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Published in: Reproductive Biology and Endocrinology 1/2009

Open Access 01-12-2009 | Research

Gene expression profiles of mouse spermatogenesis during recovery from irradiation

Authors: Fozia J Shah, Masami Tanaka, John E Nielsen, Teruaki Iwamoto, Shinichi Kobayashi, Niels E Skakkebæk, Henrik Leffers, Kristian Almstrup

Published in: Reproductive Biology and Endocrinology | Issue 1/2009

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Abstract

Background

Irradiation or chemotherapy that suspend normal spermatogenesis is commonly used to treat various cancers. Fortunately, spermatogenesis in many cases can be restored after such treatments but knowledge is limited about the re-initiation process. Earlier studies have described the cellular changes that happen during recovery from irradiation by means of histology. We have earlier generated gene expression profiles during induction of spermatogenesis in mouse postnatal developing testes and found a correlation between profiles and the expressing cell types. The aim of the present work was to utilize the link between expression profile and cell types to follow the cellular changes that occur during post-irradiation recovery of spermatogenesis in order to describe recovery by means of gene expression.

Methods

Adult mouse testes were subjected to irradiation with 1 Gy or a fractionated radiation of two times 1 Gy. Testes were sampled every third or fourth day to follow the recovery of spermatogenesis and gene expression profiles generated by means of differential display RT-PCR. In situ hybridization was in addition performed to verify cell-type specific gene expression patterns.

Results

Irradiation of mice testis created a gap in spermatogenesis, which was initiated by loss of A1 to B-spermatogonia and lasted for approximately 10 days. Irradiation with 2 times 1 Gy showed a more pronounced effect on germ cell elimination than with 1 Gy, but spermatogenesis was in both cases completely reconstituted 42 days after irradiation. Comparison of expression profiles indicated that the cellular reconstitution appeared equivalent to what is observed during induction of normal spermatogenesis.

