Disclosure Efficacy of Chronic Administration of Leptin Supplement on Spermatogenesis in Male Rats

Authors

  • Ahmed Salman Abdulhasan Department of Biology, College of Science, University of Thi - Qar
  • Samara Yahya Kraidi Department of Pharmacology, College of Pharmacy, Al-Muthanna University
  • Nuha jabori Hadi Department of Biology, College of Science, University of Thi – Qar

Keywords:

Leptin, Spermatogenesis Status, Mal Rat, LH, FSH

Abstract

This study is undertaken the explore effect of chronic leptin administration on body weight, reproductive organ weight, sperm count and male sex hormones. Rats were treated daily with a single intraperitoneal injection   15g/kg body weight of leptin for 45 days. Body weight, were measured every five days over the experimental periods.  At the end of treatment, rats were anesthetized with ether and immediately killed by cervical dislocation. The right epididymis was removed and minced in 2 ml normal saline. The suspension was filtered and stained with 1 % eosin. Sperm count were conducted.  Blood was collected from the heart puncture, clotted and centrifuged to obtain the serum. Serum testosterone, FSH, LH and leptin were measured using ELISA technique. The testis, epididymis and prostate were calculated their relative organ weights. In this study was significantly decrease body weight in leptin-treated group. However, Serum testosterone, FSH and LH levels were however increased significantly in leptin-treated group compared to controls. Sperm count was significant lower in leptin-treated groups when compared to age-matched controls. Conclusion  It appeared leptin administration in daily doses for long term, significantly affecting body; seem to significantly increase weight, levels serum for testosterone FSH and LH levels in male rats.  In addition, it also decreases sperm counts. Subsequently, leptin exposure is causing impairment of spermatogenesis.

References

Dearth, R. K., Hiney, J. K. & Dees, W. L. (2000). Leptin acts centrally to induce the prepubertal secretion of luteinizing hormone in the female rat. Peptides, 21(3), 38792.

Franca LR., Suescun MO, Miranda JR, Giovambattista, Perello M, Spinedi E, Calandra RS. (2006) Testis structure and function in a non-genetic hyperadipose rat model at prepubertal and adult ages. Endocrinology 147(3):1556-1563.

Friedman, J., Leibel, R. L., Siegel, D. A., Walsh, J. & Bahary, N. (1991). Molecular mapping of the mouse ob mutation. Genomics, 111054-1062

Ghosh, D., Das Sarkar, S., Maiti, R., Jana, D. & Das, U. B. (2002). Testicular toxicity in sodium fluoride treated rats: association with oxidative stress. Reprod Toxicol, 16(4), 385-90.

Gonzalez, L. C., Pinilla, L., Tena-Sempere, M. & Aguilar, E. (1999). Leptin(116-130) stimulates prolactin and luteinizing hormone secretion in fasted adult male rats. Neuroendocrinology, 70(3), 2120.

Hamilton, B. S., Paglia, D., Kwan, A. Y. & Deitel, M. (1995). Increased obese mRNA expression in omental fat cells from massively obese humans. Nat Med, 1(9), 953-6.

Hanafy S., Halawa FA., Mostafa T., Mikhael NW., Khalil KT. (2007) Serum leptin correlates in infertile oligozoospermic males. Andrologica 39:177-180

Henry B, Goding J, Tilbrook A, Dunshea FR, Clarke IJ (2001). Intracerebroventricular infusion of leptin elevates the secretion of luteinising hormone without affecting food intake in long-term food restricted sheep, but increases growth hormone irrespective of body weight. J Endocrinol. 168:677

Heymsfield SB, Greenberg AS, Fujioka K, Dixon RM, Kushner R, Hunt T, lubina JA, Patane J, Self B, Hunt P, Mccamish M. (1999). Recombinant leptin for weight loss in obese and lean adults: a randomised, controlled, dose-escalation trial. JAMA;282:1568-1575.

Houseknecht, K. L. & Portocarrero, C. P. (1998). Leptin and its receptors: regulators of whole-body energy homeostasis. Domest Anim Endocrinol, 15(6), 457-75.

Houseknecht, K. L., Flier, S. N., Frevert, E. U., Frederich, R. C., Flier, J. S. & Kahn, B. B. (1996). Leptin secretion correlates with adipocytes size in genetic and dietary obesity. Diabetes, 4541.

