Hormone suppression with GnRH antagonist promotes spermatogenic recovery from transplanted spermatogonial stem cells in irradiated cynomolgus monkeys
Summary Hormone suppression given before or after cytotoxic treatment stimulates the recovery of spermatogenesis from endogenous and transplanted spermatogonial stem cells (SSC) and restores fertility in rodents. To test whether the combination of hormone suppression and transplantation could enhanc...
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| Veröffentlicht in: | Andrology (Oxford) 2013-11, Vol.1 (6), p.886-898 |
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| creator | Shetty, G. Uthamanthil, R. K. Zhou, W. Shao, S. H. Weng, C. C. Tailor, R. C. Hermann, B. P. Orwig, K. E. Meistrich, M. L. |
| description | Summary
Hormone suppression given before or after cytotoxic treatment stimulates the recovery of spermatogenesis from endogenous and transplanted spermatogonial stem cells (SSC) and restores fertility in rodents. To test whether the combination of hormone suppression and transplantation could enhance the recovery of spermatogenesis in primates, we irradiated (7 Gy) the testes of 12 adult cynomolgus monkeys and treated six of them with gonadotropin‐releasing hormone antagonist (GnRH‐ant) for 8 weeks. At the end of this treatment, we transfected cryopreserved testicular cells with green fluorescent protein‐lentivirus and autologously transplanted them back into one of the testes. The only significant effect of GnRH‐ant treatment on endogenous spermatogenesis was an increase in the percentage of tubules containing differentiated germ cells (tubule differentiation index; TDI) in the sham‐transplanted testes of GnRH‐ant–treated monkeys compared with radiation‐only monkeys at 24 weeks after irradiation. Although transplantation alone after irradiation did not significantly increase the TDI, detection of lentiviral DNA in the spermatozoa of one radiation‐only monkey indicated that some transplanted cells colonized the testis. However, the combination of transplantation and GnRH‐ant clearly stimulated spermatogenic recovery as evidenced by several observations in the GnRH‐ant–treated monkeys receiving transplantation: (i) significant increases (~20%) in the volume and weight of the testes compared with the contralateral sham‐transplanted testes and/or to the transplanted testes of the radiation‐only monkeys; (ii) increases in TDI compared to the transplanted testes of radiation‐only monkeys at 24 weeks (9.6% vs. 2.9%; p = 0.05) and 44 weeks (16.5% vs. 6.1%, p = 0.055); (iii) detection of lentiviral sequences in the spermatozoa or testes of five of the GnRH‐ant–treated monkeys and (iv) significantly higher sperm counts than in the radiation‐only monkeys. Thus hormone suppression enhances spermatogenic recovery from transplanted SSC in primates and may be a useful tool in conjunction with spermatogonial transplantation to restore fertility in men after cancer treatment. |
| doi_str_mv | 10.1111/j.2047-2927.2013.00126.x |
| format | Article |
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Hormone suppression given before or after cytotoxic treatment stimulates the recovery of spermatogenesis from endogenous and transplanted spermatogonial stem cells (SSC) and restores fertility in rodents. To test whether the combination of hormone suppression and transplantation could enhance the recovery of spermatogenesis in primates, we irradiated (7 Gy) the testes of 12 adult cynomolgus monkeys and treated six of them with gonadotropin‐releasing hormone antagonist (GnRH‐ant) for 8 weeks. At the end of this treatment, we transfected cryopreserved testicular cells with green fluorescent protein‐lentivirus and autologously transplanted them back into one of the testes. The only significant effect of GnRH‐ant treatment on endogenous spermatogenesis was an increase in the percentage of tubules containing differentiated germ cells (tubule differentiation index; TDI) in the sham‐transplanted testes of GnRH‐ant–treated monkeys compared with radiation‐only monkeys at 24 weeks after irradiation. Although transplantation alone after irradiation did not significantly increase the TDI, detection of lentiviral DNA in the spermatozoa of one radiation‐only monkey indicated that some transplanted cells colonized the testis. However, the combination of transplantation and GnRH‐ant clearly stimulated spermatogenic recovery as evidenced by several observations in the GnRH‐ant–treated monkeys receiving transplantation: (i) significant increases (~20%) in the volume and weight of the testes compared with the contralateral sham‐transplanted testes and/or to the transplanted testes of the radiation‐only monkeys; (ii) increases in TDI compared to the transplanted testes of radiation‐only monkeys at 24 weeks (9.6% vs. 2.9%; p = 0.05) and 44 weeks (16.5% vs. 6.1%, p = 0.055); (iii) detection of lentiviral sequences in the spermatozoa or testes of five of the GnRH‐ant–treated monkeys and (iv) significantly higher sperm counts than in the radiation‐only monkeys. Thus hormone suppression enhances spermatogenic recovery from transplanted SSC in primates and may be a useful tool in conjunction with spermatogonial transplantation to restore fertility in men after cancer treatment.