O-14: Effect of Kisspeptin on Testicular Tissue and Accessory Sex Glands, Seminal Vesicle and Prostate, in Prepubertal Rats

Background: Hypothalamus-derived kisspeptins are critical regulators of reproduction in nearly all mammalian species including the humans. These small peptides mediate their actions through the GnRH loop system. How kisspeptins regulate gonadal maturation in sexually immature male mammals remains elusive. To address this, kisspeptin was administered as subchronic (12 days) twice daily i. p. doses at three different dosage regimens: 15 pmol (10 pg), 1.5 nmol (1 ng) and 1.5 μmol (1 μg), to prepubertal male Sprague Dawley rats (PND 35). Materials and Methods: Effects on spermatogenesis, secretion of testosterone and pituitary gonadotropins, the LH and FSH, DNA parameters and histomorphology of testicular tissue and accessory sex glands, seminal vesicle and prostate, were studied. Major scientific approaches applied were; radioimmunoassay, light and electron microscopy, DNA extraction, electrophoresis and morphometrical measurements. Spermatogenesis was studied histologically at stage VII of the spermatogenic cycle. Data were analyzed statistically. Results: Results showed that at end of the treatments plasma FSH levels were not altered in any of the treatment groups. LH and testosterone concentrations were reduced in the 1 ng (p < 0.05) and 1 μg kisspeptin groups (p < 0.01), while no significant change was observed at 10 pg dose. At 1 ng and 1 μg kisspeptin doses, testicular parameters that decreased significantly were mainly: the number of type A spermatogonia (p < 0.05; p < 0.01), preleptotene spermatocytes (p < 0.05), pachytene spermatocytes (p < 0.01; p < 0.001), step 7 spermatids (p < 0.05; p < 0.001), elongated spermatids and daily sperm production (p < 0.05; p < 0.001), while at 10 pg dose the decrease was non-significant. Histomorphology showed scant round and elongated spermatids, intratubular vacuolizations, multinucleated giant cells and atrophied germinal epithelium. Ultrastructure evidenced vacuolated mitochondria in Sertoli cells, involuted acrosome, degenerated and vacuolated Leydig cells and thin basal laminae. Seminal vesicle and prostate weights decreased significantly (p < 0.01) at 1 μg kisspeptin dose. The epithelial height of secretory acini of seminal vesicle and prostate decreased at 10 pg (p<0.05), 1 ng and 1μg doses (p < 0.001). Histological observations demonstrated dilated lumen and decrease in epithelial folds and height of epithelial cells. Ultrastructure showed disorganization of the organelles involved in the secretory process such as dilatation of the endoplasmic reticulum, disorganization of the Golgi complex and decrease in the number of secretory granules in principal cells with kisspeptin treatment. Percent DNA damage was significant in all tested doses. Conclusion: The present findings indicate that subchronic kisspeptin administration does not lead to an early maturation but instead it may act as a suppressor of pubertal maturation during non-pubertal states.