Differential Impact of Subcutaneous Neurokinin B Administration on Epididymal Proliferation in Adult New Zealand White Rabbits: A Dose-Dependent Study
DOI:
https://doi.org/10.51253/pafmj.v74i1.11435Keywords:
Epididymis, Histomorphology, Neurokinin B, Spermatozoa, TachykininsAbstract
Objective: To investigate the potential of variable doses of Neurokinin B on histomorphology of epididymis in adult rabbits.
Study Design: Laboratory-based experimental study.
Place and Duration of Study: Gomal Centre of Biochemistry and Biotechnology, Gomal University, Dera Ismail Khan, Pakistan, from Jun 2019 to Jun 2020.
Methodology: Adult male New Zealand White rabbits with an average weight of 1.5–2 Kg were randomly assigned to three groups. Study animals were administered subcutaneously with Neurokinin B in two variable doses: 1 µg and one ηg. Control rabbits were injected with distilled water in parallel. After 12 days of continuous peptide treatment, animals (n=06) in each group were sacrificed. Epididymis were dissected and processed for light microscopy and sperm count.
Results: Mean epididymis weight (mg) increased significantly (p<0.001) with the treatment of Neurokinin B 1 ηg and Neurokinin B 1 µg as compared to control. With the increase in doses of Neurokinin B (1 ηg, 1 μg), the lumen of caput, corpus and cauda of the epididymis got significantly (p<0.001) dilated dose-dependently in Neurokinin B treated animals. Sperm count increased significantly (p<0.001) in the Neurokinin B-treated rabbits compared to the control. Light microscopy revealed increased luminal diameter compared to control in all Neurokinin B treated groups as compared to control.
Conclusion: Continuous administration of Neurokinin B could benefit the epididymis, as shown by increased luminal diameter and sperm count.
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References
Sherwood L. Human Physiology: From Cells to Systems. Ninth ed. Boston, MA 02210, USA: Cengage Learning; 2016.
Almeida TA, Rojo J, Nieto PM, Pinto FM, Hernandez M, Martín JD, et al. Tachykinins and tachykinin receptors: structure and activity relationships. Curr Med Chem 2004; 11(15): 2045-2081.
https://doi.org/10.2174/0929867043364748.
Page NM, Woods RJ, Gardiner SM, Lomthaisong K, Gladwell RT, Butlin DJ, et al. Excessive placental secretion of neurokinin B during the third trimester causes pre-eclampsia. Nature 2000; 405(6788): 797-800. https://doi.org/10.1038/35015579.
Topaloglu AK, Reimann F, Guclu M, Yalin AS, Kotan LD, Porter KM, et al. TAC3 and TACR3 mutations in familial hypogonadotropic hypogonadism reveal a key role for Neurokinin B in the central control of reproduction. Nat Genet 2009; 41(3): 354-358. https://doi.org/10.1038/ng.306.
Young J, Bouligand J, Francou B, Raffin-Sanson ML, Gaillez S, Jeanpierre M, et al. TAC3 and TACR3 defects cause hypothalamic congenital hypogonadotropic hypogonadism in humans. J Clin Endocrinol Metab 2010; 95(5): 2287-2295.
https://doi.org/10.1210/jc.2009-2600.
Corander MP, Challis BG, Thompson EL, Jovanovic Z, Loraine Tung YC, Rimmington D, et al. The effects of neurokinin B upon gonadotrophin release in male rodents. J Neuroendocrinol 2010;22(3): 181-187.
https://doi.org/10.1111/j.1365-2826.2009.01951.x.
Ruiz-Pino F, Garcia-Galiano D, Manfredi-Lozano M, Leon S, Sánchez-Garrido MA, Roa J, et al. Effects and interactions of tachykinins and dynorphin on FSH and LH secretion in developing and adult rats. Endocrinology 2015; 156(2): 576-588.
https://doi.org/10.1210/en.2014-1026.
Navarro VM, Bosch MA, León S, Simavli S, True C, Pinilla L, et al. The integrated hypothalamic tachykinin-kisspeptin system as a central coordinator for reproduction. Endocrinology 2015; 156(2): 627-637. https://doi.org/10.1210/en.2014-1651.
Skorupskaite K, George J, Anderson RA. Role of a neurokinin B receptor antagonist in the regulation of ovarian function in healthy women. Lancet 2015; 385 (Suppl 1): S92.
https://doi.org/10.1016/s0140-6736(15)60407-x.
