Effects of ivermectin exposure in rats and rabbits: reproductive parameters

Ivermectin is a macrocyclic lactone used as a broad spectrum antiparasitic agent against nematelmints and arthropods. It is mainly used in the control of parasitic infections of domestic animals, and recently has been used in humans to treat onchocerciasis, scabies and pediculosis. In mammals, various evidences indicate that macrocyclic lactones interact with gamma-aminobutyric acid (GABA)-mediated chloride channels. It is known that the GABAergic system is involved in the manifestation of sexual behavior and previous studies have shown that ivermectin impaired sexual behavior in male and female rats. Thus, considering ivermectin may interfere with the sexual sphere, this study evaluated the temporal effects of exposure to ivermectin (0.2 and 1.0 mg/kg, administered subcutaneously) on reproductive and hormonal parameters of rats and rabbits. In rats it was evaluated organ weights of male and female, the gonadossomatic index of males, histopathological findings; the immunohistochemical of the androgen receptor in the testes; serum LH, FSH and testosterone concentrations; relative expression of steroidogenic pathway enzymes by real-time polymerase chain reaction (RT-PCR); estrous cycle, reproductive performance and estradiol concentration in the feces of female rats. In male rabbits it was evaluated the spermatozoa concentration, motility and morphology; the integrity of the membranes plasmatic, acrosomal and mitochondrial of the spermatozoa; the organ weights, the gonadosomatic index; serum testosterone concentrations; histopathological findings; and hematological and serum biochemical analysis. The results showed that ivermectin administration in rats: not alter the relative weights of the testes, epididymis, prostate and seminal vesicle; not modified gonadosomatic index; caused damage in the germinal cells of the seminiferous epithelium of the testes, finding suggestive of impairment in spermatogenesis and male spermiogenesis; did not interfere with the androgen receptor expression of the testes, as well as the relative expression of enzymes of the steroidogenic pathway; did not interfere in the serum testosterone and FSH concentrations, but it decreased the serum LH concentration; did not interfere in the estrous cycle, reproductive performance and estradiol concentration in the feces of female rats. The results of male and female rats were discussed considering the interference of ivermectin in GABAergic neurotransmission as well as in the production pathway of pituitary-gonadal hormones. In rabbits, no changes were observed in male fertility parameters evaluated by spermatozoa concentration, motility and morphology, nor the potential for fertilization evaluated by the integrity of the membranes plasmatic, acrosomal and mitochondrial of the spermatozoa; there was no interference in serum testosterone concentration, serum biochemistry and hematological parameters. These results together are indicative that ivermectin causes few adverse effects on reproductive aspects of rats and rabbits. (AU)