermatogenic, Sertoli, and interstitial cells. CASP1 and CASP4 in the SCOS group were mainly expressed in the nuclei of Sertoli and interstitial cells because of the loss of spermatogonia and spermatocytes. CASP1 and CASP4 expression levels in the testes of patients with SCOS were significantly higher than those in patients with normal spermatogenisis. Furthermore, the pyroptosis-related proteins GSDMD and GSDME in the testes of patients with SCOS were also significantly higher than those in control patients. ELISA also showed that inflammatory factors (IL-1 β, IL-18, LDH, and ROS) were significantly increased in the SCOS group. Conclusions For the first time, we found that cell pyroptosis-related genes and key markers were significantly increased in the testes of patients with SCOS. We also observed many inflammatory and oxidative stress reactions in SCOS. Thus, we propose that testis cell pyroptosis mediated by CASP1 and CASP4 could participate in SCOS occurrence and development.https://doi.org/10.1186/s12958-023-01101-wSertoli cell-only syndrome (SCOS)CASP1CASP4Pyroptosis |
| spellingShingle | Wantao Liu Xinan Li Qiang Ma Yongtong Zhu Wenzhong Zhao Yisheng Yang Weiqiang Xiao Daxiong Huang Fengbo Cai David Yiu Leung Chan Shanchao Zhao Qingjun Chu Testis cell pyroptosis mediated by CASP1 and CASP4: possible sertoli cell-only syndrome pathogenesis Reproductive Biology and Endocrinology Sertoli cell-only syndrome (SCOS) CASP1 CASP4 Pyroptosis |
| title | Testis cell pyroptosis mediated by CASP1 and CASP4: possible sertoli cell-only syndrome pathogenesis |
| title_full | Testis cell pyroptosis mediated by CASP1 and CASP4: possible sertoli cell-only syndrome pathogenesis |
| title_fullStr | Testis cell pyroptosis mediated by CASP1 and CASP4: possible sertoli cell-only syndrome pathogenesis |
| title_full_unstemmed | Testis cell pyroptosis mediated by CASP1 and CASP4: possible sertoli cell-only syndrome pathogenesis |
| title_short | Testis cell pyroptosis mediated by CASP1 and CASP4: possible sertoli cell-only syndrome pathogenesis |
| title_sort | testis cell pyroptosis mediated by casp1 and casp4 possible sertoli cell only syndrome pathogenesis |
| topic | Sertoli cell-only syndrome (SCOS) CASP1 CASP4 Pyroptosis |
| url | https://doi.org/10.1186/s12958-023-01101-w |
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