Cell-Cell Interaction-Mediated Signaling in the Testis Induces Reproductive Dysfunction—Lesson from the Toxicant/Pharmaceutical Models
Emerging evidence has shown that cell-cell interactions between testicular cells, in particular at the Sertoli cell-cell and Sertoli-germ cell interface, are crucial to support spermatogenesis. The unique ultrastructures that support cell-cell interactions in the testis are the basal ES (ectoplasmic...
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MDPI AG
2022-02-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/11/4/591 |
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| author | Lingling Wang Tiao Bu Xiaolong Wu Sheng Gao Xinyao Li Angela Bryanne De Jesus Chris K. C. Wong Hao Chen Nancy P. Y. Chung Fei Sun C. Yan Cheng |
| author_facet | Lingling Wang Tiao Bu Xiaolong Wu Sheng Gao Xinyao Li Angela Bryanne De Jesus Chris K. C. Wong Hao Chen Nancy P. Y. Chung Fei Sun C. Yan Cheng |
| author_sort | Lingling Wang |
| collection | DOAJ |
| description | Emerging evidence has shown that cell-cell interactions between testicular cells, in particular at the Sertoli cell-cell and Sertoli-germ cell interface, are crucial to support spermatogenesis. The unique ultrastructures that support cell-cell interactions in the testis are the basal ES (ectoplasmic specialization) and the apical ES. The basal ES is found between adjacent Sertoli cells near the basement membrane that also constitute the blood-testis barrier (BTB). The apical ES is restrictively expressed at the Sertoli-spermatid contact site in the apical (adluminal) compartment of the seminiferous epithelium. These ultrastructures are present in both rodent and human testes, but the majority of studies found in the literature were done in rodent testes. As such, our discussion herein, unless otherwise specified, is focused on studies in testes of adult rats. Studies have shown that the testicular cell-cell interactions crucial to support spermatogenesis are mediated through distinctive signaling proteins and pathways, most notably involving FAK, Akt1/2 and Cdc42 GTPase. Thus, manipulation of some of these signaling proteins, such as FAK, through the use of phosphomimetic mutants for overexpression in Sertoli cell epithelium in vitro or in the testis in vivo, making FAK either constitutively active or inactive, we can modify the outcome of spermatogenesis. For instance, using the toxicant-induced Sertoli cell or testis injury in rats as study models, we can either block or rescue toxicant-induced infertility through overexpression of p-FAK-Y397 or p-FAK-Y407 (and their mutants), including the use of specific activator(s) of the involved signaling proteins against pAkt1/2. These findings thus illustrate that a potential therapeutic approach can be developed to manage toxicant-induced male reproductive dysfunction. In this review, we critically evaluate these recent findings, highlighting the direction for future investigations by bringing the laboratory-based research through a translation path to clinical investigations. |
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| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-09T22:21:18Z |
| publishDate | 2022-02-01 |
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| spelling | doaj.art-84b4a70afad84f6aba584b60ddeaba6d2023-11-23T19:13:44ZengMDPI AGCells2073-44092022-02-0111459110.3390/cells11040591Cell-Cell Interaction-Mediated Signaling in the Testis Induces Reproductive Dysfunction—Lesson from the Toxicant/Pharmaceutical ModelsLingling Wang0Tiao Bu1Xiaolong Wu2Sheng Gao3Xinyao Li4Angela Bryanne De Jesus5Chris K. C. Wong6Hao Chen7Nancy P. Y. Chung8Fei Sun9C. Yan Cheng10Department of Urology and Andrology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310016, ChinaDepartment of Urology and Andrology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310016, ChinaDepartment of Urology and Andrology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310016, ChinaDepartment of Urology and Andrology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310016, ChinaInstitute of Reproductive Medicine, Nantong University School of Medicine, Nantong 