Hube, F., Lietz, U., Igel, M., Jensen, P. B., Tornqvist, H., Joost, H. G. & Hauner, H. (1996). Difference in leptin mRNA levels between omental and subcutaneous abdominal adipose tissue from obese humans. Horm Metab Res, 28(12), 690-3

Isidori, A. M., Strollo, F., More, M., Caprio, M., Aversa, A., Moretti, C., Frajese, G., Riondino, G. & Fabbri, A. (2000). Leptin and aging: correlation with endocrine changes in male and female healthy adult populations of different body weights. J Clin Endocrinol Metab, 85(5), 1954-62.

Jin L, Burguera BG, Couce ME, Scheithauer BW, Lamsan J, Eberhardt NL, Kulig E, Lloyd RV (1999) Leptin and leptin receptor expression in normal and neoplastic human pituitary: evidence of a regulatory role for leptin on pituitary cell proliferation. J Clin Endocrinol Metab, 94, 2903-2911

Kölsch, V., Seher, T., Fernandez-Ballester, G. J., Serrano, L., & Leptin, M. (2007). Control of Drosophila gastrulation by apical localization of adherens junctions and RhoGEF2. Science, 315(5810), 384-386.‏

Lammert, A., Kiess, W., Bottner, A., Glasow, A. & Kratzsch, J. (2001). Soluble leptin receptor represents the main leptin binding activity in human blood. Biochem Biophys Res Commun, 283(4), 982-8

Lane, P. H. & Dickie, M. (1954). Fertile, obese male mice. J Hered, 4556-58.

Latchoumycandane, C., Chitra, K. C. & Mathur, P. P. (2002). The effect of methoxychlor on the epididymal antioxidant system of adult rats. Reprod Toxicol, 16(2), 161-72.

Lonnqvist, F., Arner, P., Nordfors, L. & Schalling, M. (1995). Overexpression of the obese (ob) gene in adipose tissue of human obese subjects. Nat Med, 1(9), 950-3.

Lonnqvist, F., Wennlund, A. & Arner, P. (1997). Relationship between circulating leptin and peripheral fat distribution in obese subjects. Int J Obes Relat Metab Disord, 21(4), 255-60.

Maffei, M., Halaas, J., Ravussin, E., Pratley, R. E., Lee, G. H., Zhang, Y., Fei, H., Kim, S., Lallone, R., Ranganathan, S. & et al. (1995). Leptin levels in human and rodent: measurement of plasma leptin and ob RNA in obese and weight-reduced subjects. Nat Med, 1(11), 1155-61.

Maffei, M., Halaas, J., Ravussin, E., Pratley, R. E., Lee, G. H., Zhang, Y., Fei, H., Kim, S., Lallone, R., Ranganathan, S. & et al. (1995). Leptin levels in human and rodent: measurement of plasma leptin and ob RNA in obese and weight-reduced subjects. Nat Med, 1(11), 1155-61.

McCann, S. M., Kimura, M., Walczewska, A., Karanth, S., Rettori, V. & Yu, W. H. (1998). Hypothalamic control of FSH and LH by FSH-RF, LHRH, cytokines, leptin and nitric oxide. Neuroimmunomodulation, 5(3-4), 193-202.

Mounzih, K., Lu, R. & Chehab, F. F. (1997). Leptin treatment rescues the sterility of genetically obese ob/ob males. Endocrinology, 138(3), 1190-3

Ogawa, Y., Masuzaki, H., Isse, N., Okazaki, T., Mori, K., Shigemoto, M., Satoh, N., Tamura, N., Hosoda, K., Yoshimasa, Y. & et al. (1995). Molecular cloning of rat obese cDNA and augmented gene expression in genetically obese Zucker fatty (fa/fa) rats. J Clin Invest, 96(3), 1647-52.

Oswal, A. & Yeo, G. S. (2007). The leptin melanocortin pathway and the control of body weight: lessons from human and murine genetics. Obes Rev, 8(4), 293-306

Parent, A. S., Lebrethon, M. C., Gerard, A., Vandersmissen, E. & Bourguignon, J. P. (2000). Leptin effects on pulsatile gonadotropin releasing hormone secretion from the adult rat hypothalamus and interaction with cocaine and amphetamine regulated transcript peptide and neuropeptide Y. Regul Pept, 92(1-3), 17-24.

