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Postnatal Germ Cell Development during Mini-Puberty in the Mouse Does Not Require Androgen Receptor: Implications for Managing Cryptorchidism

医学 雄激素受体 生殖细胞 雄激素 内科学 内分泌学 男科 激素 生物 遗传学 前列腺癌 基因 癌症
作者
Ruili Li,Amanda Vannitamby,Jorien Meijer,Bridget R. Southwell,John M. Hutson
出处
期刊:The Journal of Urology [Lippincott Williams & Wilkins]
卷期号:193 (4): 1361-1367 被引量:25
标识
DOI:10.1016/j.juro.2014.10.024
摘要

No AccessJournal of UrologyPediatric Urology1 Apr 2015Postnatal Germ Cell Development during Mini-Puberty in the Mouse Does Not Require Androgen Receptor: Implications for Managing Cryptorchidism Ruili Li, Amanda Vannitamby, Jorien Meijer, Bridget Southwell, and John Hutson Ruili LiRuili Li Douglas Stephens Surgical Research Laboratory, Murdoch Children’s Research Institute, Parkville, Victoria, Australia Department of Pediatrics, University of Melbourne, Parkville, Victoria, Australia More articles by this author , Amanda VannitambyAmanda Vannitamby Douglas Stephens Surgical Research Laboratory, Murdoch Children’s Research Institute, Parkville, Victoria, Australia More articles by this author , Jorien MeijerJorien Meijer Medical School, University of Groningen, Groningen, The Netherlands More articles by this author , Bridget SouthwellBridget Southwell Douglas Stephens Surgical Research Laboratory, Murdoch Children’s Research Institute, Parkville, Victoria, Australia Department of Pediatrics, University of Melbourne, Parkville, Victoria, Australia More articles by this author , and John HutsonJohn Hutson Douglas Stephens Surgical Research Laboratory, Murdoch Children’s Research Institute, Parkville, Victoria, Australia Department of Pediatrics, University of Melbourne, Parkville, Victoria, Australia Urology Department, Royal Children’s Hospital, Parkville, Victoria, Australia More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2014.10.024AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: Undescended testis leads to infertility and malignancy resulting from aberrant germ cell development. Androgens are proposed to control early germ cell development during the transient postnatal surge of gonadotropins and androgen, known as mini-puberty. We assessed the effect of androgen receptor on perinatal germ cell development in mice. Materials and Methods: Testes from androgen receptor knockout mice and wild-type littermates (3 to 4 per group) were collected at embryonic day 17 and postnatal days 0 (birth), 2, 4, 6, 8 and 10 for immunohistochemical analysis. Antibodies against mouse VASA homologue (germ cell marker), antimüllerian hormone (Sertoli cell marker), Ki67 (proliferating cell marker) and DAPI (nuclei) were used and visualized by confocal microscopy. Number of germ cells per tubule, germ cells on the tubular basement membrane and Sertoli cells per tubule, and percentage of proliferating germ cells (Ki67+) per tubule and germ cells (Ki67+) on the basement membrane on confocal images were counted using Image J, version 1.44 (http://imagej.nih.gov/ij/). Data were analyzed using nonparametric one-way ANOVA with GraphPad Prism® 5.02 software. Results: In wild-type and androgen receptor knockout testes germ cells per tubule decreased from embryonic day 17 to postnatal day 2, then increased normally. Number of mouse VASA homologue positive germ cells per tubule and germ cells on the basement membrane were similar in androgen receptor knockout and wild-type testes (p >0.05) at each age, and percentages of proliferating germ cells (Ki67+) per tubule and proliferating germ cells on the basement membrane were similar at each age (p >0.05). Conclusions: Androgen receptors are not required for gonocyte migration from the center of the testicular tubules to the basement membrane and transformation into spermatogonia stem cells up to day 10 in androgen receptor knockout mice. Identifying nonandrogenic factors might improve the fertility potential of boys with undescended testis who are undergoing orchiopexy. References 1 : Germ cell development in the postnatal testis: the key to prevent malignancy in cryptorchidism?. Front Endocrinol (Lausanne)2013; 3: 176. Google Scholar 2 : The pituitary-gonadal axis in cryptorchid infants and children. Eur J Pediatr1987; 146: S2. Google Scholar 3 : Human spermatogonial stem cells: a possible origin for spermatocytic seminoma. Int J Androl2011; 34: e296. Google Scholar 4 : Renewal of spermatogonia in man. Am J Anat1966; 118: 509. Google Scholar 5 : A critical appraisal of the evidence for improved fertility indices in undescended testes after gonadotrophin-releasing hormone therapy and orchidopexy. J Pediatr Urol2010; 6: 239. Google Scholar 6 : The importance of both an early orchidopexy and germ cell maturation for fertility. Lancet2001; 358: 1156. Google Scholar 7 : Regulation of Sertoli cell number and activity by follicle-stimulating hormone and androgen during postnatal development in the mouse. Endocrinology2004; 145: 318. Google Scholar 8 : The role of androgens in Sertoli cell proliferation and functional maturation: studies