226001, ChinaDepartment of Biology, Nyack College, New York, NY 10004, USADepartment of Biology, Croucher Institute for Environmental Sciences, Hong Kong Baptist University, Hong Kong, ChinaInstitute of Reproductive Medicine, Nantong University School of Medicine, Nantong 226001, ChinaDepartment of Genetic Medicine, Cornell Medical College, New York, NY 10065, USADepartment of Urology and Andrology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310016, ChinaDepartment of Urology and Andrology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310016, ChinaEmerging evidence has shown that cell-cell interactions between testicular cells, in particular at the Sertoli cell-cell and Sertoli-germ cell interface, are crucial to support spermatogenesis. The unique ultrastructures that support cell-cell interactions in the testis are the basal ES (ectoplasmic specialization) and the apical ES. The basal ES is found between adjacent Sertoli cells near the basement membrane that also constitute the blood-testis barrier (BTB). The apical ES is restrictively expressed at the Sertoli-spermatid contact site in the apical (adluminal) compartment of the seminiferous epithelium. These ultrastructures are present in both rodent and human testes, but the majority of studies found in the literature were done in rodent testes. As such, our discussion herein, unless otherwise specified, is focused on studies in testes of adult rats. Studies have shown that the testicular cell-cell interactions crucial to support spermatogenesis are mediated through distinctive signaling proteins and pathways, most notably involving FAK, Akt1/2 and Cdc42 GTPase. Thus, manipulation of some of these signaling proteins, such as FAK, through the use of phosphomimetic mutants for overexpression in Sertoli cell epithelium in vitro or in the testis in vivo, making FAK either constitutively active or inactive, we can modify the outcome of spermatogenesis. For instance, using the toxicant-induced Sertoli cell or testis injury in rats as study models, we can either block or rescue toxicant-induced infertility through overexpression of p-FAK-Y397 or p-FAK-Y407 (and their mutants), including the use of specific activator(s) of the involved signaling proteins against pAkt1/2. These findings thus illustrate that a potential therapeutic approach can be developed to manage toxicant-induced male reproductive dysfunction. In this review, we critically evaluate these recent findings, highlighting the direction for future investigations by bringing the laboratory-based research through a translation path to clinical investigations.https://www.mdpi.com/2073-4409/11/4/591testistoxicantscadmiumPFOSadjudincell-cell interactions |
| spellingShingle | Lingling Wang Tiao Bu Xiaolong Wu Sheng Gao Xinyao Li Angela Bryanne De Jesus Chris K. C. Wong Hao Chen Nancy P. Y. Chung Fei Sun C. Yan Cheng Cell-Cell Interaction-Mediated Signaling in the Testis Induces Reproductive Dysfunction—Lesson from the Toxicant/Pharmaceutical Models Cells testis toxicants cadmium PFOS adjudin cell-cell interactions |
| title | Cell-Cell Interaction-Mediated Signaling in the Testis Induces Reproductive Dysfunction—Lesson from the Toxicant/Pharmaceutical Models |
| title_full | Cell-Cell Interaction-Mediated Signaling in the Testis Induces Reproductive Dysfunction—Lesson from the Toxicant/Pharmaceutical Models |
| title_fullStr | Cell-Cell Interaction-Mediated Signaling in the Testis Induces Reproductive Dysfunction—Lesson from the Toxicant/Pharmaceutical Models |
| title_full_unstemmed | Cell-Cell Interaction-Mediated Signaling in the Testis Induces Reproductive Dysfunction—Lesson from the Toxicant/Pharmaceutical Models |
| title_short | Cell-Cell Interaction-Mediated Signaling in the Testis Induces Reproductive Dysfunction—Lesson from the Toxicant/Pharmaceutical Models |
| title_sort | cell cell interaction mediated signaling in the testis induces reproductive dysfunction lesson from the toxicant pharmaceutical models |
| topic | testis toxicants cadmium PFOS adjudin cell-cell interactions |
| url | https://www.mdpi.com/2073-4409/11/4/591 |
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