Intraperitoneal kisspeptin-10 administration induces dose-dependent degenerative changes in maturing rat testes

• Published in: Life sciences (1973) Vol. 88; no. 5-6; pp. 246 - 256
• Main Authors: Ramzan, Faiqah, Qureshi, Irfan Zia
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 31-01-2011
• Subjects: acrosome; Animals; Dose-Response Relationship, Drug; electron microscopy; follicle-stimulating hormone; giant cells; Hypothalamic-pituitary-gonadal axis; Injections, Intraperitoneal; Kisspeptin; Kisspeptins; luteinizing hormone; Male; males; Metastin; mitosis; necrosis; neurons; Organ Size - drug effects; pachytene stage; Prepubertal testes; puberty; radioimmunoassays; Rats; Seminiferous tubules; Sertoli cells; Sexual Maturation - drug effects; spermatids; spermatocytes; Spermatogenesis; spermatogonia; Testis - drug effects; testosterone; Tumor Suppressor Proteins - administration & dosage; Tumor Suppressor Proteins - pharmacology; Kisspeptin; Hypothalamic-pituitary-gonadal axis; Seminiferous tubules; Metastin; Prepubertal testes; Spermatogenesis
• ISSN: 0024-3205; 1879-0631
• DOI: 10.1016/j.lfs.2010.11.019

Kisspeptin, a peptide secreted by hypothalamic neurons, is a critical regulator of reproduction and puberty but its role in the regulation of gonadal maturation in sexually immature males is elusive. The present study investigated the effects of 12days of pulsatile kisspeptin administration on gonadotropins and testosterone release and maturation of immature male gonads.
Kisspeptin-10 was administered intraperitoneally at different dosage concentrations (1μg, 1ng, and 10pg) to 5weeks old prepubertal male rats, twice daily for 12days. Plasma LH, FSH and testosterone concentrations were measured through competitive-binding radioimmunoassay. Spermatogenesis was studied mainly at stage VII of the spermatogenic cycle through light and electron microscopy.
At the end of the treatments plasma LH and testosterone concentrations were reduced significantly at 1ng and 1μg kisspeptin doses (P<0.05; P<0.01). Type A spermatogonia, preleptotene spermatocytes, pachytene spermatocytes, step 7 spermatids, elongated spermatids and daily sperm production decreased significantly (P<0.05). Sertoli cell efficiency and total support capacity of Sertoli cells were reduced at all doses (P<0.05). Meiotic index decreased (P<0.05) at 1μg dose only, whereas coefficient of mitosis increased at 1ng and 1μg (P<0.01) kisspeptin doses. Histologically, degeneration of seminiferous tubules was evident showing tubular necrosis, multinucleated giant cell formation, intratubular vacuolization, widened lumen and deshaped germ cells. Marked ultrastructural changes characterized by thin basal laminae, enlarged intratubular spaces, abnormal acrosome and disrupted germ cells were noticeable.
In conclusion long-term kisspeptin-10 administration negatively regulates gonadal maturation in prepubertal testes.