Popovic V, Damjanovic S, Dieguez C, Casaneuva FF, (2001) Leptin and the pituitary. Pituitary 4, 714.

Popović, M., Matana, A., Torlak, V., Boutin, T., Brdar, D., Gunjača, I., ... & Zemunik, T. (2019). Genome-wide meta-analysis identifies novel loci associated with free triiodothyronine and thyroid-stimulating hormone. Journal of Endocrinological Investigation, 42(10), 1171-1180.‏

Ravussin, E., & Bogardus, C. (2000). Energy balance and weight regulation: genetics versus environment. British Journal of Nutrition, 83(S1), S17-S20.‏

Russell, L. D., Kershaw, M., Borg, K. E., El Shennawy, A., Rulli, S. S., Gates, R. J. & Calandra, R. S. (1998). Hormonal regulation of spermatogenesis in the hypophysectomized rat: FSH maintenance of cellular viability during pubertal spermatogenesis. J Androl, 19(3), 308-19; discussion 341-2.

Seeley, R. J., van Dijk, G., Campfield, L. A., Smith, F. J., Burn, P., Nelligan, J. A., Bell, S. M., Baskin, D. G., Woods, S. C. & Schwartz, M. W. (1996). Intraventricular leptin reduces food intake and body weight of lean rats but not obese Zucker rats. Horm Metab Res, 28(12), 664-8.

Somasunder P, Yu AK, Vona-Davis L, McFadden DW (2003) Differential effects of leptin on cancer in vitro. J Surg Res 113:50-55

Spicer, L. J. & Francisco, C. C. (1997). The adipose obese gene product, leptin: evidence of a direct inhibitory role in ovarian function. Endocrinology, 138(8), 33749.

Tena-Sempere, M., Pinilla, L., Gonzalez, L. C., Navarro, J., Dieguez, C., Casanueva, F. F. & Aguilar, E. (2000). In vitro pituitary and testicular effects of the leptin-related synthetic peptide leptin(116-130) amide involve actions both similar to and distinct from those of the native leptin molecule in the adult rat. Eur J Endocrinol, 142(4), 410.

Tena-Sempere, M., Pinilla, L., Zhang, F. P., Gonzalez, L. C., Huhtaniemi, I., Casanueva, F. F., Dieguez, C. & Aguilar, E. (2001). Developmental and hormonal regulation of leptin receptor (Ob-R) messenger ribonucleic acid expression in rat testis. Biol Reprod, 64(2), 634-43.

Tezuka, M., Irahara, M., Ogura, K., Kiyokawa, M., Tamura, T., Matsuzaki, T., Yasui, T. & Aono, T. (2002). Effects of leptin on gonadotropin secretion in juvenile female rat pituitary cells. Eur J Endocrinol, 146(2), 261-6

Tritos, N. A. & Mantzoros, C. S. (1997). Leptin: its role in obesity and beyond. Diabetologia, 40(12), 1371-9

Urbanski HF. (2001) Leptin and puberty. Trends in Endocrinology and Metabolism 12, 428-429.

Vidal S, Cohen SM, Horvath E, kovacs K, Scheithauer BW, Burguera BG, Lloyd RV (2000) Subcellular localization of leptin in non-tumorous and adenomatous human oituitaries: an immuno-ultrastructural study. J Histochem Cytochem. 48,1147-1152

Wang, X., Zhang, X., Hu, L., & Li, H. (2018). Exogenous leptin affects sperm parameters and impairs blood testis barrier integrity in adult male mice. Reproductive Biology and Endocrinology, 16(1), 111.‏

Woller, M., Tessmer, S., Neff, D., Nguema, A. A., Roo, B. V. & Waechter-Brulla, D. (2001). Leptin stimulates gonadotropin releasing hormone release from cultured intact hemihypothalami and enzymatically dispersed neurons. Exp Biol Med

Zamorano, P. L., Mahesh, V. B., De Sevilla, L. M., Chorich, L. P., Bhat, G. K. & Brann, D. W. (1997). Expression and localization of the leptin receptor in endocrine and neuroendocrine tissues of the rat. Neuroendocrinology, 65(3), 223-8.

Downloads

Published

2023-01-04

Issue

Section

ARTICLE