Conclusion

The data indicates that recovery of spermatogenesis can be monitored by means of gene expression, which could aid in designing radiation treatment regimes for cancer patients leading to better restoration of spermatogenesis.
Appendix
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Literature
1.
go back to reference Efstathiou E, Logothetis C: Review of late complications of treatment and late relapse in testicular cancer. J Natl Compr Canc Netw. 2006, 4 (10): 1059-1070.PubMed Efstathiou E, Logothetis C: Review of late complications of treatment and late relapse in testicular cancer. J Natl Compr Canc Netw. 2006, 4 (10): 1059-1070.PubMed
2.
go back to reference Russell L, Ettlin R, Sinha Hikim A, Clegg E: Histological and histopathological evaluation of the testis. 1990, Clearwater, FL: Cache River Press, 1 Russell L, Ettlin R, Sinha Hikim A, Clegg E: Histological and histopathological evaluation of the testis. 1990, Clearwater, FL: Cache River Press, 1
3.
go back to reference Meistrich M: Effects of chemotherapy and radiotherapy on spermatogenesis. Eur Urol. 1993, 23 (1): 136-141.PubMed Meistrich M: Effects of chemotherapy and radiotherapy on spermatogenesis. Eur Urol. 1993, 23 (1): 136-141.PubMed
4.
go back to reference Shetty G, Meistrich M: Hormonal approaches to preservation and restoration of male fertility after cancer treatment. J Natl Cancer Inst Monogr. 2005, 36-39. 10.1093/jncimonographs/lgi002. 34 Shetty G, Meistrich M: Hormonal approaches to preservation and restoration of male fertility after cancer treatment. J Natl Cancer Inst Monogr. 2005, 36-39. 10.1093/jncimonographs/lgi002. 34
5.
go back to reference Fosså S, Magelssen H: Fertility and reproduction after chemotherapy of adult cancer patients: malignant lymphoma and testicular cancer. Ann Oncol. 2004, 15 (Suppl 4): iv259-265.PubMed Fosså S, Magelssen H: Fertility and reproduction after chemotherapy of adult cancer patients: malignant lymphoma and testicular cancer. Ann Oncol. 2004, 15 (Suppl 4): iv259-265.PubMed
6.
go back to reference de Rooij D, Russell L: All you wanted to know about spermatogonia but were afraid to ask. J Androl. 2000, 21 (6): 776-798.PubMed de Rooij D, Russell L: All you wanted to know about spermatogonia but were afraid to ask. J Androl. 2000, 21 (6): 776-798.PubMed
7.
go back to reference Huckins C: The spermatogonial stem cell population in adult rats. I. Their morphology, proliferation and maturation. Anat Rec. 1971, 169 (3): 533-557. 10.1002/ar.1091690306.CrossRefPubMed Huckins C: The spermatogonial stem cell population in adult rats. I. Their morphology, proliferation and maturation. Anat Rec. 1971, 169 (3): 533-557. 10.1002/ar.1091690306.CrossRefPubMed
8.
go back to reference Sharpe R: Regulation of spermatogenesis. The Physiology of Reproduction. Edited by: Knobil EaN JD. 1994, New York: Raven Press, Inc, 1363-1434. 2 Sharpe R: Regulation of spermatogenesis. The Physiology of Reproduction. Edited by: Knobil EaN JD. 1994, New York: Raven Press, Inc, 1363-1434. 2
9.
go back to reference Oakberg E: A description of spermiogenesis in the mouse and its use in analysis of the cycle of the seminiferous epithelium and germ cell renewal. Am J Anat. 1956, 99 (3): 391-413. 10.1002/aja.1000990303.CrossRefPubMed Oakberg E: A description of spermiogenesis in the mouse and its use in analysis of the cycle of the seminiferous epithelium and germ cell renewal. Am J Anat. 1956, 99 (3): 391-413. 10.1002/aja.1000990303.CrossRefPubMed
10.
go back to reference Oakberg E: Gamma-ray sensitivity of spermatogonia of the mouse. J Exp Zool. 1957, 134 (2): 343-356. 10.1002/jez.1401340208.CrossRefPubMed Oakberg E: Gamma-ray sensitivity of spermatogonia of the mouse. J Exp Zool. 1957, 134 (2): 343-356. 10.1002/jez.1401340208.CrossRefPubMed
