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Reproductive Biology and Endocrinology
Published in: Reproductive Biology and Endocrinology 1/2012

Open Access 01-12-2012 | Research

Immature rat seminal vesicles show histomorphological and ultrastructural alterations following treatment with kisspeptin-10

Authors: Faiqah Ramzan, Irfan Zia Qureshi, Muhammad Ramzan, Muhammad Haris Ramzan, Faiza Ramzan

Published in: Reproductive Biology and Endocrinology | Issue 1/2012

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Abstract

Background

Degenerative effects of critical regulators of reproduction, the kisspeptin peptides, on cellular aspects of sexually immature male gonads are known but similar information on accessory sex glands remain elusive.

Methods

Prepubertal laboratory rats were injected kisspeptin-10 at three different dosage concentrations (10 pg, 1 ng and 1 microgram) for a period of continuous 12 days at the rate of two doses per day. Control rats were maintained in parallel. The day following the end of the experimental period, seminal vesicles were removed and processed for light and electron microscopic examination using the standard methods. DNA damage was estimated by DNA ladder assay and DNA fragmentation assay.

Results

The results demonstrated cellular degeneration. Epithelial cell height of seminal vesicles decreased significantly at all doses (P < 0.05). Marked decrease in epithelial folds was readily noticeable, while the lumen was dilated. Ultrastructural changes were characterized by dilatation of endoplasmic reticulum and Golgi complex, heterochromatization of nuclei, invagination of nuclear membranes and a decreased number of secretory granules. Percent DNA damage to the seminal vesicle was 19.54 +/- 1.98, 38.06 +/- 2.09 and 58.18 +/- 2.59 at 10 pg, 1 ng and 1 microgram doses respectively.