</description><identifier>ISSN: 2047-2919</identifier><identifier>EISSN: 2047-2927</identifier><identifier>DOI: 10.1111/j.2047-2927.2013.00126.x</identifier><identifier>PMID: 24124124</identifier><language>eng</language><publisher>Schaumburg, IL: American Society of Andrology</publisher><subject>Animals ; Biological and medical sciences ; Birth control ; Fundamental and applied biological sciences. Psychology ; Germ Cells - transplantation ; Gonadotropin-Releasing Hormone - antagonists & inhibitors ; gonadotropin‐releasing hormone‐antagonist ; Gynecology. Andrology. Obstetrics ; Hormone Antagonists - pharmacology ; infertility ; Macaca fascicularis ; Male ; Male genital diseases ; Mammalian male genital system ; Medical sciences ; Mice ; Oligopeptides - pharmacology ; radiation ; Sperm Count ; spermatogenesis ; Spermatogenesis - drug effects ; Spermatogonia - cytology ; Spermatogonia - transplantation ; Sterility. Assisted procreation ; Testis - cytology ; Testis - radiation effects ; transplantation ; Transplantation, Heterologous ; Vertebrates: reproduction</subject><ispartof>Andrology (Oxford), 2013-11, Vol.1 (6), p.886-898</ispartof><rights>2013 American Society of Andrology and European Academy of Andrology</rights><rights>2014 INIST-CNRS</rights><rights>2013 American Society of Andrology and European Academy of Andrology.</rights><rights>Andrology©2013 American Society of Andrology and European Academy of Andrology</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5326-70497dda134b07860f26a27a73e6d6c3d1ebc06a17e4d79f72f91ce68e62f473</citedby><cites>FETCH-LOGICAL-c5326-70497dda134b07860f26a27a73e6d6c3d1ebc06a17e4d79f72f91ce68e62f473</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fj.2047-2927.2013.00126.x$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fj.2047-2927.2013.00126.x$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>230,314,776,780,881,1411,1427,27903,27904,45553,45554,46388,46812</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=27844687$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24124124$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Shetty, G.</creatorcontrib><creatorcontrib>Uthamanthil, R. K.</creatorcontrib><creatorcontrib>Zhou, W.</creatorcontrib><creatorcontrib>Shao, S. H.</creatorcontrib><creatorcontrib>Weng, C. C.</creatorcontrib><creatorcontrib>Tailor, R. C.</creatorcontrib><creatorcontrib>Hermann, B. P.</creatorcontrib><creatorcontrib>Orwig, K. E.</creatorcontrib><creatorcontrib>Meistrich, M. L.</creatorcontrib><title>Hormone suppression with GnRH antagonist promotes spermatogenic recovery from transplanted spermatogonial stem cells in irradiated cynomolgus monkeys</title><title>Andrology (Oxford)</title><addtitle>Andrology</addtitle><description>Summary
Hormone suppression given before or after cytotoxic treatment stimulates the recovery of spermatogenesis from endogenous and transplanted spermatogonial stem cells (SSC) and restores fertility in rodents. To test whether the combination of hormone suppression and transplantation could enhance the recovery of spermatogenesis in primates, we irradiated (7 Gy) the testes of 12 adult cynomolgus monkeys and treated six of them with gonadotropin‐releasing hormone antagonist (GnRH‐ant) for 8 weeks. At the end of this treatment, we transfected cryopreserved testicular cells with green fluorescent protein‐lentivirus and autologously transplanted them back into one of the testes. The only significant effect of GnRH‐ant treatment on endogenous spermatogenesis was an increase in the percentage of tubules containing differentiated germ cells (tubule differentiation index; TDI) in the sham‐transplanted testes of GnRH‐ant–treated monkeys compared with radiation‐only monkeys at 24 weeks after irradiation. Although transplantation alone after irradiation did not significantly increase the TDI, detection of lentiviral DNA in the spermatozoa of one radiation‐only monkey indicated that some transplanted cells colonized the testis. However, the combination of transplantation and