ARHGEF15 in Sertoli cells contributes to germ cell development and testicular immune privilege
Sertoli cells (SCs), the only somatic cells in the seminiferous tubules, facilitate the maintenance of testicular immune privilege through the formation of the blood-testis barrier (BTB) and the expression of immunoregulatory factors. Rho guanosine exchange factor 15 (ARHGEF15) is a member of the gu...
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| Veröffentlicht in: | Biology of reproduction 2022-12, Vol.107 (6), p.1565-1579 |
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| creator | Chen, Feng Wu, Yingjie Ke, Lu Lin, Xinyi Wang, Fengchao Qin, Yinghe |
| description | Sertoli cells (SCs), the only somatic cells in the seminiferous tubules, facilitate the maintenance of testicular immune privilege through the formation of the blood-testis barrier (BTB) and the expression of immunoregulatory factors. Rho guanosine exchange factor 15 (ARHGEF15) is a member of the guanosine exchange factors, which are involved in cell migration, cell polarity, and cell cycle progression via activation of Rho GTPases. This study investigated the functional role of ARHGEF15 in SCs during spermatogenesis using SC–specific Arhgef15 knockout mice. The results revealed that Arhgef15 deficiency in SCs affected the localization of SC nuclei, disrupted BTB integrity, and led to premature shedding of germ cells. In Arhgef15flox/flox/Amh-Cre+ mice, the ultrastructure of the round spermatids was impaired, accompanied by acrosome degeneration, acrosomal vesicle shedding, and atrophic nuclei. Consequently, the percentage of abnormal sperm in the Arhgef15flox/flox/AmhCre+ epididymis was markedly elevated. RNA-sequencing analysis revealed that most of the differentially expressed genes in SCs of Arhgef15flox/flox/Amh-Cre+ mice were associated with immunity. Further study revealed that the sera of Arhgef15flox/flox/Amh-Cre+ mice showed immunoreactivity against testicular lysate of wild-type mice, indicating the production of antibodies against testicular autoantigens in Arhgef15flox/flox/Amh-Cre+ mice. In conclusion, the specific deletion of Arhgef15 in SCs of mice leads to sperm abnormality, probably by disrupting the testicular immune homeostasis. Summary Sentence Guanylate exchange factor Arhgef15 is required for the development of germ cells by maintaining the balance of immune-related factors in mouse testes. |
| doi_str_mv | 10.1093/biolre/ioac166 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2706181847</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><oup_id>10.1093/biolre/ioac166</oup_id><sourcerecordid>2823840944</sourcerecordid><originalsourceid>FETCH-LOGICAL-b394t-6e0431c9f2ea1f4f2bb7c9b766b0dfece7e20d773c9ef6c5b0bfad71107525bd3</originalsourceid><addsrcrecordid>eNqF0M1LwzAYBvAgis7p1aMEvChYl482aY9juCkMBD-uhiZ9K5G2mUkr-N8b7fTgxVNC8svLkwehE0quKCn4TFvXeJhZVxoqxA6a0IwViWQi30UTQohIOBf8AB2G8EoITTnj--iAi7jnWT5Bz_P7m9X1kmbYdvgBfO8aiw00TcDGdb23eugh4N7hF_Dt9w2u4B0at2mh63HZVTiC3pqhKT22bTt0gDfevtsGXuAI7dVlE-B4u07R0_L6cXGTrO9Wt4v5OtG8SPtEAEk5NUXNoKR1WjOtpSm0FEKTqgYDEhippOSmgFqYTBNdl5WklMiMZbriU3Q-zt149zbEPKq14Sts2YEbgmKSCJrTPJWRnv2hr27wXUynWM54npIiTaO6GpXxLgQPtYp_akv_oShRX82rsXm1bT4-ON2OHXQL1S__qTqCixG4YfP_sMvRxnPXwX_8E9rbnzc</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2823840944</pqid></control><display><type>article</type><title>ARHGEF15 in Sertoli cells contributes to germ cell development and testicular immune privilege</title><source>Oxford University Press Journals All Titles (1996-Current)</source><source>MEDLINE</source><source>EZB-FREE-00999 freely available EZB journals</source><source>Alma/SFX Local Collection</source><creator>Chen, Feng ; Wu, Yingjie ; Ke, Lu ; Lin, Xinyi ; Wang, Fengchao ; Qin, Yinghe</creator><creatorcontrib>Chen, Feng ; Wu, Yingjie ; Ke, Lu ; Lin, Xinyi ; Wang, Fengchao ; Qin, Yinghe</creatorcontrib><description>Sertoli cells (SCs), the only somatic cells in the seminiferous tubules, facilitate the maintenance of testicular immune privilege through the formation of the blood-testis barrier (BTB) and the expression of immunoregulatory factors. Rho guanosine exchange factor 15 (ARHGEF15) is