in mice with total or Sertoli cell-selective ablation of the androgen receptor. Endocrinology2005; 146: 2674. Google Scholar 9 : Testicular development in mice lacking receptors for follicle stimulating hormone and androgen. PLoS One2012; 7: e35136. Google Scholar 10 : Differential effects of spermatogenesis and fertility in mice lacking androgen receptor in individual testis cells. Proc Natl Acad Sci U S A2006; 103: 18975. Google Scholar 11 : Testicular development in the complete androgen insensitivity syndrome. J Pathol2006; 208: 518. Google Scholar 12 : Morphological and immunohistochemical differences between gonadal maturation delay and early germ cell neoplasia in patients with undervirilization syndromes. J Clin Endocrinol Metab2005; 90: 5295. Google Scholar 13 : Genomic actions of the androgen receptor are required for normal male sexual differentiation in a mouse model. J Mol Endocrinol2005; 35: 547. Google Scholar 14 : Spermatogonial morphology and kinetics during testis development in mice: a high-resolution light microscopy approach. Reproduction2011; 142: 145. Google Scholar 15 : Immunofluorescent analysis of testicular biopsies with germ cell and Sertoli cell markers shows significant MVH negative germ cell depletion with older age at orchiopexy. J Urol2014; 191: 458. Link, Google Scholar 16 : Mullerian inhibiting substance: a gonadal hormone with multiple functions. Endocr Rev1993; 14: 152. Google Scholar 17 : Spermatogenesis and Sertoli cell activity in mice lacking Sertoli cell receptors for follicle-stimulating hormone and androgen. Endocrinology2008; 149: 3279. Google Scholar 18 : Reinitiation of gonocyte mitosis and movement of gonocytes to the basement membrane in testes of newborn rats in vivo and in vitro. Anat Rec1992; 233: 527. Google Scholar 19 : Gonocyte transformation to spermatogonial stem cells occurs earlier in patients with undervirilisation syndromes. J Pediatr Surg2014; 49: 323. Google Scholar 20 : Gonadal differentiation—normal and abnormal testicular development. Adv Exp Med Biol2002; 511: 15. Google Scholar 21 : The role of follicle-stimulating hormone in spermatogenesis: lessons from knockout animal models. Arch Med Res2001; 32: 601. Google Scholar 22 : Regulation of germ cell and Sertoli cell development by activin, follistatin, and FSH. Dev Biol2000; 220: 225. Google Scholar 23 : Serum inhibin B as a marker of spermatogenesis. J Clin Endocrinol Metab1998; 83: 3110. Google Scholar 24 : Serum levels of Mullerian inhibiting substance in boys with cryptorchidism. J Pediatr Surg1991; 26: 621. Google Scholar 25 : Germ cell development in neonatal mouse testes in vitro requires müllerian inhibiting substance. J Urol1993; 150: 613. 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Google Scholar © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetailsCited byAtala A (2018) Re: PrESOgenesis: A Two-Layer Multi-Label Predictor for Identifying Fertility-Related Proteins Using Support Vector Machine and Pseudo Amino Acid Composition ApproachJournal of Urology, VOL. 201, NO. 1, (34-34), Online publication date: 1-Jan-2019.Atala A (2018) Re: AgRP to Kiss1 Neuron Signaling Links Nutritional State and FertilityJournal of Urology, VOL. 200, NO. 3, (501-501), Online publication date: 1-Sep-2018.Atala A (2016) Re: Genome Engineering Uncovers 54 Evolutionarily Conserved and Testis-Enriched Genes That are Not Required for Male Fertility in MiceJournal of Urology, VOL. 196, NO. 6, (1817-1817), Online publication date: 1-Dec-2016.Ritchey M (2015) This Month in Pediatric UrologyJournal of Urology, VOL. 193, NO. 4, (1079-1080), Online publication date: 1-Apr-2015. Volume 193Issue 4April 2015Page: 1361-1367 Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.Keywordstestisandrogenscryptorchidismgerm cellsspermatogoniaAcknowledgmentsProf. J. Zajac, Austin Hospital, Melbourne, supplied the founder animals.MetricsAuthor Information Ruili Li Douglas Stephens Surgical Research Laboratory, Murdoch Children’s Research Institute, Parkville, Victoria, Australia Department of Pediatrics, University of Melbourne, Parkville, Victoria, Australia More articles by this author Amanda Vannitamby Douglas Stephens Surgical Research Laboratory, Murdoch Children’s Research Institute, Parkville, Victoria, Australia More articles by this author Jorien Meijer Medical School, University of Groningen, Groningen, The Netherlands More articles by this author Bridget Southwell Douglas Stephens Surgical Research Laboratory, Murdoch Children’s Research Institute, Parkville, Victoria, Australia Department of Pediatrics, University of Melbourne, Parkville, Victoria, Australia More articles by this author John Hutson Douglas Stephens Surgical Research Laboratory, Murdoch Children’s Research Institute, Parkville, Victoria, Australia Department of Pediatrics, University of Melbourne, Parkville, Victoria, Australia Urology Department, Royal Children’s Hospital, Parkville, Victoria, Australia More articles by this author Expand All Advertisement PDF downloadLoading ...
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