GnRH‐ant clearly stimulated spermatogenic recovery as evidenced by several observations in the GnRH‐ant–treated monkeys receiving transplantation: (i) significant increases (~20%) in the volume and weight of the testes compared with the contralateral sham‐transplanted testes and/or to the transplanted testes of the radiation‐only monkeys; (ii) increases in TDI compared to the transplanted testes of radiation‐only monkeys at 24 weeks (9.6% vs. 2.9%; p = 0.05) and 44 weeks (16.5% vs. 6.1%, p = 0.055); (iii) detection of lentiviral sequences in the spermatozoa or testes of five of the GnRH‐ant–treated monkeys and (iv) significantly higher sperm counts than in the radiation‐only monkeys. Thus hormone suppression enhances spermatogenic recovery from transplanted SSC in primates and may be a useful tool in conjunction with spermatogonial transplantation to restore fertility in men after cancer treatment.</description><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Birth control</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Germ Cells - transplantation</subject><subject>Gonadotropin-Releasing Hormone - antagonists & inhibitors</subject><subject>gonadotropin‐releasing hormone‐antagonist</subject><subject>Gynecology. Andrology. Obstetrics</subject><subject>Hormone Antagonists - pharmacology</subject><subject>infertility</subject><subject>Macaca fascicularis</subject><subject>Male</subject><subject>Male genital diseases</subject><subject>Mammalian male genital system</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Oligopeptides - pharmacology</subject><subject>radiation</subject><subject>Sperm Count</subject><subject>spermatogenesis</subject><subject>Spermatogenesis - drug effects</subject><subject>Spermatogonia - cytology</subject><subject>Spermatogonia - transplantation</subject><subject>Sterility. Assisted procreation</subject><subject>Testis - cytology</subject><subject>Testis - radiation effects</subject><subject>transplantation</subject><subject>Transplantation, Heterologous</subject><subject>Vertebrates: reproduction</subject><issn>2047-2919</issn><issn>2047-2927</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNUV1v1DAQjBCIVqV_AVlCPN7hL-zkAaSqQA-pKlLVd8vnbK4-Ejt4k7b5IfxfnN5xLW-sVvJKMzsee4qCMLpkuT5sl5xKveAV13liYkkp42r58KI4PgAvDzOrjopTxC3NVc7NXxdHXLLHPi5-r2LqYgCCY98nQPQxkHs_3JKLcL0iNgx2E4PHgfQpdnEAJNhD6uwQNxC8IwlcvIM0kSbjZEg2YN_mNaifiFnAtgQH6IiDtkXiA_Ep2drbmeemkKXbzYgkW_kJE74pXjW2RTjdnyfFzbevN-erxeWPi-_nZ5cL91FwtdBUVrquLRNyTXWpaMOV5dpqAapWTtQM1o4qyzTIWleN5k3FHKgSFG-kFifF551sP647qB2E7L81ffKdTZOJ1pt_keBvzSbeGVGWlRJlFni3F0jx1wg4mG0cU8iWDcs451xSlVnljuVSREzQHG5g1MyRmq2Z0zJzcmaO1DxGah7y6tvnDg-LfwPMhPd7gkVn2yb_v_P4xNOllKqcn_ppx7v3LUz_bcCcXX25zpP4Aypywgw</recordid><startdate>201311</startdate><enddate>201311</enddate><creator>Shetty, G.</creator><creator>Uthamanthil, R. K.</creator><creator>Zhou, W.</creator><creator>Shao, S. H.</creator><creator>Weng, C. C.</creator><creator>Tailor, R. C.</creator><creator>Hermann, B. P.</creator><creator>Orwig, K. E.</creator><creator>Meistrich, M. L.</creator><general>American Society of Andrology</general><general>Wiley Subscription Services, Inc</general><scope>IQODW</scope><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>K9.</scope><scope>5PM</scope></search><sort><creationdate>201311</creationdate><title>Hormone suppression with GnRH antagonist promotes spermatogenic recovery from transplanted spermatogonial stem cells in irradiated cynomolgus monkeys</title><author>Shetty, G. ; Uthamanthil, R. K. ; Zhou, W. ; Shao, S. H. ; Weng, C. C. ; Tailor, R. C. ; Hermann, B. P. ; Orwig, K. E. ; Meistrich, M. L.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5326-70497dda134b07860f26a27a73e6d6c3d1ebc06a17e4d79f72f91ce68e62f473</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Birth control</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Germ Cells - transplantation</topic><topic>Gonadotropin-Releasing Hormone - antagonists & inhibitors</topic><topic>gonadotropin‐releasing hormone‐antagonist</topic><topic>Gynecology. Andrology. Obstetrics</topic><topic>Hormone Antagonists - pharmacology</topic><topic>infertility</topic><topic>Macaca fascicularis</topic><topic>Male</topic><topic>Male genital diseases</topic><topic>Mammalian male genital system</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Oligopeptides - pharmacology</topic><topic>radiation</topic><topic>Sperm Count</topic><topic>spermatogenesis</topic><topic>Spermatogenesis - drug effects</topic><topic>Spermatogonia - cytology</topic><topic>Spermatogonia - transplantation</topic><topic>Sterility. Assisted procreation</topic><topic>Testis - cytology</topic><topic>Testis - radiation effects</topic><topic>transplantation</topic><topic>Transplantation, Heterologous</topic><topic>Vertebrates: reproduction</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Shetty, G.