Previous studies have shown that a single intratesticular injection wi
th 70% glycerol results in rapid and long-term suppression of spermato
genesis. Because of the extensive testicular damage in the form of foc
al destruction and large numbers of acellular seminiferous tubules, it
was difficult to examine the possible chemical mechanisms of antisper
matogenic action. Our objective was to explore regimens of treatment t
hat would result in significant suppression of spermatogenesis without
significant testicular damage. Sexually mature Sprague-Dawley rats we
re injected intratesticularly with various glycerol concentrations (0,
10, 20, 40, or 70%) and with volumes of either 200 or 350 mu l per te
stis. At times between 1 and 36 weeks after the injection, the effect
on weights of testes and accessory sex organs, testicular histology, s
perm numbers, serum hormonal levels, and gonadotropin-receptor binding
was examined. An injection of 350 mu l/testis of a 10% glycerol solut
ion led to a significant decrease in weights of testes and epididymide
s. The treatment resulted in an overall suppression of spermatogenesis
, with about 90% fewer sperm in the epididymides than in control anima
ls. Histologically, the treatment decreased the number of normal tubul
es from 97% (control) to 16% and resulted in testes in which about 75%
of the tubules were aspermatogenic (containing only Sertoli cells and
spermatogonia). The number of acellular tubules (tubules without cyto
logical detail) was generally less than 5% of the total, and there was
negligible focal destruction. Serum levels of gonadotropins and andro
gens were not altered significantly by the treatment, and Sertoli cell
glutamyl transpeptidase activity appeared normal. An equi-osmolar sol
ution of glucose also resulted in significant suppression of spermatog
enesis, but the effect of glycerol was significantly greater, suggesti
ng a mechanism in addition to hyperosmolarity. This study, therefore,
is further evidence for the specificity of glycerol actions and for it
s potential as an antispermatogenic agent.