The online version of this article (doi:10.1186/1477-7827-10-18) contains supplementary material, which is available to authorized users.
The authors declare that they have no competing interests.
FR has conducted the entire work, designed the study and drafted the manuscript. IZQ has supervised the study. MR and MHR has contributed the data analysis. FR has contributed to histology. All authors read and authorized the final manuscript.
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.
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.
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.
The study reveals that continuous administration of kisspeptin does not lead to an early maturation but instead severe degeneration of sexually immature seminal vesicles.
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
Bloom W, Fawcett DW: Male reproductive system. A textbook of histology. 1976, Philadelphia, London, Toronto: W. B. Saunders Company, 805-855. 10
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
Lieber MM, Barham SS, Veneziale CM: In vitro propagation of seminal vesicle epithelial cells. Invest Urol. 1980, 17: 348- PubMed
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.0000537 CrossRef
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.
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
Fawcett DW, Bloom W, Fawcett DW: A textbook of histology. 1986, Philadelphia: W.B. Saunders, 796-850.
Brandes D: Male Accessory Sex Organs: structure and function in mammals. 1974, New York: Academic Press, 527-
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.
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
- Immature rat seminal vesicles show histomorphological and ultrastructural alterations following treatment with kisspeptin-10
Irfan Zia Qureshi
Muhammad Haris Ramzan
- BioMed Central
Neu im Fachgebiet Gynäkologie und Geburtshilfe
Meistgelesene Bücher aus dem Fachgebiet
e.Med Kampagnen-Visual, Mail Icon II