Intraperitoneal kisspeptin-10 administration induces dose-dependent degenerative changes in maturing rat testes.
OBJECTIVE
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 12 days of pulsatile kisspeptin administration on gonadotropins and testosterone release and maturation of immature male gonads.


METHODS
Kisspeptin-10 was administered intraperitoneally at different dosage concentrations (1 μg, 1 ng, and 10 pg) to 5 weeks old prepubertal male rats, twice daily for 12 days. 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.


RESULTS
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 1 μg dose only, whereas coefficient of mitosis increased at 1 ng and 1 μg (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.


CONCLUSIONS
In conclusion long-term kisspeptin-10 administration negatively regulates gonadal maturation in prepubertal testes.
Laboratory of Animal and Human Physiology, Department of Animal Sciences, Faculty of Biological Sciences, Quaid-i-Azam University 45320, Islamabad, Pakistan.
Faiqah
F
Ramzan
Irfan Zia
IZ
Qureshi
D000818:Animals; D004305:Dose-Response Relationship, Drug; D007274:Injections, Intraperitoneal; D059648:Kisspeptins; D008297:Male; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D012741:Sexual Maturation / Q000187:drug effects*; D013737:Testis / Q000187:drug effects*; D025521:Tumor Suppressor Proteins / Q000008:administration & dosage / Q000494:pharmacology*
C106628:KISS1 protein, human; D059648:Kisspeptins; D025521:Tumor Suppressor Proteins