Reproductive Disorders in Pubertal and Adult Phase of the Male Rats Exposed to Vinclozolin during Puberty

Abstract

ABSTRACT. Vinclozolin (VCZ) is a systemic dicarboximide fungicide with antiandrogenic activity. Reproductive toxicity of VCZ was investigated in male rats exposed to VCZ during puberty. Sprague-Dawley male rats aged with 35 days were assigned to six different groups; negative control, positive control receiving flutamide (100 mg/kg), VCZ (100, 200 and 400 mg/kg), and a combination of VCZ (200 mg/kg) + methyltestosterone (100 mg/kg). The animals were treated with test compounds by oral gavage daily during 35 to 44 days of age. In pubertal rats sacrificed on the next day after final treatment, VCZ or flutamide-treated group showed a decrease in weights of prostate, epididymis, and seminal vesicle, hypertrophy of Leydig cells in the testis, detached debris and sloughed cells in the tubules of the caput epididymis, and an increase in serum testosterone levels. On the other hand, combined treatment of VCZ + methyltestosterone decreased testicular weight, increased seminal vesicle weight, and induced degeneration of spermatocytes. In adult rats sacrificed at five weeks after final treatment, flutamide decreased testicular sperm counts, and VCZ, flutamide and VCZ + methyltestosterone also decreased epididymal sperm counts. In addition, treatment of VCZ (400 mg) or VCZ + methyltestosterone decreased some motion kinematic parameters of sperms including curvilinear velocity, mean angular displacement and lateral head displacement. Flutamide treatment also decreased lateral head displacement. These results indicate that VCZ exposure during pubertal period in male rats causes reproductive disorders in puberty and adulthood. KEY WORDS: flutamide, serum testosterone, sperm count, sperm motility, vinclozolin.J. Vet. Med. Sci. 66 (7): [847][848][849][850][851][852][853] 2004 Vinclozolin (VCZ), a systemic dicarboximide fungicide, has been used in the control of diseases caused by Botrytis cinerea, Sclerotinia sclerotiorum, Rhizoctonia solani and Moniliniam spp in grapes, fruits, vegetables, hops, ornamental plants, and turf grasses [10]. VCZ is also used for esculent plant cultivation in many countries including Korea, United States, Europe and etc. Fungicide effect of VCZ appears to be exerted by inhibiting ergosterol synthesis [10] and by inducing lipid peroxidation via oxygen activation in fungi [2]. VCZ is metabolized to M1 and M2 that remain commonly in the soil, the plants, and mammals. Although VCZ itself is a very weak antagonist for androgen receptor binding, both M1 and M2 are effective antagonists [4]. In addition, M1 and M2 inhibited androgen-induced transactivation mediated by a mouse mammary tumor virus promoter [12].VCZ exposure to mother rats during periparturition period caused persistent nipples, cleft phallus with hypospadias, female-like anogenital distance, suprainguinal ectopic scrota/testes, a vaginal pouch, epididymal granulomas, small to absent accessory sex glands in male offsprings, and sexual intercourse failure with mating-proven female adult rats [3]. An exposure of VCZ from weaning to early adul...

An Organophosphate Insecticide Methyl Parathion (O- O- Dimethyl O-4-Nitrophenyl Phosphorothioate) Induces Cytotoxic Damage and Tubular Atrophy in the Testis Despite Elevated Testosterone Level in the Rat

“…This action of MP partly is in consensus with that of flutamide or vinclozolin, in which testosterone level increased due to suppression of feed-back inhibition of androgens on the anterior pituitary (O'Connor et al, 1998). The suppression of feedback inhibition may secondarily increase the LH secretion and a blockade of Leydig cell androgen receptors, leading to increased secretion of testosterone (Andrews et al, 2001;Yu et al, 2004). However, in the present study, the LH level was also decreased in the treated testis, indicating a direct effect on the anterior pituitary.…”

“…In the present study also, Leydig cells maintained normal structure, although testosterone level increased. In general, antiandrogens induce structural changes in the testis, characterized by hypertrophy of Leydig cells (Andrews et al, 2001;Yu et al, 2004). In the present study, changes in the testicular structure were observed, although Leydig cells were normal, thus making a difference with a typical anti-androgen.…”

Endocrine disruptors and prostate cancer risk

“…Since vinclozolin effects are driven through AR antagonism, it is not surprising that there are no reported associations between this compound and prostate cancer, an androgen-dependent disease. Exposure of rats to vinclozolin during development results in reduced prostate gland growth and size which would be expected for an anti-androgen (Yu et al 2004). Of interest, however, are recent studies with maternal (i.e.…”

Semen quality trends in French regions are consistent with a global change in environmental exposure

“…Fungicides are by far the most employed but there are important disparities of practices among the French wineyielding regions (Ambiaud 2012). For example, vinclozolin is well known for its action on male fertility (Yu et al 2004), even at early low-dose exposure (Eustache et al 2009, Auger et al 2010. This peculiar fungicide product, acting as an anti-androgen, was widely used in grapevine, fruit, and vegetable cultures from 1978 to 2007 in France, and is also increasingly suspected to have transgenerational effects (Auger et al 2013, Skinner et al 2013.…”