Spermatogenesis arrest caused by conditional deletion of Hsp90α in adult mice
Summary It is controversial whether a functional androgen receptor (AR) on germ cells, including spermatogonia, is essential for their development into sperm and, thus, initiation and maintenance of spermatogenesis. It was recently shown that many spermatocytes underwent apoptosis in the testes of H...
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| Format: | Article |
| Language: | English |
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The Company of Biologists
2012-08-01
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| Series: | Biology Open |
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| Online Access: | http://bio.biologists.org/content/1/10/977 |
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| author | Chiaki Kajiwara Shiho Kondo Shizuha Uda Lei Dai Tomoko Ichiyanagi Tomoki Chiba Satoshi Ishido Takehiko Koji Heiichiro Udono |
| author_facet | Chiaki Kajiwara Shiho Kondo Shizuha Uda Lei Dai Tomoko Ichiyanagi Tomoki Chiba Satoshi Ishido Takehiko Koji Heiichiro Udono |
| author_sort | Chiaki Kajiwara |
| collection | DOAJ |
| description | Summary
It is controversial whether a functional androgen receptor (AR) on germ cells, including spermatogonia, is essential for their development into sperm and, thus, initiation and maintenance of spermatogenesis. It was recently shown that many spermatocytes underwent apoptosis in the testes of Hsp90α KO mice. We had generated Hsp90α KO mice independently and confirmed this phenotype. However, the important question of whether Hsp90α is required to maintain spermatogenesis in adult mice in which testicular maturation is already completed could not be addressed using these conventional KO mice. To answer this question, we generated a tamoxifen-inducible deletion mutant of Hsp90α and found that conditional deletion of Hsp90α in adult mice caused even more severe apoptosis in germ cells beyond the pachytene stage, leading to complete arrest of spermatogenesis and testicular atrophy. Importantly, immunohistochemical analysis revealed that AR expression in WT testis was more evident in spermatogonia than in spermatocytes, whereas its expression was aberrant and ectopic in Hsp90α KO testis, raising the possibility that an AR abnormality in primordial germ cells is involved in spermatogenesis arrest in the Hsp90α KO mice. Our results suggest that the AR, specifically chaperoned by Hsp90α in spermatogonia, is critical for maintenance of established spermatogenesis and for survival of spermatocytes in adult testis, in addition to setting the first wave of spermatogenesis before puberty. |
| first_indexed | 2024-12-17T03:46:10Z |
| format | Article |
| id | doaj.art-220971528993403ead726e068d32cc58 |
| institution | Directory Open Access Journal |
| issn | 2046-6390 |
| language | English |
| last_indexed | 2024-12-17T03:46:10Z |
| publishDate | 2012-08-01 |
| publisher | The Company of Biologists |
| record_format | Article |
| series | Biology Open |
| spelling | doaj.art-220971528993403ead726e068d32cc582022-12-21T22:04:53ZengThe Company of BiologistsBiology Open2046-63902012-08-0111097798210.1242/bio.20126462012646Spermatogenesis arrest caused by conditional deletion of Hsp90α in adult miceChiaki Kajiwara0Shiho Kondo1Shizuha Uda2Lei Dai3Tomoko Ichiyanagi4Tomoki Chiba5Satoshi Ishido6Takehiko Koji7Heiichiro Udono8 Laboratories for Immunochaperones, Research Center for Allergy and Immunology (RCAI), RIKEN Yokohama Institute, Yokohama 230-0045, Japan Department of Histology and Cell Biology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852-8523, Japan Laboratories for Immunochaperones, Research Center for Allergy and Immunology (RCAI), RIKEN Yokohama Institute, Yokohama 230-0045, Japan Department of Histology and Cell Biology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852-8523, Japan Division of Epigenomics, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan University of Tsukuba Graduate School of Life and Environmental Sciences, Tsukuba, Ibaraki 305-8577, Japan Infectious Immunity, Research Center for Allergy and Immunology (RCAI), RIKEN Yokohama Institute, Yokohama 230-0045, Japan Department of Histology and Cell Biology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852-8523, Japan Laboratories for Immunochaperones, Research Center for Allergy and Immunology (RCAI), RIKEN Yokohama Institute, Yokohama 230-0045, Japan Summary It is controversial whether a functional androgen receptor (AR) on germ cells, including spermatogonia, is essential for their development into sperm and, thus, initiation and maintenance of spermatogenesis. It was recently shown that many spermatocytes underwent apoptosis in the testes of Hsp90α KO mice. We had generated Hsp90α KO mice independently and confirmed this phenotype. However, the important question of whether Hsp90α is required to maintain spermatogenesis in adult mice in which testicular maturation is already completed could not be addressed using these conventional KO mice. To answer this question, we generated a tamoxifen-inducible deletion mutant of Hsp90α and found that conditional deletion of Hsp90α in adult mice caused even more severe apoptosis in germ cells beyond the pachytene stage, leading to complete arrest of spermatogenesis and testicular atrophy. Importantly, immunohistochemical analysis revealed that AR expression in WT testis was more evident in spermatogonia than in spermatocytes, whereas its expression was aberrant and ectopic in Hsp90α KO testis, raising the possibility that an AR abnormality in primordial germ cells is involved in spermatogenesis arrest in the Hsp90α KO mice. Our results suggest that the AR, specifically chaperoned by Hsp90α in spermatogonia, is critical for maintenance of established spermatogenesis and for survival of spermatocytes in adult testis, in addition to setting the first wave of spermatogenesis before puberty.http://bio.biologists.org/content/1/10/977Hsp90αSpermatogoniaSpermatogenesisAndrogen receptor |
| spellingShingle | Chiaki Kajiwara Shiho Kondo Shizuha Uda Lei Dai Tomoko Ichiyanagi Tomoki Chiba Satoshi Ishido Takehiko Koji Heiichiro Udono Spermatogenesis arrest caused by conditional deletion of Hsp90α in adult mice Biology Open Hsp90α Spermatogonia Spermatogenesis Androgen receptor |
| title | Spermatogenesis arrest caused by conditional deletion of Hsp90α in adult mice |
| title_full | Spermatogenesis arrest caused by conditional deletion of Hsp90α in adult mice |
| title_fullStr | Spermatogenesis arrest caused by conditional deletion of Hsp90α in adult mice |
| title_full_unstemmed | Spermatogenesis arrest caused by conditional deletion of Hsp90α in adult mice |
| title_short | Spermatogenesis arrest caused by conditional deletion of Hsp90α in adult mice |
| title_sort | spermatogenesis arrest caused by conditional deletion of hsp90α in adult mice |
| topic | Hsp90α Spermatogonia Spermatogenesis Androgen receptor |
| url | http://bio.biologists.org/content/1/10/977 |
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