Colbert Nathan K W, Pelletier Nicole C, Cote Joyce M, Concannon John B, Jurdak Nicole A, Minott Sara B, Markowski Vincent P
Maine Center for Toxicology and Environmental Health, University of Southern Maine, Portland, Maine 04104-9300, USA.
Environ Health Perspect. 2005 Jun;113(6):700-7. doi: 10.1289/ehp.7509.
In this study we examined the effects of exposure to the antiandrogenic fungicide vinclozolin (Vz) on the development of two sex-differentiated behaviors that are organized by the perinatal actions of androgens. Pregnant Long-Evans rats were administered a daily oral dose of 0, 1.5, 3, 6, or 12 mg/kg Vz from the 14th day of gestation through postnatal day (PND)3. The social play behavior of juvenile offspring was examined on PND22 and again on PND34 during play sessions with a same-sex littermate. After they reached adulthood, the male offspring were examined with the ex copula penile reflex procedure to assess erectile function. Vz did not produce any gross maternal or neonatal toxicity, nor did it reduce the anogenital distance in male pups. We observed no effects of Vz on play behavior on PND22. However, the 12-mg/kg Vz dose significantly increased play behavior in the male offspring on PND34 compared with controls. The most dramatic increases were seen with the nape contact and pounce behavior components of play. The Vz effect was more pronounced in male than in female offspring. As adults, male offspring showed a significant reduction of erections at all dose levels during the ex copula penile reflex tests. The 12-mg/kg dose was also associated with an increase in seminal emissions. These effects demonstrate that perinatal Vz disrupts the development of androgen-mediated behavioral functions at exposure levels that do not produce obvious structural changes or weight reductions in androgen-sensitive reproductive organs.
在本研究中,我们研究了接触抗雄激素杀菌剂乙烯菌核利(Vz)对两种由雄激素围产期作用所组织的性别分化行为发育的影响。从妊娠第14天到出生后第3天(PND3),对怀孕的Long-Evans大鼠每日口服0、1.5、3、6或12mg/kg的Vz。在PND22以及与同性同窝仔鼠玩耍期间的PND34,对幼年后代的社会玩耍行为进行了检查。成年后,对雄性后代进行阴茎交配后反射程序检查以评估勃起功能。Vz未产生任何明显的母体或新生儿毒性,也未缩短雄性幼崽的肛门与生殖器之间的距离。我们观察到Vz对PND22时的玩耍行为没有影响。然而,与对照组相比,12mg/kg的Vz剂量显著增加了PND34时雄性后代的玩耍行为。在玩耍的颈背接触和猛扑行为成分中观察到最显著的增加。Vz对雄性后代的影响比对雌性后代更明显。成年后,在阴茎交配后反射测试中,所有剂量水平的雄性后代勃起均显著减少。12mg/kg的剂量还与射精增加有关。这些影响表明,围产期接触Vz会破坏雄激素介导的行为功能的发育,而此时接触水平并未在雄激素敏感的生殖器官中产生明显的结构变化或体重减轻。