Adverse effects of chronic GnRH antagonist administration on seminiferous epithelium in adult rats.
Seminiferous epithelium in adult rats was studied by light and electron microscopy after 5 weeks of chronic administration of GnRH antagonist (Ac-D2 Nal 1, D4ClPhe 2, DTrp 3, DArg 6, DAla 10; GnRH code-103-289-10, National Institutes of Health, USA). In these rats, the epithelium showed significant accumulation of vacuoles in more than 80% of the tubules, along with germ cell degeneration and nuclear pyknosis. Disruption in the process of spermatogenesis was also very much evident. In most of the tubules studied (greater than 90%), germ cell development was arrested beyond the pachytene spermatocyte stages. The vacuoles in the seminiferous epithelium were different sizes and when magnified were seen to consist of a thickened outer margin of solid nonfibrous coat within the Sertoli cell cytoplasm. Associated changes in the interstitium showed increased intertubular space but no inflammatory type of response. In actual cell counts, the decrease in the average number of macrophages was 32% and in Leydig cells 23%, while the total number of all types of cells in the interstitium was 30% less than that of the controls. Following the treatment, weights of testis, epididymis, seminal vesicle, and ventral prostate were drastically reduced. Rats treated with testosterone supplementation (60 micrograms/rat day) to GnRH antagonist recovered testicular and epididymal weights to approximately 57% and seminal vesicle and ventral prostate weights by 82.9 and 84%, respectively. Normalcy returned to the tubular epithelium and the interstitial cell counts were restored to original levels.
Misro
M M
MM
Department of Reproductive Biomedicine, National Institute of Health and Family Welfare, New Delhi, India.
Ganguly
A
A
Das
R P
RP
D000818:Animals; D002452:Cell Count; D002467:Cell Nucleus / Q000187:drug effects / Q000648:ultrastructure; D004822:Epididymis / Q000033:anatomy & histology / Q000187:drug effects; D007987:Gonadotropin-Releasing Hormone / Q000037:antagonists & inhibitors*; D007985:Leydig Cells / Q000166:cytology; D008264:Macrophages / Q000166:cytology; D008297:Male; D009929:Organ Size / Q000187:drug effects; D011467:Prostate / Q000033:anatomy & histology / Q000187:drug effects; D051381:Rats; D012669:Seminal Vesicles / Q000033:anatomy & histology / Q000187:drug effects; D012670:Seminiferous Epithelium / Q000187:drug effects* / Q000648:ultrastructure; D013737:Testis / Q000033:anatomy & histology / Q000187:drug effects; D014617:Vacuoles / Q000187:drug effects / Q000648:ultrastructure
D007987:Gonadotropin-Releasing Hormone