Conclusion

The study reveals that continuous administration of kisspeptin does not lead to an early maturation but instead severe degeneration of sexually immature seminal vesicles.
Appendix
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Literature
1.
Lee JH, Miele ME, Hicks DJ, Phillips KK, Trent JM, Weissman BE, Welch DR: KiSS-1, a novel human malignant melanoma metastasis-suppressor gene. J Natl Cancer Inst. 1996, 88: 1731-1737. 10.1093/jnci/88.23.1731.CrossRefPubMed
2.
Kotani M, Detheux M, Vandenbogaerde A, Communi D, Vanderwinden JM, Le Poul E, Brezillon S, Tyldesley R, Suarez-Huerta N, Vandeput F, Blanpain C, Schiffmann S, Vassart G, Parmentier M: The metastasis suppressor gene KiSS-1 encodes kisspeptins, the natural ligands of the orphan G protein-coupled receptor GPR54. J Biol Chem. 2001, 276: 34631-34636. 10.1074/jbc.M104847200.CrossRefPubMed
3.
Ohtaki T, Shintani Y, Honda S, Matsumoto H, Hori A, Kanehashi K, Terao Y, Kumano S, Takatsu Y, Masuda Y, Ishibashi Y, Watanabe T, Asada M, Yamada T, Suenaga M, Kitada C, Usuki S, Kurokawa T, Onada H, Nishimura O, Fujino M: Metastasis suppressor gene KiSS-1 encodes peptide ligand of a G-protein-coupled receptor. Nature. 2001, 411: 613-617. 10.1038/35079135.CrossRefPubMed
4.
Stafford LJ, MaW Xia, Cai Y, Liu M: Identification and characterization of mouse metastasis-suppressor KiSS1 and its G-protein-coupled receptor. Cancer Res. 2002, 62: 5399-5404.PubMed
5.
de Roux N, Genin E, Carel JC, Matsuda F, Chaussain JL, Milgrom E: Hypogonadotropic hypogonadism due to loss of function of the KiSS1-derived peptide receptor GPR54. Proc Natl Acad Sci USA. 2003, 100: 10972-10976. 10.1073/pnas.1834399100.PubMedCentralCrossRefPubMed
6.
Seminara SB, Messager S, Chatzidaki EE, Thresher RR, Acierno JS, Shagoury JK, Bo-Abbas Y, Kuohung W, Schwinof KM, Hendrick AG, Zahn D, Dixon J, Kaiser UB, Slaugenhaupt SA, Gusella JF, O'Rahilly S, Carlton MB, Crowley WF, Aparicio SA, Colledge WH: The GPR54 gene as a regulator of puberty. N Engl J Med. 2003, 349: 1614-1627. 10.1056/NEJMoa035322.CrossRefPubMed
7.
Gottsch ML, Cunningham MJ, Smith JT, Popa SM, Acohido BV, Crowley WF, Seminara S, Clifton DK, Steiner RA: A role for kisspeptins in the regulation of gonadotropin secretion in the mouse. Endocrinology. 2004, 145: 4073-4077. 10.1210/en.2004-0431.CrossRefPubMed
8.
Smith JT, Cunningham MJ, Rissman EF, Clifton DK, Steiner RA: Regulation of Kiss1 gene expression in the brain of the female mouse. Endocrinology. 2005, 146: 3686-3692. 10.1210/en.2005-0488.CrossRefPubMed
9.
Smith JT, Dungan HM, Stoll EA, Gottsch ML, Braun RE, Eacker SM, Clifton DK, Steiner RA: Differential regulation of KiSS-1 mRNA gene expression by sex steroids in the brain of the male mouse. Endocrinology. 2005, 146: 2976-2984. 10.1210/en.2005-0323.CrossRefPubMed
10.
Navarro VM, Castellano JM, Fernandez-Fernandez R, Barreiro ML, Roa J, Sanchez-Criado JE, Aguilar E, Dieguez C, Pinilla L, Tena-Sempere M: Developmental and hormonally regulated messenger ribonucleic acid expression of KiSS-1 and its putative, receptor, GPR54, in rat hypothalamus and potent luteinizing hormone-releasing activity of KiSS-1 peptide. Endocrinology. 2004, 145: 4565-4574. 10.1210/en.2004-0413.CrossRefPubMed
11.
Irwig MS, Fraley GS, Smith JT, Acohido BV, Popa SM, Cunningham MJ, Gottsch ML, Clifton DK, Steiner RA: Kisspeptin activation of gonadotropin releasing hormone neurons and regulation of KiSS-1 mRNA in the male rat. Neuroendocrinology. 2004, 80: 264-272. 10.1159/000083140.CrossRefPubMed
12.
Navarro VM, Fernandez-Fernandez R, Castellano JM, Roa J, Mayen A, Barreiro ML, Gaytan F, Aguilar E, Pinilla L, Dieguez C, Tena-Sempere M: Advanced vaginal opening and precocious activation of the reproductive axis by KiSS-1, peptide, the endogenous ligand of GPR54. J Physiol. 2004, 561: 379-386. 10.1113/jphysiol.2004.072298.PubMedCentralCrossRefPubMed
13.
Shahab M, Mastronardi C, Seminara SB, Crowley WF, Ojeda SR, Plant TM: Increased hypothalamic GPR54 signaling: a potential mechanism for initiation of puberty in primates. Proc Natl Acad Sci USA. 2005, 102: 2129-2134. 10.1073/pnas.0409822102.PubMedCentralCrossRefPubMed