a member of the guanosine exchange factors, which are involved in cell migration, cell polarity, and cell cycle progression via activation of Rho GTPases. This study investigated the functional role of ARHGEF15 in SCs during spermatogenesis using SC–specific Arhgef15 knockout mice. The results revealed that Arhgef15 deficiency in SCs affected the localization of SC nuclei, disrupted BTB integrity, and led to premature shedding of germ cells. In Arhgef15flox/flox/Amh-Cre+ mice, the ultrastructure of the round spermatids was impaired, accompanied by acrosome degeneration, acrosomal vesicle shedding, and atrophic nuclei. Consequently, the percentage of abnormal sperm in the Arhgef15flox/flox/AmhCre+ epididymis was markedly elevated. RNA-sequencing analysis revealed that most of the differentially expressed genes in SCs of Arhgef15flox/flox/Amh-Cre+ mice were associated with immunity. Further study revealed that the sera of Arhgef15flox/flox/Amh-Cre+ mice showed immunoreactivity against testicular lysate of wild-type mice, indicating the production of antibodies against testicular autoantigens in Arhgef15flox/flox/Amh-Cre+ mice. In conclusion, the specific deletion of Arhgef15 in SCs of mice leads to sperm abnormality, probably by disrupting the testicular immune homeostasis. Summary Sentence Guanylate exchange factor Arhgef15 is required for the development of germ cells by maintaining the balance of immune-related factors in mouse testes.</description><identifier>ISSN: 0006-3363</identifier><identifier>EISSN: 1529-7268</identifier><identifier>DOI: 10.1093/biolre/ioac166</identifier><identifier>PMID: 36001358</identifier><language>eng</language><publisher>United States: Society for the Study of Reproduction</publisher><subject>Animals ; Arhgef15 ; Autoantigens ; Cell activation ; Cell cycle ; Cell migration ; Epididymis ; Germ cells ; Guanosine - metabolism ; Homeostasis ; Immune Privilege ; Immunoreactivity ; Immunoregulation ; Immunoregulatory factors ; knockout ; Localization ; Male ; Mice ; Mice, Knockout ; RESEARCH ARTICLE ; Semen ; Sequence analysis ; Sertoli cells ; Sertoli Cells - metabolism ; Somatic cells ; Sperm ; Spermatids ; Spermatogenesis ; Spermatogenesis - physiology ; Spermatozoa - metabolism ; Testes ; testicular immune privilege ; Testis - metabolism ; Tubules ; Ultrastructure</subject><ispartof>Biology of reproduction, 2022-12, Vol.107 (6), p.1565-1579</ispartof><rights>The Author(s) 2022. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com journals.permissions@oup.com</rights><rights>The Author(s) 2022. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com 2022</rights><rights>The Author(s) 2022. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.</rights><rights>The Author(s) 2022. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-b394t-6e0431c9f2ea1f4f2bb7c9b766b0dfece7e20d773c9ef6c5b0bfad71107525bd3</citedby><cites>FETCH-LOGICAL-b394t-6e0431c9f2ea1f4f2bb7c9b766b0dfece7e20d773c9ef6c5b0bfad71107525bd3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,1578,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/36001358$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Chen, Feng</creatorcontrib><creatorcontrib>Wu, Yingjie</creatorcontrib><creatorcontrib>Ke, Lu</creatorcontrib><creatorcontrib>Lin, Xinyi</creatorcontrib><creatorcontrib>Wang, Fengchao</creatorcontrib><creatorcontrib>Qin, Yinghe</creatorcontrib><title>ARHGEF15 in Sertoli cells contributes to germ cell development and testicular immune privilege</title><title>Biology of reproduction</title><addtitle>Biol Reprod</addtitle><description>Sertoli cells (SCs), the only somatic cells in the seminiferous tubules, facilitate the maintenance of testicular immune privilege through the formation of the blood-testis barrier (BTB) and the expression of immunoregulatory factors. Rho guanosine exchange factor 15 (ARHGEF15) is a member of the guanosine exchange factors, which are involved in cell migration, cell polarity, and cell cycle progression via activation of Rho GTPases. This study investigated the functional role of ARHGEF15 in SCs during spermatogenesis using SC–specific Arhgef15 knockout mice. The results revealed