THE INFLUENCE OF CHLOROQUINE PHOSPHATE ON MALE REPRODUCTIVE FUNCTIONS

Abstract

The influence of Chloroquine phosphate on Male reproductive functions in the adult and pre-pubertal rats was studied. Chloroquine phosphate dissolved in distilled water was administered intraperitoneally daily to the rats at two dosage levels of 5mg base/kg body weight and 10mg base/kg body weight for a period of one week and two weeks. Chloroquine with its metabolites was measured in whole blood, testis and epididymis of the rats by a sensitive spectrofluorimetric method. Fertility of the adult male rats was assessed by an isolated mating technique; in which each male rat was separately caged and mated with three female rats. The litter size of the female rat; as well as number of resorption sites was used as index of fertilizing capability of the male rats. Circulating testosterone level was measured by a radioimmunoassay technique; while the cross sections of the seminiferous epithelium were classified according to their phases of spermatogenesis. Chloroquine at the dosages administered for the period of study did not affect body, testicular nor epididymal weights compared to the controls of both the adult and pre-pubertal groups. The drug was concentrated in the testis and epididymis in a dose-related manner. Testicular Chloroquine levels were higher in the pre-pubertal group compared to the adult group. The epididymal Chloroquine levels were however generally lower in the pre-pubertal than the rats while whole blood Chloroquine levels were similar in both the pre-pubertal and adult age. These findings suggest; an age-related difference in the binding capacity of the tissues for Chloroquine. Fertility of the male rats to which Chloroquine was administered was reduced in a dose-related manner although caudal epididymal sperm-count was not significantly affected. This indicates that Chloroquine adversely affects the fertilizing capability of the epididymal sperms without a reduction in sperm number. The histology of the testis was normal in both the Chloroquine administered and control groups of rats. However, certain cellular generations were absent or unduly subsit in the testis of the rats to which Chloroquine was administered compared to controls. Circulating testosterone levels were lower in the Chloroquine-administered group compared to the controls: a finding particularly evident in the pre-pubertal group; suggesting steriodogenesis to be more adversely affected by Chloroquine in the pre-pubertal rats. Chloroquine was detected in human semen 24hrs after ingestion of the drug and also in semen of volunteers who claimed not to have taken the drug in the preceding four months to study, suggesting the drug is stored within the male reproductive system for long periods. In vitro, Chloroquine enhanced human sperm performance that is ; viability, force of forward progression and percentage of motile sperms when added into the incubating medium at low concentrations (15 x 10⁻⁶M). Enhancement of sperm activity by Chloroquine may be mediated by the intrasperm content of cAmp: leading to the accumulation of the cyclic nucleotides within the sperm cells.