Surgically Induced Cryptorchidism-Related Degenerative Changes in Spermatogonia Are Associated with Loss of Cyclic Adenosine Monophosphate-Dependent Phosphodiesterases Type 4 in Abdominal Testes of Rats

The present study was undertaken to investigate the role of phosphodiesterase type 4 (PDE4) enzymes in cryptorchidism-induced apoptosis of the germ cells. Regulation of expression of PDE4 enzymes was studied in the abdominal and scrotal testes of surgically induced cryptorchid rats for 10, 20, and 3...

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Veröffentlicht in:Biology of reproduction 2001-06, Vol.64 (6), p.1583-1589
Hauptverfasser: Farooqui, Shakeel M, Al-Bagdadi, Fakhri, Houslay, Miles D, Bolger, Graeme B, Stout, R, Specian, R. D, Cherry, J. A, Conti, M, O'Donnell, James M
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container_end_page 1589
container_issue 6
container_start_page 1583
container_title Biology of reproduction
container_volume 64
creator Farooqui, Shakeel M
Al-Bagdadi, Fakhri
Houslay, Miles D
Bolger, Graeme B
Stout, R
Specian, R. D
Cherry, J. A
Conti, M
O'Donnell, James M
description The present study was undertaken to investigate the role of phosphodiesterase type 4 (PDE4) enzymes in cryptorchidism-induced apoptosis of the germ cells. Regulation of expression of PDE4 enzymes was studied in the abdominal and scrotal testes of surgically induced cryptorchid rats for 10, 20, and 30 days. In some cases orchidopexy was performed after 30 days of cryptorchidism, and rats were allowed to recover for an additional 50 days. Upon histological examination, marked degenerative changes in the epithelial lining of the seminiferous tubules within abdominal testes were observed compared with contralateral control or age-matched sham-operated rats. These changes included degeneration of some spermatogonia, apoptosis of the secondary spermatocytes, incomplete spermatogenesis, and lack of spermatozoa in the lumen. In contrast, contralateral scrotal testes exhibited normal histology. Significant improvement in the regeneration of spermatogonia was observed in rats after 50 days of recovery following orchidopexy. Immunocytochemical examination suggested the presence of PDE4A in germ cells while PDE4B was predominantly expressed on somatic cells. Western blotting using PDE4 subtype-selective antibodies showed the presence of two PDE4A variants (a 109-kDa PDE4A8 and a previously uncharacterized 88-kDa PDE4A variant) and two PDE4B (78-kDa PDE4B2 and 66-kDa PDE4B variant) bands. In unilaterally cryptorchid animals, the abdominal testis showed a time-dependent decrease in both PDE4A8 and 88-kDa PDE4A variants. In contrast, the expression of 66-kDa PDE4B was markedly increased in a time-dependent fashion in abdominal testes of cryptorchid rats. Animals surgically corrected for cryptorchidism and allowed to recover for 50 days exhibited normal expression of both PDE4A and PDE4B variants compared with aged-matched, sham-operated controls. In conclusion, this study suggests that down-regulation of PDE4A variants in cryptorchid testes may play an important role in the degeneration of spermatogonia and increased apoptotic activity in the germ cells.
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These changes included degeneration of some spermatogonia, apoptosis of the secondary spermatocytes, incomplete spermatogenesis, and lack of spermatozoa in the lumen. In contrast, contralateral scrotal testes exhibited normal histology. Significant improvement in the regeneration of spermatogonia was observed in rats after 50 days of recovery following orchidopexy. Immunocytochemical examination suggested the presence of PDE4A in germ cells while PDE4B was predominantly expressed on somatic cells. Western blotting using PDE4 subtype-selective antibodies showed the presence of two PDE4A variants (a 109-kDa PDE4A8 and a previously uncharacterized 88-kDa PDE4A variant) and two PDE4B (78-kDa PDE4B2 and 66-kDa PDE4B variant) bands. In unilaterally cryptorchid animals, the abdominal testis showed a time-dependent decrease in both PDE4A8 and 88-kDa PDE4A variants. In contrast, the expression of 66-kDa PDE4B was markedly increased in a time-dependent fashion in abdominal testes of cryptorchid rats. Animals surgically corrected for cryptorchidism and allowed to recover for 50 days exhibited normal expression of both PDE4A and PDE4B variants compared with aged-matched, sham-operated controls. 