</creatorcontrib><creatorcontrib>Uthamanthil, R. K.</creatorcontrib><creatorcontrib>Zhou, W.</creatorcontrib><creatorcontrib>Shao, S. H.</creatorcontrib><creatorcontrib>Weng, C. C.</creatorcontrib><creatorcontrib>Tailor, R. C.</creatorcontrib><creatorcontrib>Hermann, B. P.</creatorcontrib><creatorcontrib>Orwig, K. E.</creatorcontrib><creatorcontrib>Meistrich, M. L.</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Andrology (Oxford)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Shetty, G.</au><au>Uthamanthil, R. K.</au><au>Zhou, W.</au><au>Shao, S. H.</au><au>Weng, C. C.</au><au>Tailor, R. C.</au><au>Hermann, B. P.</au><au>Orwig, K. E.</au><au>Meistrich, M. L.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Hormone suppression with GnRH antagonist promotes spermatogenic recovery from transplanted spermatogonial stem cells in irradiated cynomolgus monkeys</atitle><jtitle>Andrology (Oxford)</jtitle><addtitle>Andrology</addtitle><date>2013-11</date><risdate>2013</risdate><volume>1</volume><issue>6</issue><spage>886</spage><epage>898</epage><pages>886-898</pages><issn>2047-2919</issn><eissn>2047-2927</eissn><abstract>Summary
Hormone suppression given before or after cytotoxic treatment stimulates the recovery of spermatogenesis from endogenous and transplanted spermatogonial stem cells (SSC) and restores fertility in rodents. To test whether the combination of hormone suppression and transplantation could enhance the recovery of spermatogenesis in primates, we irradiated (7 Gy) the testes of 12 adult cynomolgus monkeys and treated six of them with gonadotropin‐releasing hormone antagonist (GnRH‐ant) for 8 weeks. At the end of this treatment, we transfected cryopreserved testicular cells with green fluorescent protein‐lentivirus and autologously transplanted them back into one of the testes. The only significant effect of GnRH‐ant treatment on endogenous spermatogenesis was an increase in the percentage of tubules containing differentiated germ cells (tubule differentiation index; TDI) in the sham‐transplanted testes of GnRH‐ant–treated monkeys compared with radiation‐only monkeys at 24 weeks after irradiation. Although transplantation alone after irradiation did not significantly increase the TDI, detection of lentiviral DNA in the spermatozoa of one radiation‐only monkey indicated that some transplanted cells colonized the testis. However, the combination of transplantation and GnRH‐ant clearly stimulated spermatogenic recovery as evidenced by several observations in the GnRH‐ant–treated monkeys receiving transplantation: (i) significant increases (~20%) in the volume and weight of the testes compared with the contralateral sham‐transplanted testes and/or to the transplanted testes of the radiation‐only monkeys; (ii) increases in TDI compared to the transplanted testes of radiation‐only monkeys at 24 weeks (9.6% vs. 2.9%; p = 0.05) and 44 weeks (16.5% vs. 6.1%, p = 0.055); (iii) detection of lentiviral sequences in the spermatozoa or testes of five of the GnRH‐ant–treated monkeys and (iv) significantly higher sperm counts than in the radiation‐only monkeys. Thus hormone suppression enhances spermatogenic recovery from transplanted SSC in primates and may be a useful tool in conjunction with spermatogonial transplantation to restore fertility in men after cancer treatment.</abstract><cop>Schaumburg, IL</cop><pub>American Society of Andrology</pub><pmid>24124124</pmid><doi>10.1111/j.2047-2927.2013.00126.x</doi><tpages>13</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Biological and medical sciences Birth control Fundamental and applied biological sciences. Psychology Germ Cells - transplantation Gonadotropin-Releasing Hormone - antagonists & inhibitors gonadotropin‐releasing hormone‐antagonist Gynecology. Andrology. Obstetrics Hormone Antagonists - pharmacology infertility Macaca fascicularis Male Male genital diseases Mammalian male genital system Medical sciences Mice Oligopeptides - pharmacology radiation Sperm Count spermatogenesis Spermatogenesis - drug effects Spermatogonia - cytology Spermatogonia - transplantation Sterility. Assisted procreation Testis - cytology Testis - radiation effects transplantation Transplantation, Heterologous Vertebrates: reproduction |
| title | Hormone suppression with GnRH antagonist promotes spermatogenic recovery from transplanted spermatogonial stem cells in irradiated cynomolgus monkeys |
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