Effect of the anti-androgenic endocrine disruptor vinclozolin on embryonic testis cord formation and postnatal testis development and function.
Vinclozolin is a systemic dicarboximide fungicide that is used on fruits, vegetables, ornamental plants, and turf grass. Vinclozolin and its metabolites are known to be endocrine disruptors and act as androgen receptor antagonists. The hypothesis tested in the current study is that transient embryonic exposure to an anti-androgenic endocrine disruptor at the time of testis determination alters testis development and subsequently influences adult spermatogenic capacity and male reproduction. The effects of vinclozolin on embryonic testicular cord formation in vitro were examined, as well as the effects of transient in utero vinclozolin exposure on postnatal testis development and function. Embryonic day 13 (E13, sperm-positive vaginal smear day = E0) gonads were cultured in the absence or presence of vinclozolin (50-500microM). Vinclozolin treated gonads had significantly fewer cords (P < 0.05) and the histology of the cords that formed were abnormal as compared to vehicle-treated organs. Pregnant rats were exposed to vinclozolin (100 mg/kg/day) between embryonic days 8 and 14 (E8-E14) of development. Testis morphology and function were analyzed from postnatal day (P) 0, pubertal P20, and adult P60. No significant effect of vinclozolin on testis histology or germ cell viability was observed in P0 testis. The pubertal P20 testis from vinclozolin exposed animals had significantly higher numbers of apoptotic germ cells (P < 0.01), but testis weight was not affected. The adult P60 sperm motility was significantly lower in vinclozolin exposed males (P < 0.01). In addition, apoptotic germ cell number in testis of vinclozolin exposed animals was higher in adult P60 animals. Observations demonstrate that vinclozolin can effect embryonic testicular cord formation in vitro and that transient in utero exposure to vinclozolin increases apoptotic germ cell numbers in the testis of pubertal and adult animals. This correlated to reduced sperm motility in the adult. In conclusion, transient exposure to vinclozolin during the time of testis differentiation (i.e. cord formation) alters testis development and function. Observations indicate that transient exposure to an anti-androgenic endocrine disruptor during embryonic development causes delayed effects later in adult life on spermatogenic capacity.
Center for Reproductive Biology, School of Molecular Biosciences, Washington State University, Pullman, WA 99164-4231, USA.
Mehmet
M
Uzumcu
Hiroetsu
H
Suzuki
Michael K
MK
Skinner
D000726:Androgen Antagonists / Q000633:toxicity*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D004396:Coloring Agents; D004801:Eosine Yellowish-(YS); D005260:Female; D005298:Fertility / Q000187:drug effects; D005485:Flutamide / Q000633:toxicity; D005659:Fungicides, Industrial / Q000633:toxicity*; D006416:Hematoxylin; D008297:Male; D009924:Organ Culture Techniques; D010080:Oxazoles / Q000633:toxicity*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D012671:Seminiferous Tubules / Q000187:drug effects / Q000196:embryology; D013076:Sperm Count; D013091:Spermatogenesis / Q000187:drug effects; D013737:Testis / Q000187:drug effects* / Q000196:embryology / Q000254:growth & development*
D000726:Androgen Antagonists; D004396:Coloring Agents; D005659:Fungicides, Industrial; D010080:Oxazoles; D005485:Flutamide; C025643:vinclozolin; D004801:Eosine Yellowish-(YS); D006416:Hematoxylin