11.
go back to reference Oakberg E: Initial depletion and subsequent recovery of spermatogonia of the mouse after 20 r of gamma rays and 100, 300, and 600 r of x-rays. Radiat Res. 1959, 11: 700-719. 10.2307/3570749.CrossRefPubMed Oakberg E: Initial depletion and subsequent recovery of spermatogonia of the mouse after 20 r of gamma rays and 100, 300, and 600 r of x-rays. Radiat Res. 1959, 11: 700-719. 10.2307/3570749.CrossRefPubMed
12.
go back to reference Meistrich M: Quantitative correlation between testicular stem cell survival, sperm production, and fertility in the mouse after treatment with different cytotoxic agents. J Androl. 1982, 3: 58-68. Meistrich M: Quantitative correlation between testicular stem cell survival, sperm production, and fertility in the mouse after treatment with different cytotoxic agents. J Androl. 1982, 3: 58-68.
13.
go back to reference Meistrich M, Wilson G, Mathur K, Fuller L, Rodriguez M, McLaughlin P, Romaguera J, Cabanillas F, Ha C, Lipshultz L, Hagemeister FB: Rapid recovery of spermatogenesis after mitoxantrone, vincristine, vinblastine, and prednisone chemotherapy for Hodgkin's disease. J Clin Oncol. 1997, 15 (12): 3488-3495.PubMed Meistrich M, Wilson G, Mathur K, Fuller L, Rodriguez M, McLaughlin P, Romaguera J, Cabanillas F, Ha C, Lipshultz L, Hagemeister FB: Rapid recovery of spermatogenesis after mitoxantrone, vincristine, vinblastine, and prednisone chemotherapy for Hodgkin's disease. J Clin Oncol. 1997, 15 (12): 3488-3495.PubMed
14.
go back to reference Meer van der Y, Huiskamp R, Davids J, Tweel van der I, de Rooij D: The sensitivity of quiescent and proliferating mouse spermatogonial stem cells to X irradiation. Radiat Res. 1992, 130 (3): 289-295. 10.2307/3578373.CrossRefPubMed Meer van der Y, Huiskamp R, Davids J, Tweel van der I, de Rooij D: The sensitivity of quiescent and proliferating mouse spermatogonial stem cells to X irradiation. Radiat Res. 1992, 130 (3): 289-295. 10.2307/3578373.CrossRefPubMed
15.
go back to reference Meer van der Y, Huiskamp R, Davids J, Tweel van der I, de Rooij D: The sensitivity to X rays of mouse spermatogonia that are committed to differentiate and of differentiating spermatogonia. Radiat Res. 1992, 130 (3): 296-302. 10.2307/3578374.CrossRefPubMed Meer van der Y, Huiskamp R, Davids J, Tweel van der I, de Rooij D: The sensitivity to X rays of mouse spermatogonia that are committed to differentiate and of differentiating spermatogonia. Radiat Res. 1992, 130 (3): 296-302. 10.2307/3578374.CrossRefPubMed
16.
go back to reference Dym M, Clermont Y: Role of spermatogonia in the repair of the seminiferous epithelium following x-irradiation of the rat testis. Am J Anat. 1970, 128 (3): 265-282. 10.1002/aja.1001280302.CrossRefPubMed Dym M, Clermont Y: Role of spermatogonia in the repair of the seminiferous epithelium following x-irradiation of the rat testis. Am J Anat. 1970, 128 (3): 265-282. 10.1002/aja.1001280302.CrossRefPubMed
17.
go back to reference Pinon-Lataillade G, Maas J: Continuous gamma-irradiation of rats: dose-rate effect on loss and recovery of spermatogenesis. Strahlentherapie. 1985, 161 (7): 421-426.PubMed Pinon-Lataillade G, Maas J: Continuous gamma-irradiation of rats: dose-rate effect on loss and recovery of spermatogenesis. Strahlentherapie. 1985, 161 (7): 421-426.PubMed
18.
go back to reference Bustos-Obregón E, Rodriguez H: Testicular x-ray irradiation in adult mice as a model to study spermatogonial proliferation. Andrologia. 1991, 23 (6): 447-450.CrossRefPubMed Bustos-Obregón E, Rodriguez H: Testicular x-ray irradiation in adult mice as a model to study spermatogonial proliferation. Andrologia. 1991, 23 (6): 447-450.CrossRefPubMed