that Arhgef15 deficiency in SCs affected the localization of SC nuclei, disrupted BTB integrity, and led to premature shedding of germ cells. In Arhgef15flox/flox/Amh-Cre+ mice, the ultrastructure of the round spermatids was impaired, accompanied by acrosome degeneration, acrosomal vesicle shedding, and atrophic nuclei. Consequently, the percentage of abnormal sperm in the Arhgef15flox/flox/AmhCre+ epididymis was markedly elevated. RNA-sequencing analysis revealed that most of the differentially expressed genes in SCs of Arhgef15flox/flox/Amh-Cre+ mice were associated with immunity. Further study revealed that the sera of Arhgef15flox/flox/Amh-Cre+ mice showed immunoreactivity against testicular lysate of wild-type mice, indicating the production of antibodies against testicular autoantigens in Arhgef15flox/flox/Amh-Cre+ mice. In conclusion, the specific deletion of Arhgef15 in SCs of mice leads to sperm abnormality, probably by disrupting the testicular immune homeostasis. Summary Sentence Guanylate exchange factor Arhgef15 is required for the development of germ cells by maintaining the balance of immune-related factors in mouse testes.</description><subject>Animals</subject><subject>Arhgef15</subject><subject>Autoantigens</subject><subject>Cell activation</subject><subject>Cell cycle</subject><subject>Cell migration</subject><subject>Epididymis</subject><subject>Germ cells</subject><subject>Guanosine - metabolism</subject><subject>Homeostasis</subject><subject>Immune Privilege</subject><subject>Immunoreactivity</subject><subject>Immunoregulation</subject><subject>Immunoregulatory factors</subject><subject>knockout</subject><subject>Localization</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, Knockout</subject><subject>RESEARCH ARTICLE</subject><subject>Semen</subject><subject>Sequence analysis</subject><subject>Sertoli cells</subject><subject>Sertoli Cells - metabolism</subject><subject>Somatic cells</subject><subject>Sperm</subject><subject>Spermatids</subject><subject>Spermatogenesis</subject><subject>Spermatogenesis - physiology</subject><subject>Spermatozoa - metabolism</subject><subject>Testes</subject><subject>testicular immune privilege</subject><subject>Testis - metabolism</subject><subject>Tubules</subject><subject>Ultrastructure</subject><issn>0006-3363</issn><issn>1529-7268</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNqF0M1LwzAYBvAgis7p1aMEvChYl482aY9juCkMBD-uhiZ9K5G2mUkr-N8b7fTgxVNC8svLkwehE0quKCn4TFvXeJhZVxoqxA6a0IwViWQi30UTQohIOBf8AB2G8EoITTnj--iAi7jnWT5Bz_P7m9X1kmbYdvgBfO8aiw00TcDGdb23eugh4N7hF_Dt9w2u4B0at2mh63HZVTiC3pqhKT22bTt0gDfevtsGXuAI7dVlE-B4u07R0_L6cXGTrO9Wt4v5OtG8SPtEAEk5NUXNoKR1WjOtpSm0FEKTqgYDEhippOSmgFqYTBNdl5WklMiMZbriU3Q-zt149zbEPKq14Sts2YEbgmKSCJrTPJWRnv2hr27wXUynWM54npIiTaO6GpXxLgQPtYp_akv_oShRX82rsXm1bT4-ON2OHXQL1S__qTqCixG4YfP_sMvRxnPXwX_8E9rbnzc</recordid><startdate>20221210</startdate><enddate>20221210</enddate><creator>Chen, Feng</creator><creator>Wu, Yingjie</creator><creator>Ke, Lu</creator><creator>Lin, Xinyi</creator><creator>Wang, Fengchao</creator><creator>Qin, Yinghe</creator><general>Society for the Study of Reproduction</general><general>Oxford University Press</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>20221210</creationdate><title>ARHGEF15 in Sertoli cells contributes to germ cell development and testicular immune privilege</title><author>Chen, Feng ; Wu, Yingjie ; Ke, Lu ; Lin, Xinyi ; Wang, Fengchao ; Qin, Yinghe</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-b394t-6e0431c9f2ea1f4f2bb7c9b766b0dfece7e20d773c9ef6c5b0bfad71107525bd3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Animals</topic><topic>Arhgef15</topic><topic>Autoantigens</topic><topic>Cell activation</topic><topic>Cell cycle</topic><topic>Cell migration</topic><topic>Epididymis</topic><topic>Germ cells</topic><topic>Guanosine - metabolism</topic><topic>Homeostasis</topic><topic>Immune Privilege</topic><topic>Immunoreactivity</topic><topic>Immunoregulation</topic><topic>Immunoregulatory factors</topic><topic>knockout</topic><topic>Localization</topic><topic>Male</topic><topic>Mice</topic><topic>Mice, Knockout</topic><topic>RESEARCH