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Effects of Orchiopexy on Congenitally Cryptorchid Insulin-3 Knockout Mice

睾丸激素 医学 精子发生 睾丸萎缩 小袋 不育 精子 外科 男科 生物 怀孕 遗传学
作者
Michael Nguyen,Patrick R. Showalter,Charles F. Timmons,Serge Nef,Luis F. Parada,Linda A. Baker
出处
期刊:The Journal of Urology [Lippincott Williams & Wilkins]
卷期号:168 (4 Part 2): 1779-1783 被引量:38
标识
DOI:10.1016/s0022-5347(05)64412-6
摘要

No AccessJournal of UrologyBasic Science1 Oct 2002Effects of Orchiopexy on Congenitally Cryptorchid Insulin-3 Knockout Mice Michael T. Nguyen, Patrick R. Showalter, Charles F. Timmons, Serge Nef, Luis F. Parada, and Linda A. Baker Michael T. NguyenMichael T. Nguyen , Patrick R. ShowalterPatrick R. Showalter , Charles F. TimmonsCharles F. Timmons , Serge NefSerge Nef , Luis F. ParadaLuis F. Parada , and Linda A. BakerLinda A. Baker View All Author Informationhttps://doi.org/10.1016/S0022-5347(05)64412-6AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: Insulin-3 (Insl3) knockout mice exhibit isolated, bilateral, high intra-abdominal cryptorchidism. If left in this position until adulthood, these testes will deteriorate to the Sertoli-cell-only state, leading to infertility in 100%. We examined the effect of orchiopexy in this genetically engineered animal model. Materials and Methods: A total of 160 testes from 80 male offspring of Insl3 F1 crosses underwent either no orchiopexy (29 testes), sham surgery (25 testes), 1-stage Fowler-Stephens scrotal orchiopexy (57 testes) or primary orchiopexy into a low abdominal, subcutaneous pouch (49 testes). A group of postoperative mice underwent fertility testing 3 months postoperatively. At 6 to 9 months postoperatively the testes were harvested and histologically analyzed. Results: Testes were atrophic in 100% (25 of 25) of the sham group, 91% (52 of 57) of the Fowler-Stephens orchiopexy group and 33% (16 of 49) of the subcutaneous pouch group (testis weight less than 50 mg.). Fertility testing was done in 30 mice (sham 5, Fowler-Stephens orchiopexy 17 and subcutaneous pouch 8). Infertility was secondary to bilateral testicular atrophy (sham 5 of 5, Fowler-Stephens orchiopexy 13 of 17), spermatogenic maturation arrest (subcutaneous pouch 8 of 8) and ductal obstruction [normal spermatogenesis with epididymis devoid of sperm] (Fowler-Stephens orchiopexy 2 of 17). Fertility with normal spermatogenesis was observed in 2 of 17 Fowler-Stephens orchiopexy mice, both of which were Insl3 knockout mice. Conclusions: Intrascrotal orchiopexy can rescue these congenitally cryptorchid Insl3 knockout testes from their intra-abdominal fate of Sertoli-cell-only and lead to fertility. The results suggest that orchiopexy has a crucial and central role in preservation of spermatogenesis. References 1 : Hormonal control of testicular descent and the cause of cryptorchidism. Reprod Fertil Dev1994; 6: 151. Google Scholar 2 : From malformations to molecular mechanisms in the male: three decades of research on endocrine disrupters. APMIS2001; 109: 263. Google Scholar 3 : Fertility in cryptorchidism: further development of an experimental model. J Urol1987; 137: 128. Link, Google Scholar 4 : Fertility after cryptorchidism: a comparative analysis of early orchidopexy with and without concomitant hormonal therapy in the young male rat. J Urol1994; 151: 227. Link, Google Scholar 5 : Experimental cryptorchidism induces testicular germ cell apoptosis by p53-dependent and -independent pathways in mice. Biol Reprod1998; 58: 492. Google Scholar 6 : Effect of cryptorchidism on testicular histology in a naturally cryptorchid animal model. J Urol1997; 158: 1978. Link, Google Scholar 7 : Cryptorchidism and homeotic transformations of spinal nerves and vertebra in Hoxa-10 mutant mice. Proc Natl Acad Sci USA1995; 92: 8185. Google Scholar 8 : Characterization of Hoxa10/Hoxa11 transheterozygotes reveal functional redundancy and regulatory interactions. Dev Biol2000; 224: 373. Google Scholar 9 : Targeted disruption of the Insl 3 gene causes bilateral cryptorchidism. Mol Endocrinol1999; 13: 681. Google Scholar 10 : Cryptorchidism in mice mutant for Insl3. Nat Genet1999; 22: 295. Google Scholar 11 : Cryptorchidism. Pediatr Surg Int1987; 2: 132. Google Scholar 12 : Postnatal testicular maldevelopment in unilateral cryptorchidism. J Urol1989; 142: 546. Link, Google Scholar 13 Hadziselimovic F. Embryology of testicular descent and maldescent. In: Cryptorchidism: Management and Implications. New York: Springer Verlag, pp. 11–34, 1983 Google Scholar 14 : Surgical management of undescended testis: retrospective study of potential fertility in 274 cases. J Urol1989; 142: 749. Link, Google Scholar 15 : Arrest of spermatogonial differentiation in jsd/jsd, Sl17h/Sl17h, and cryptorchid mice. Biol Reprod1999; 61: 842. Google Scholar 16 : Functional analysis of spermatogonial stem cells in Steel and cryptorchid infertile mouse models. Dev Biol2000; 220: 401. Google Scholar 17 : The natural course of cryptorchidism in rats and the efficacy of orchidopexy or orchidectomy in its treatment before and after puberty. J Pediatr Surg1992; 27: 870. Google Scholar 18 : A molecular basis for estrogen-induced cryptorchidism. Dev Biol2000; 224: 354. Google Scholar 19 : Effects of simulated Fowler-Stephens orchiopexy on testicular structure and function in rats. Am Surg1992; 58: 153. Google Scholar 20 : Fertility after simulated Fowler-Stephens orchiopexy in rats. Am J Surg1992; 163: 270. Google Scholar From the Department of Urology, the Center for Developmental Biology and the Department of Pathology, University of Texas Southwestern Medical Center, Dallas, Texas© 2002 by American Urological Association, Inc.FiguresReferencesRelatedDetailsCited byMizuno K, Hayashi Y, Kojima Y, Kurokawa S, Sasaki S and Kohri K (2018) Early Orchiopexy Improves Subsequent Testicular Development and Spermatogenesis in the Experimental Cryptorchid Rat ModelJournal of Urology, VOL. 179, NO. 3, (1195-1199), Online publication date: 1-Mar-2008. Volume 168Issue 4 Part 2October 2002Page: 1779-1783 Advertisement Copyright & Permissions© 2002 by American Urological Association, Inc.Keywordscryptorchidismfertility, testismodels, animalMetrics Author Information Michael T. Nguyen More articles by this author Patrick R. Showalter More articles by this author Charles F. Timmons More articles by this author Serge Nef More articles by this author Luis F. Parada More articles by this author Linda A. Baker More articles by this author Expand All Advertisement PDF downloadLoading ...

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