19.
go back to reference West A, Lähdetie J: X-irradiation--induced changes in the progression of type B spermatogonia and preleptotene spermatocytes. Mol Reprod Dev. 2001, 58 (1): 78-87. 10.1002/1098-2795(200101)58:1<78::AID-MRD11>3.0.CO;2-J.CrossRefPubMed West A, Lähdetie J: X-irradiation--induced changes in the progression of type B spermatogonia and preleptotene spermatocytes. Mol Reprod Dev. 2001, 58 (1): 78-87. 10.1002/1098-2795(200101)58:1<78::AID-MRD11>3.0.CO;2-J.CrossRefPubMed
20.
go back to reference Withers H, Hunter N, Barkley HJ, Reid B: Radiation survival and regeneration characteristics of spermatogenic stem cells of mouse testis. Radiat Res. 1974, 57 (1): 88-103. 10.2307/3573759.CrossRefPubMed Withers H, Hunter N, Barkley HJ, Reid B: Radiation survival and regeneration characteristics of spermatogenic stem cells of mouse testis. Radiat Res. 1974, 57 (1): 88-103. 10.2307/3573759.CrossRefPubMed
21.
go back to reference Meistrich M: Critical components of testicular function and sensitivity to disruption. Biol Reprod. 1986, 34 (1): 17-28. 10.1095/biolreprod34.1.17.CrossRefPubMed Meistrich M: Critical components of testicular function and sensitivity to disruption. Biol Reprod. 1986, 34 (1): 17-28. 10.1095/biolreprod34.1.17.CrossRefPubMed
22.
go back to reference van Beek M, Meistrich M, de Rooij D: Probability of self-renewing divisions of spermatogonial stem cells in colonies, formed after fission neutron irradiation. Cell Tissue Kinet. 1990, 23 (1): 1-16.PubMed van Beek M, Meistrich M, de Rooij D: Probability of self-renewing divisions of spermatogonial stem cells in colonies, formed after fission neutron irradiation. Cell Tissue Kinet. 1990, 23 (1): 1-16.PubMed
23.
go back to reference Mian T, Suzuki N, Glenn H, Haynie T, Meistrich M: Radiation damage to mouse testis cells from [99 mTc] pertechnetate. J Nucl Med. 1977, 18 (11): 1116-1122.PubMed Mian T, Suzuki N, Glenn H, Haynie T, Meistrich M: Radiation damage to mouse testis cells from [99 mTc] pertechnetate. J Nucl Med. 1977, 18 (11): 1116-1122.PubMed
24.
go back to reference Meistrich M, Trostle P, Frapart M, Erickson R: Biosynthesis and localization of lactate dehydrogenase X in pachytene spermatocytes and spermatids of mouse testes. Dev Biol. 1977, 60 (2): 428-441. 10.1016/0012-1606(77)90140-3.CrossRefPubMed Meistrich M, Trostle P, Frapart M, Erickson R: Biosynthesis and localization of lactate dehydrogenase X in pachytene spermatocytes and spermatids of mouse testes. Dev Biol. 1977, 60 (2): 428-441. 10.1016/0012-1606(77)90140-3.CrossRefPubMed
25.
go back to reference Kreuser E, Kurrle E, Hetzel W, Heymer B, Porzsolt F, Hautmann R, Gaus W, Schlipf U, Pfeiffer E, Heimpel H: [Reversible germ cell toxicity following aggressive chemotherapy in patients with testicular tumors: results of a prospective study]. Klin Wochenschr. 1989, 67 (7): 367-378. 10.1007/BF01711264.CrossRefPubMed Kreuser E, Kurrle E, Hetzel W, Heymer B, Porzsolt F, Hautmann R, Gaus W, Schlipf U, Pfeiffer E, Heimpel H: [Reversible germ cell toxicity following aggressive chemotherapy in patients with testicular tumors: results of a prospective study]. Klin Wochenschr. 1989, 67 (7): 367-378. 10.1007/BF01711264.CrossRefPubMed
26.
go back to reference Kangasniemi M, Cheng C, Toppari J, Grima J, Stahler M, Bardin C, Parvinen M: Basal and FSH-stimulated steady state levels of SGP-2, alpha 2-macroglobulin, and testibumin in culture media of rat seminiferous tubules at defined stages of the epithelial cycle. J Androl. 1992, 13 (3): 208-213.PubMed Kangasniemi M, Cheng C, Toppari J, Grima J, Stahler M, Bardin C, Parvinen M: Basal and FSH-stimulated steady state levels of SGP-2, alpha 2-macroglobulin, and testibumin in culture media of rat seminiferous tubules at defined stages of the epithelial cycle. J Androl. 1992, 13 (3): 208-213.PubMed