14.
Smith JT, Rao A, Pereira A, Caraty A, Millar RP, Clarke IJ: Kisspeptin is present in ovine hypophysial portal blood but does not increase during the preovulatory luteinizing hormone surge: evidence that gonadotropes are not direct targets of kisspeptin in vivo. Endocrinology. 2008, 149: 1951-1959. 10.1210/en.2007-1425.CrossRefPubMed
15.
Richard N, Corvaisier S, Camacho E, Kottler ML: KiSS-1 and GPR54 at the pituitary level: overview and recent insights. Peptides. 2009, 30: 123-129. 10.1016/j.peptides.2008.09.015.CrossRefPubMed
16.
Belchetz PE, Plant TM, Nakai Y, Keogh EJ, Knobil E: Hypophysial responses to continuous and intermittent delivery of hypothalamic gonadotropin-releasing hormone. Science. 1978, 202: 631-633. 10.1126/science.100883.CrossRefPubMed
17.
McArdle CA, Gorospe WC, Huckle WR, Conn PM: Homologous down-regulation of gonadotropin-releasing hormonereceptorsanddesensitization of gonadotropes: lack of dependence on protein kinase C. Mol Endocrinol. 1987, 1: 420-429. 10.1210/mend-1-6-420.CrossRefPubMed
18.
Wu JC, Sealfon SC, Miller WL: Gonadal hormones and gonadotropin-releasing hormone (GnRH) alter messenger ribonucleic acid levels for GnRH receptors in sheep. Endocrinology. 1994, 134: 1846-1850. 10.1210/en.134.4.1846.PubMed
19.
Vizcarra JA, Wettemann RP, Braden TD, Turzillo AM, Nett TM: Effect of gonadotropin-releasing hormone (GnRH) pulse frequency on serum and pituitary concentrations of luteinizing hormone and follicle-stimulating, hormone, GnRH, receptors, and messenger ribonucleic acid for gonadotropin subunits in cows. Endocrinology. 1997, 138: 594-601. 10.1210/en.138.2.594.PubMed
20.
Mason DR, Arora KK, Mertz LM, Catt KJ: Homologous down-regulation of gonadotropin-releasing hormone receptor sites and messenger ribonucleic acid transcripts in a T-31 cells. Endocrinology. 1994, 135: 1165-1170. 10.1210/en.135.3.1165.PubMed
21.
Seminara SB, Dipietro MJ, Ramaswamy S, Crowley WF, Plant TM: Continuous human metastin 45-54 infusion desensitizes G protein-coupled receptor 54-induced gonadotropin-releasing hormone release monitored indirectly in the juvenile male Rhesus monkey (Macaca mulatta): a finding with therapeutic implications. Endocrinology. 2006, 147: 2122-2126. 10.1210/en.2005-1550.CrossRefPubMed
22.
Ramaswamy S, Seminara SB, Pohl CR, DiPietro MJ, Crowley WF, Plant TM: Effect of continuous intravenous administration of human metastin 45-54 on the neuroendocrine activity of the hypothalamic-pituitary-testicular axis in the adult male rhesus monkey (Macaca mulatta). Endocrinology. 2007, 148: 3364-3370. 10.1210/en.2007-0207.CrossRefPubMed
23.
Thompson EL, Murphy KG, Patterson M, Bewick GA, Stamp GWH, Curtis AE, Cooke JH, Jethwa PH, Todd JF, Ghatei MA, Bloom SR: Chronic subcutaneous administration of kisspeptin-54 causes testicular degeneration in adult male rats. Am J Physiol Endocrinol Metab. 2006, 291: 1074-1082. 10.1152/ajpendo.00040.2006.CrossRef
24.
Tovar S, Vázquez MJ, Navarro VM, Fernández-Fernández R, Vigo E, Rao J, Casanueva FF, Anguilar E, Pinilla L, Dieguez C, Tena-Sempere M: Effects of single or repeated intravenous administration of kisspeptin upon dynamic LH secretion in conscious male rats. Endocrinology. 2006, 147: 2696-2704. 10.1210/en.2005-1397.CrossRefPubMed
25.
Plant TM, Ramaswamy S, Dipietro MJ: Repetitive activation of hypothalamic G-protein coupled receptor 54 with intravenous pulses of kisspeptin in the juvenilemonkey(Macaca mulatta) elicits a sustained train of gonadotropin-releasing hormone discharges. Endocrinology. 2006, 147: 1007-1013.CrossRefPubMed
26.
Higgins SJ, Burchell JM, Mainwaring WIP: Testosterone control of nucleic acid content and proliferation of epithelium and stroma in rat seminal vesicles. Biochem J. 1976, 160: 43-74.PubMedCentralCrossRefPubMed
27.
Bloom W, Fawcett DW: Male reproductive system. A textbook of histology. 1976, Philadelphia, London, Toronto: W. B. Saunders Company, 805-855. 10
28.
Tao YX, Lei ZM, Rao CV: Seminal vesicles are novel sites of luteinizing hormone/human chorionic gonadotropin receptor gene expression. J Androl. 1998, 19: 343-347.PubMed
