The apoptotic changes of testicular germ cells in the obstructive azoospermia models of prepubertal and adult rats.
OBJECTIVE
It has been suggested that prepubertal obstruction of the seminal tract may result in irreversible damage to spermatogenesis. We examined whether accelerated apoptosis in prepubertal obstruction has a deleterious effect on spermatogenesis in adulthood.


METHODS
We studied apoptotic changes of both prepubertal and adult obstructive azoospermia rat models by means of an in situ end-labeling technique and electron microscopy, and by examination of the pathological changes. Four groups were designed as follows. Group 1: bilateral vasectomies performed at ten days of age (prepubertal vasectomy model); Group 2: sham operation performed at ten days of age; Group 3: bilateral vasectomies performed at eight weeks of age (adult vasectomy model); Group 4: sham operation performed at eight weeks of age. Three rats in each group were killed weekly, and the testes and epididymides removed and weighed. Germ cell apoptosis was detected by in situ end-labeling, and the apoptotic index (AI) was calculated by dividing the number of in situ labeled cells by the total number of seminiferous tubules. The developmental change of testis and epididymis, the diameter of seminiferous tubules, and the number of spermatogonia were also examined. Histopathological examination of tubular diameter and the number of spermatogonia and Sertoli cells was done by PAS staining. The number of spermatogonia divided by the number of Sertoli cells per tubular cross section was expressed as spermatogonia-Sertoli cell ratio (S-S ratio).


RESULTS
At 3 and 4 weeks of age, rats of group 1 demonstrated a significantly higher apoptotic index of germ cells than did the sham-operated rats of group 2 (p <0.05). No significant differences were seen between groups 3 and 4. The increased apoptosis in group 1 seemed to be reduced by the formation of epididymal granulomas. The tubular diameter of group 1 at 16 weeks of age was significantly smaller than that of groups 2, 3, or 4. The S-S ratios were lower at stages IV, V and VI in group 1 at 16 weeks-of-age following vasectomy at 10 days of age compared with that in group 2.


CONCLUSIONS
We conclude that an increase of apoptotic degeneration of germ cells in the prepubertal period may cause irreversible changes in germinal stem cells, resulting in hypospermatogenesis in adulthood.
Department of Urology, Kobe University School of Medicine, Japan.
Y
Y
Inaba
M
M
Fujisawa
H
H
Okada
S
S
Arakawa
S
S
Kamidono
D000375:Aging / Q000473:pathology*; D000818:Animals; D017209:Apoptosis; D004396:Coloring Agents; D004195:Disease Models, Animal; D004822:Epididymis / Q000473:pathology; D005832:Genital Diseases, Male / Q000150:complications; D006099:Granuloma / Q000473:pathology; D007124:Immunoenzyme Techniques; D008297:Male; D008854:Microscopy, Electron; D009845:Oligospermia / Q000209:etiology / Q000473:pathology*; D010503:Periodic Acid-Schiff Reaction; D051381:Rats; D017208:Rats, Wistar; D012669:Seminal Vesicles / Q000473:pathology*; D012671:Seminiferous Tubules / Q000473:pathology; D012708:Sertoli Cells / Q000473:pathology; D013091:Spermatogenesis; D013093:Spermatogonia / Q000473:pathology; D013094:Spermatozoa / Q000473:pathology*; D013234:Stem Cells / Q000473:pathology; D013733:Testicular Diseases / Q000473:pathology; D013737:Testis / Q000473:pathology*; D014659:Vasectomy
D004396:Coloring Agents