27.
go back to reference Rowley M, Leach D, Warner G, Heller C: Effect of graded doses of ionizing radiation on the human testis. Radiat Res. 1974, 59 (3): 665-678. 10.2307/3574084.CrossRefPubMed Rowley M, Leach D, Warner G, Heller C: Effect of graded doses of ionizing radiation on the human testis. Radiat Res. 1974, 59 (3): 665-678. 10.2307/3574084.CrossRefPubMed
28.
go back to reference Meistrich M, Wilson G, Brown B, da Cunha M, Lipshultz L: Impact of cyclophosphamide on long-term reduction in sperm count in men treated with combination chemotherapy for Ewing and soft tissue sarcomas. Cancer. 1992, 70 (11): 2703-2712. 10.1002/1097-0142(19921201)70:11<2703::AID-CNCR2820701123>3.0.CO;2-X.CrossRefPubMed Meistrich M, Wilson G, Brown B, da Cunha M, Lipshultz L: Impact of cyclophosphamide on long-term reduction in sperm count in men treated with combination chemotherapy for Ewing and soft tissue sarcomas. Cancer. 1992, 70 (11): 2703-2712. 10.1002/1097-0142(19921201)70:11<2703::AID-CNCR2820701123>3.0.CO;2-X.CrossRefPubMed
29.
go back to reference Zhang Z, Shao S, Meistrich M: The radiation-induced block in spermatogonial differentiation is due to damage to the somatic environment, not the germ cells. J Cell Physiol. 2007, 211 (1): 149-158. 10.1002/jcp.20910.CrossRefPubMed Zhang Z, Shao S, Meistrich M: The radiation-induced block in spermatogonial differentiation is due to damage to the somatic environment, not the germ cells. J Cell Physiol. 2007, 211 (1): 149-158. 10.1002/jcp.20910.CrossRefPubMed
30.
go back to reference Zhang Z, Shao S, Shetty G, Meistrich M: Donor Sertoli cells transplanted into irradiated rat testes stimulate partial recovery of endogenous spermatogenesis. Reproduction. 2009, 137 (3): 497-508. 10.1530/REP-08-0120.CrossRefPubMed Zhang Z, Shao S, Shetty G, Meistrich M: Donor Sertoli cells transplanted into irradiated rat testes stimulate partial recovery of endogenous spermatogenesis. Reproduction. 2009, 137 (3): 497-508. 10.1530/REP-08-0120.CrossRefPubMed
31.
go back to reference Porter K, Shetty G, Shuttlesworth G, Weng C, Huhtaniemi I, Pakarinen P, Meistrich M: Estrogen Enhances Recovery from Radiation-Induced Spermatogonial Arrest in Rat Testes. J Androl. 2009, Porter K, Shetty G, Shuttlesworth G, Weng C, Huhtaniemi I, Pakarinen P, Meistrich M: Estrogen Enhances Recovery from Radiation-Induced Spermatogonial Arrest in Rat Testes. J Androl. 2009,
32.
go back to reference Jørgensen M, Bévort M, Kledal T, Hansen B, Dalgaard M, Leffers H: Differential display competitive polymerase chain reaction: an optimal tool for assaying gene expression. Electrophoresis. 1999, 20 (2): 230-240.CrossRefPubMed Jørgensen M, Bévort M, Kledal T, Hansen B, Dalgaard M, Leffers H: Differential display competitive polymerase chain reaction: an optimal tool for assaying gene expression. Electrophoresis. 1999, 20 (2): 230-240.CrossRefPubMed
33.
go back to reference Nielsen J, Hansen M, Jørgensen M, Tanaka M, Almstrup K, Skakkebaek N, Leffers H: Germ cell differentiation-dependent and stage-specific expression of LANCL1 in rodent testis. Eur J Histochem. 2003, 47 (3): 215-222.CrossRefPubMed Nielsen J, Hansen M, Jørgensen M, Tanaka M, Almstrup K, Skakkebaek N, Leffers H: Germ cell differentiation-dependent and stage-specific expression of LANCL1 in rodent testis. Eur J Histochem. 2003, 47 (3): 215-222.CrossRefPubMed
34.