29.
Higgins SJ, Burchell JM: Effects of testosterone on messenger ribonucleic acid and protein synthesis in rat seminal vesicle. Biochem J. 1978, 174: 543-551.PubMedCentralCrossRefPubMed
30.
Lieber MM, Barham SS, Veneziale CM: In vitro propagation of seminal vesicle epithelial cells. Invest Urol. 1980, 17: 348-PubMed
31.
Dhillo WS, Chaudhri OB, Patterson M, Thompson EL, Murphy KG, Badman MK, McGowan BM, Amber V, Patel S, Ghatei MA, Bloom SR: Kisspeptin-54 stimulates the hypothalamic-pituitary gonadal axis in human males. J Clin Endocrinol Metab. 2005, 90: 6609-6615. 10.1210/jc.2005-1468.CrossRefPubMed
32.
Gilbert MTP, Haselkorn T, Bunce M, Sanchez JJ, Lucas SB, Jewell LD, van Marck E, Worobey M: The isolation of nucleic acids from fixed, paraffin-embedded tissues - which methods are useful when?. PLoS ONE 2. 2007, 6: e537-doi:10.1371/journal.pone.0000537CrossRef
33.
Boraschi D, Maurizi G: Quantitation of DNA fragmentation with diphenylamine. Apoptosis - A Laboratory Manual of Experimental Methods. Edited by: Boraschi D, Bossù P, Cossarizza A. 1998, L'Aquila: GCI Publications, 153-161.
34.
Roa J, Navarro VM: Tena-Sempere M. Kisspeptins in reproductive biology: consensus knowledge and recent developments. Biol Reprod. 2011, 85 (4): 650-660. 10.1095/biolreprod.111.091538.CrossRefPubMed
35.
Ramzan F, Qureshi IZ: Intraperitoneal kisspeptin-10 administration induces dose-dependent degenerative changes in maturing rat testes. Life Sci. 2011, 88 (5-6): 246-256. 10.1016/j.lfs.2010.11.019.CrossRefPubMed
36.
Thompson EL, Amber V, Stamp GW, Patterson M, Curtis AE, Cooke JH, Appleby GF, Dhillo WS, Ghatei MA, Bloom SR, Murphy KG: Kisspeptin-54 at high doses acutely induces testicular degeneration in adult male rats via central mechanisms. Br J Pharmacol. 2009, 156: 609-625. 10.1111/j.1476-5381.2008.00061.x.PubMedCentralCrossRefPubMed
37.
Fawcett DW, Bloom W, Fawcett DW: A textbook of histology. 1986, Philadelphia: W.B. Saunders, 796-850.
38.
Brandes D: Male Accessory Sex Organs: structure and function in mammals. 1974, New York: Academic Press, 527-
39.
Veneziale CM, Steer RC, Buchi KA: Guinea pig seminal vesicle epithelium: a model for androgen action in Regulatory Mechanisms Affecting Gonadal Hormone Action. 1977, Baltimore: University Park Press, 103-168.
40.
Veneziale CM, Bums JM, Lewis JC, Buchi KA: Specific protein synthesis in isolated epithelium of guinea pig seminal vesicle: effects of castration and androgen replacement. Biochem J. 1977, 166: 167-173.PubMedCentralCrossRefPubMed
41.
Aumuller G, Giers K, Giers U, Volk A, Seitz J: p-Chlorophennylalanine-induced proliferation of the seminal vesicle epithelium. Cell Tissue Res. 1981, 219: 159-172.CrossRefPubMed
42.
Roa J, Vigo E, Garcia-Galiano D, Castellano JM, Navarro VM, Pineda R, Dieguez C, Aguilar E, Pinilla L, Tena-Sempere M: Desensitization of gonadotropin responses to kisspeptin in the female rat: analyses of LH and FSH secretion at different developmental and metabolic states. Am J Physiol Endocrinol Metab. 2008, 294: E1088-1096. 10.1152/ajpendo.90240.2008.CrossRefPubMed
43.
Redmond JS, Macedo GG, Velez IC, Caraty A, Williams GL, Amstalden M: Kisspeptin activates the hypothalamic-adenohypophyseal-gonadal axis in prepubertal ewe lambs. Reproduction. 2011, 141: 541-548. 10.1530/REP-10-0467.CrossRefPubMed
44.
Rhie YJ, Lee KH, Eun SH, Choi BM, Chae HW, Kwon AR, Lee WJ, Kim JH, Kim HS: Serumkisspeptin levels in Korean girls with central precocious puberty. J Korean Med Sci. 2011, 26 (7): 927-931. 10.3346/jkms.2011.26.7.927.PubMedCentralCrossRefPubMed
Metadata
Title
Immature rat seminal vesicles show histomorphological and ultrastructural alterations following treatment with kisspeptin-10
Authors
Faiqah Ramzan
Irfan Zia Qureshi
Muhammad Ramzan
Muhammad Haris Ramzan
Faiza Ramzan
Publication date
01-12-2012
Publisher
BioMed Central
Published in
Reproductive Biology and Endocrinology / Issue 1/2012
Electronic ISSN: 1477-7827
DOI
https://doi.org/10.1186/1477-7827-10-18

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