Dose Dependent Degeneration of Leydig Cells Following Kisspeptin-10 Administration: An Ultrastructural Study
Background: The discovery of kisspeptin signaling as a key regulator of gonadotropin releasing hormone (GnRH) secretion from the hypothalamus enhanced our understanding of the neuroendocrine regulation of mammalian reproduction. Effects of central and peripheral administration of kisspeptin on plasma gonadotropins, testosterone and spermatogenesis are studied in detail. Objective: The present study was conducted to check the ultrastructure of Leydig cells in prepubertal male rats in response to the administration of a range of kisspeptin doses. Method: To this end, we administered a range of kisspeptin-10 doses (1µg, 1ηg and 10ρg) intraperitoneally, to prepubertal male Sprague-Dawley rats (PND 35) twice daily after every 12 hours. Control rats were injected with physiological saline in parallel. Results: At the end of the treatment, plasma concentrations of testosterone was measured by competitive binding radioimmunoassay and small pieces of rat testicular tissue were processed for electron microscopy to examine the ultrastructure of Leydig cells. Plasma testosterone concentration was reduced significantly at 1ηg (P<0.05) and 1μg (P<0.01) doses as compared to control. Distinct ultrastructural changes categorized as dilatation of cytoplasmic organelles, irregular shaped nuclei with nuclear membrane invaginations, reduced nuclear sizes, degeneration and vacuolation were observed in the kisspeptin-10 treated Leydig cells as compared to control. Quantification of the data showed reduced Leydig cell indices and hyperplasia of the interstitial cells. Conclusion: It is concluded that chronic intermittent administration of kisspeptin-10 has a dose dependent degenerative effect on the plasma testosterone levels and Leydig cells ultrastructure in prepubertal male rats.