European Animal Research Association. EU regulations on animal research London, England: European Animal Research Association. Available at: https://www.eara.eu/animal-research-law [Accessed on November 28, 2023].
Szeliga A, Podfigurna A, Bala G, Meczekalski B. Kisspeptin and neurokinin B analogs use in gynecological endocrinology: where do we stand? J Endocrinol Invest 2020; 43(5): 555-561.
https://doi.org/10.1007/s40618-019-01160-0.
Thompson EL, Murphy KG, Patterson M, Bewick GA, Stamp GW, Curtis AE, et al. Chronic subcutaneous administration of kisspeptin-54 causes testicular degeneration in adult male rats. Am J Physiol Endocrinol Metab 2006; 291(5): E1074-1082.
https://doi.org/10.1152/ajpendo.00040.2006.
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.
https://doi.org/10.1016/j.lfs.2010.11.019.
True C, Nasrin Alam S, Cox K, Chan Y-M, Seminara SB. Neurokinin B Is Critical for Normal Timing of Sexual Maturation but Dispensable for Adult Reproductive Function in Female Mice. Endocrinology 2015; 156(4): 1386-1397.
https://doi.org/10.1210/en.2014-1862.
Garcia JP, Keen KL, Kenealy BP, Seminara SB, Terasawa E. Role of Kisspeptin and Neurokinin B Signaling in Male Rhesus Monkey Puberty. Endocrinology 2018; 159(8): 3048-3060.
https://doi.org/10.1210/en.2018-00443.
Rea M, Marshall G, Weinbauer G, Nieschlag E. Testosterone maintains pituitary and serum FSH and spermatogenesis in gonadotrophin-releasing hormone antagonist-suppressed rats. J Endocrinol 1986; 108(1): 101-107.
Hamzeh M, Robaire B. Effect of testosterone on epithelial cell proliferation in the regressed rat epididymis. J Androl 2009; 30(2): 200-212.
Mclachlan RI, Wreford NG, Meachem SJ, De Kretser DM, Robertson DM. Effects of Testosterone on Spermatogenic Cell Populations in the Adult Rat. Biol Reprod 1994; 51(5): 945-955.
https://doi.org/10.1095/biolreprod51.5.945.
Candenas L, Lecci A, Pinto FM, Patak E, Maggi CA, Pennefather JN. Tachykinins and tachykinin receptors: effects in the genitourinary tract. Life Sci 2005; 76(8): 835-862.
https://doi.org/10.1016/j.lfs.2004.10.004.
van Kroonenburgh MJPG, Beck JL, Vemer HM, Rolland R, Thomas CMG, Herman CJ, et al. Effects of a single injection of a new depot formulation of an LH-releasing hormone agonist on spermatogenesis in adult rats. J Endocrinol 1986; 111(3): 449-NP.
https://doi.org/10.1677/joe.0.1110449.
Hsueh AJW, Schaeffer JM. Gonadotropin-releasing hormone as a paracrine hormone and neurotransmitter in extra-pituitary sites. J Steroid Biochem 1985; 23(5, Part 2): 757-764.
https://doi.org/10.1016/S0022-4731(85)80011-X.
Sasaki T, Sonoda T, Tatebayashi R, Kitagawa Y, Oishi S, Yamamoto K, et al. Peripheral administration of SB223412, a selective neurokinin-3 receptor antagonist, suppresses pulsatile luteinizing hormone secretion by acting on the gonadotropin-releasing hormone pulse generator in estrogen-treated ovariectomized female goats. J Reprod Develop 2020; 66(4): 351-357. https://doi.org/10.1262/jrd.2019-145.
Ramaswamy S, Seminara SB, Ali B, Ciofi P, Amin NA, Plant TM, et al. Neurokinin B stimulates GnRH release in the male monkey (Macaca mulatta) and is colocalized with kisspeptin in the arcuate nucleus. Endocrinology 2010; 151(9): 4494-4503.
https://doi.org/10.1210/en.2010-0223.
Johnson LC, Fisher G, Silvester JL, Hofheins CC. Anabolic steroid: effects on strength, body weight, oxygen uptake and spermatogenesis upon mature males. Med Sci Sports Exerc 1972; 4(1): 43-46.
Zirkin BR. Spermatogenesis: its regulation by testosterone and FSH. Semin Cell Dev Biol 1998; 9(4): 417-421.