go back to reference Almstrup K, Nielsen J, Hansen M, Tanaka M, Skakkebaek N, Leffers H: Analysis of cell-type-specific gene expression during mouse spermatogenesis. Biol Reprod. 2004, 70 (6): 1751-1761. 10.1095/biolreprod.103.026575.CrossRefPubMed Almstrup K, Nielsen J, Hansen M, Tanaka M, Skakkebaek N, Leffers H: Analysis of cell-type-specific gene expression during mouse spermatogenesis. Biol Reprod. 2004, 70 (6): 1751-1761. 10.1095/biolreprod.103.026575.CrossRefPubMed
35.
go back to reference Shih D, Kleene K: A study by in situ hybridization of the stage of appearance and disappearance of the transition protein 2 and the mitochondrial capsule seleno-protein mRNAs during spermatogenesis in the mouse. Mol Reprod Dev. 1992, 33 (2): 222-227. 10.1002/mrd.1080330216.CrossRefPubMed Shih D, Kleene K: A study by in situ hybridization of the stage of appearance and disappearance of the transition protein 2 and the mitochondrial capsule seleno-protein mRNAs during spermatogenesis in the mouse. Mol Reprod Dev. 1992, 33 (2): 222-227. 10.1002/mrd.1080330216.CrossRefPubMed
36.
go back to reference Hansen M, Nielsen J, Tanaka M, Almstrup K, Skakkebaek N, Leffers H: Identification and expression profiling of 10 novel spermatid expressed CYPT genes. Mol Reprod Dev. 2006, 73 (5): 568-579. 10.1002/mrd.20463.CrossRefPubMed Hansen M, Nielsen J, Tanaka M, Almstrup K, Skakkebaek N, Leffers H: Identification and expression profiling of 10 novel spermatid expressed CYPT genes. Mol Reprod Dev. 2006, 73 (5): 568-579. 10.1002/mrd.20463.CrossRefPubMed
37.
go back to reference Zhou W, Bolden-Tiller O, Shetty G, Shao S, Weng C, Pakarinen P, Liu Z, Stivers D, Meistrich M: Changes in Gene Expression in Somatic Cells of Rat Testes Resulting from Hormonal Modulation and Radiation-Induced Germ Cell Depletion. Biol Reprod. 2009, Zhou W, Bolden-Tiller O, Shetty G, Shao S, Weng C, Pakarinen P, Liu Z, Stivers D, Meistrich M: Changes in Gene Expression in Somatic Cells of Rat Testes Resulting from Hormonal Modulation and Radiation-Induced Germ Cell Depletion. Biol Reprod. 2009,
38.
go back to reference Huang W, Lin Y, Hsiao K, Eilber K, Salido E, Yen P: Restricted expression of the human DAZ protein in premeiotic germ cells. Hum Reprod. 2008, 23 (6): 1280-1289. 10.1093/humrep/den099.PubMedCentralCrossRefPubMed Huang W, Lin Y, Hsiao K, Eilber K, Salido E, Yen P: Restricted expression of the human DAZ protein in premeiotic germ cells. Hum Reprod. 2008, 23 (6): 1280-1289. 10.1093/humrep/den099.PubMedCentralCrossRefPubMed
39.
go back to reference Bellvé A, Millette C, Bhatnagar Y, O'Brien D: Dissociation of the mouse testis and characterization of isolated spermatogenic cells. J Histochem Cytochem. 1977, 25 (7): 480-494.CrossRefPubMed Bellvé A, Millette C, Bhatnagar Y, O'Brien D: Dissociation of the mouse testis and characterization of isolated spermatogenic cells. J Histochem Cytochem. 1977, 25 (7): 480-494.CrossRefPubMed
40.
go back to reference Ivell R, Spiess A: Analysing Differential Gene Expression in the Testis. Testicular Tangrams. Edited by: Rommerts F, Teerds K. 2002, Heidelberg: Springer, 99-120. Workshop Supplement 9 Ivell R, Spiess A: Analysing Differential Gene Expression in the Testis. Testicular Tangrams. Edited by: Rommerts F, Teerds K. 2002, Heidelberg: Springer, 99-120. Workshop Supplement 9
Metadata
Title
Gene expression profiles of mouse spermatogenesis during recovery from irradiation
Authors
Fozia J Shah
Masami Tanaka
John E Nielsen
Teruaki Iwamoto
Shinichi Kobayashi
Niels E Skakkebæk
Henrik Leffers
Kristian Almstrup
Publication date
01-12-2009
Publisher
BioMed Central
Published in
Reproductive Biology and Endocrinology / Issue 1/2009
Electronic ISSN: 1477-7827
DOI
https://doi.org/10.1186/1477-7827-7-130

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