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Obstetrics ; Immunohistochemistry ; Male ; Male genital diseases ; Medical sciences ; Non tumoral diseases ; phosphodiesterases ; Rats ; Rats, Sprague-Dawley ; Seminiferous Tubules - pathology ; signal transduction ; spermatogenesis ; Spermatozoa - pathology ; Testis - enzymology</subject><ispartof>Biology of reproduction, 2001-06, Vol.64 (6), p.1583-1589</ispartof><rights>Society for the Study of Reproduction</rights><rights>2001 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-b448t-4164983f352bda38b329d0260c2ffd779d0a0bafcc04a866ea39609a91a0d4c73</citedby><cites>FETCH-LOGICAL-b448t-4164983f352bda38b329d0260c2ffd779d0a0bafcc04a866ea39609a91a0d4c73</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://bioone.org/doi/pdf/10.1095/biolreprod64.6.1583$$EPDF$$P50$$Gbioone$$H</linktopdf><link.rule.ids>315,782,786,26987,27933,27934,52372</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&amp;idt=1085470$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11369582$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Farooqui, Shakeel M</creatorcontrib><creatorcontrib>Al-Bagdadi, Fakhri</creatorcontrib><creatorcontrib>Houslay, Miles D</creatorcontrib><creatorcontrib>Bolger, Graeme B</creatorcontrib><creatorcontrib>Stout, R</creatorcontrib><creatorcontrib>Specian, R. D</creatorcontrib><creatorcontrib>Cherry, J. A</creatorcontrib><creatorcontrib>Conti, M</creatorcontrib><creatorcontrib>O'Donnell, James M</creatorcontrib><title>Surgically Induced Cryptorchidism-Related Degenerative Changes in Spermatogonia Are Associated with Loss of Cyclic Adenosine Monophosphate-Dependent Phosphodiesterases Type 4 in Abdominal Testes of Rats</title><title>Biology of reproduction</title><addtitle>Biol Reprod</addtitle><description>The present study was undertaken to investigate the role of phosphodiesterase type 4 (PDE4) enzymes in cryptorchidism-induced apoptosis of the germ cells. Regulation of expression of PDE4 enzymes was studied in the abdominal and scrotal testes of surgically induced cryptorchid rats for 10, 20, and 30 days. In some cases orchidopexy was performed after 30 days of cryptorchidism, and rats were allowed to recover for an additional 50 days. 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In some cases orchidopexy was performed after 30 days of cryptorchidism, and rats were allowed to recover for an additional 50 days. Upon histological examination, marked degenerative changes in the epithelial lining of the seminiferous tubules within abdominal testes were observed compared with contralateral control or age-matched sham-operated rats. These changes included degeneration of some spermatogonia, apoptosis of the secondary spermatocytes, incomplete spermatogenesis, and lack of spermatozoa in the lumen. In contrast, contralateral scrotal testes exhibited normal histology. Significant improvement in the regeneration of spermatogonia was observed in rats after 50 days of recovery following orchidopexy. Immunocytochemical examination suggested the presence of PDE4A in germ cells while PDE4B was predominantly expressed on somatic cells. Western blotting using PDE4 subtype-selective antibodies showed the presence of two PDE4A variants (a 109-kDa PDE4A8 and a previously uncharacterized 88-kDa PDE4A variant) and two PDE4B (78-kDa PDE4B2 and 66-kDa PDE4B variant) bands. In unilaterally cryptorchid animals, the abdominal testis showed a time-dependent decrease in both PDE4A8 and 88-kDa PDE4A variants. In contrast, the expression of 66-kDa PDE4B was markedly increased in a time-dependent fashion in abdominal testes of cryptorchid rats. Animals surgically corrected for cryptorchidism and allowed to recover for 50 days exhibited normal expression of both PDE4A and PDE4B variants compared with aged-matched, sham-operated controls. In conclusion, this study suggests that down-regulation of PDE4A variants in cryptorchid testes may play an important role in the degeneration of spermatogonia and increased apoptotic activity in the germ cells.</abstract><cop>Madison, WI</cop><pub>Society for the Study of Reproduction</pub><pmid>11369582</pmid><doi>10.1095/biolreprod64.6.1583</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record>
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subjects 3',5'-Cyclic-AMP Phosphodiesterases - analysis
3',5'-Cyclic-AMP Phosphodiesterases - metabolism
Animals
Apoptosis
Biological and medical sciences
Blotting, Western
Contents
Cryptorchidism - etiology
Cryptorchidism - pathology
Cryptorchidism - surgery
cyclic adenosine monophosphate
Cyclic Nucleotide Phosphodiesterases, Type 4
Epithelium - pathology
gametogenesis
gene regulation
Gynecology. Andrology. Obstetrics
Immunohistochemistry
Male
Male genital diseases
Medical sciences
Non tumoral diseases
phosphodiesterases
Rats
Rats, Sprague-Dawley
Seminiferous Tubules - pathology
signal transduction
spermatogenesis
Spermatozoa - pathology
Testis - enzymology
title Surgically Induced Cryptorchidism-Related Degenerative Changes in Spermatogonia Are Associated with Loss of Cyclic Adenosine Monophosphate-Dependent Phosphodiesterases Type 4 in Abdominal Testes of Rats
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