ARTICLE</topic><topic>Semen</topic><topic>Sequence analysis</topic><topic>Sertoli cells</topic><topic>Sertoli Cells - metabolism</topic><topic>Somatic cells</topic><topic>Sperm</topic><topic>Spermatids</topic><topic>Spermatogenesis</topic><topic>Spermatogenesis - physiology</topic><topic>Spermatozoa - metabolism</topic><topic>Testes</topic><topic>testicular immune privilege</topic><topic>Testis - metabolism</topic><topic>Tubules</topic><topic>Ultrastructure</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Chen, Feng</creatorcontrib><creatorcontrib>Wu, Yingjie</creatorcontrib><creatorcontrib>Ke, Lu</creatorcontrib><creatorcontrib>Lin, Xinyi</creatorcontrib><creatorcontrib>Wang, Fengchao</creatorcontrib><creatorcontrib>Qin, Yinghe</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Biology of reproduction</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Chen, Feng</au><au>Wu, Yingjie</au><au>Ke, Lu</au><au>Lin, Xinyi</au><au>Wang, Fengchao</au><au>Qin, Yinghe</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>ARHGEF15 in Sertoli cells contributes to germ cell development and testicular immune privilege</atitle><jtitle>Biology of reproduction</jtitle><addtitle>Biol Reprod</addtitle><date>2022-12-10</date><risdate>2022</risdate><volume>107</volume><issue>6</issue><spage>1565</spage><epage>1579</epage><pages>1565-1579</pages><issn>0006-3363</issn><eissn>1529-7268</eissn><abstract>Sertoli cells (SCs), the only somatic cells in the seminiferous tubules, facilitate the maintenance of testicular immune privilege through the formation of the blood-testis barrier (BTB) and the expression of immunoregulatory factors. Rho guanosine exchange factor 15 (ARHGEF15) is a member of the guanosine exchange factors, which are involved in cell migration, cell polarity, and cell cycle progression via activation of Rho GTPases. This study investigated the functional role of ARHGEF15 in SCs during spermatogenesis using SC–specific Arhgef15 knockout mice. The results revealed that Arhgef15 deficiency in SCs affected the localization of SC nuclei, disrupted BTB integrity, and led to premature shedding of germ cells. In Arhgef15flox/flox/Amh-Cre+ mice, the ultrastructure of the round spermatids was impaired, accompanied by acrosome degeneration, acrosomal vesicle shedding, and atrophic nuclei. Consequently, the percentage of abnormal sperm in the Arhgef15flox/flox/AmhCre+ epididymis was markedly elevated. RNA-sequencing analysis revealed that most of the differentially expressed genes in SCs of Arhgef15flox/flox/Amh-Cre+ mice were associated with immunity. Further study revealed that the sera of Arhgef15flox/flox/Amh-Cre+ mice showed immunoreactivity against testicular lysate of wild-type mice, indicating the production of antibodies against testicular autoantigens in Arhgef15flox/flox/Amh-Cre+ mice. In conclusion, the specific deletion of Arhgef15 in SCs of mice leads to sperm abnormality, probably by disrupting the testicular immune homeostasis. Summary Sentence Guanylate exchange factor Arhgef15 is required for the development of germ cells by maintaining the balance of immune-related factors in mouse testes.</abstract><cop>United States</cop><pub>Society for the Study of Reproduction</pub><pmid>36001358</pmid><doi>10.1093/biolre/ioac166</doi><tpages>15</tpages></addata></record> |
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| source | Oxford University Press Journals All Titles (1996-Current); MEDLINE; EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
| subjects | Animals Arhgef15 Autoantigens Cell activation Cell cycle Cell migration Epididymis Germ cells Guanosine - metabolism Homeostasis Immune Privilege Immunoreactivity Immunoregulation Immunoregulatory factors knockout Localization Male Mice Mice, Knockout RESEARCH ARTICLE Semen Sequence analysis Sertoli cells Sertoli Cells - metabolism Somatic cells Sperm Spermatids Spermatogenesis Spermatogenesis - physiology Spermatozoa - metabolism Testes testicular immune privilege Testis - metabolism Tubules Ultrastructure |
| title | ARHGEF15 in Sertoli cells contributes to germ cell development and testicular immune privilege |
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