Vieira Milene Leivas, Costa Nathália Orlandini, Pereira Marina Rangel F, de Fátima Paccola Mesquita Suzana, Moreira Estefânia Gastaldello, Gerardin Daniela Cristina Ceccatto
Department of Physiological Sciences, State University of Londrina, 86051-980, Londrina, Paraná, Brazil.
Department of Biology, State University of Londrina, 86051-980, Londrina, Paraná, Brazil.
Toxicology. 2017 Aug 15;389:85-93. doi: 10.1016/j.tox.2017.07.012. Epub 2017 Jul 22.
Several studies have suggested that propiconazole (PROP) may be an endocrine disruptor; possibly altering the activity of the CYP51 enzyme, which is part of the cholesterol biosynthesis pathway required for the production of sexual steroid hormones. Another PROP effect is inhibition of the aromatase enzyme that converts androgens into estrogens, which could lead to negative effects on reproductive parameters. Therefore, the present study evaluated the reproductive and developmental toxicity of PROP by exposing two generations (F1 and F2) of male rats to this fungicide, since a previous study from our lab reported that PROP has anti-estrogenic and anti-androgenic activities (Costa et al., 2015) in the male parental (P) generation. The F1 males were exposed to PROP (4 or 20mg/kg) through germ cells (via the P generation), intra uterus, and lactation, following treatment by gavage from post-natal day (PND) 21 to 120, while the F2 generation was exposed through germ cells, intra uterus, and lactation. The parameters observed in both F1 and F2 generations were: body weight, anogenital distance (PND 0 and 21), ontogenic reflex, testosterone plasmatic levels, testis weight, and testicular histomorphology (PND 21); and in the F1 generation only: preputial separation (PND 40), sexual behavior, organ weights, testosterone and estradiol plasmatic levels (PND 120), sperm count and morphology, and testicular histomorphology at adulthood. In the F1 and F2 generations, PROP (4mg/kg) presented a decrease in testosterone levels, and in the F1 decreases in the vas deferens weight, without hormonal and functional changes of the reproductive organs, either at 4mg/kg or at 20mg/kg, in adulthood. Based on the results of this work, PROP did not alter the gonadal-endocrine parameters under these exposure conditions in rats.
多项研究表明，丙环唑（PROP）可能是一种内分泌干扰物；它可能改变CYP51酶的活性，而CYP51酶是性甾体激素产生所需的胆固醇生物合成途径的一部分。丙环唑的另一个作用是抑制将雄激素转化为雌激素的芳香化酶，这可能对生殖参数产生负面影响。因此，本研究通过让两代（F1和F2）雄性大鼠接触这种杀菌剂来评估丙环唑的生殖和发育毒性，因为我们实验室之前的一项研究报告称，丙环唑在雄性亲代（P）代中具有抗雌激素和抗雄激素活性（Costa等人，2015年）。F1代雄性大鼠从出生后第21天（PND）到120天通过灌胃接受丙环唑（4或20mg/kg）处理，通过生殖细胞（经由P代）、子宫内和哺乳期接触该药剂，而F2代则通过生殖细胞、子宫内和哺乳期接触。在F1和F2代中观察的参数包括：体重、肛门生殖器距离（PND 0和21）、个体发育反射、血浆睾酮水平、睾丸重量和睾丸组织形态学（PND 21）；仅在F1代中观察的参数包括：包皮分离（PND 40）、性行为、器官重量、血浆睾酮和雌二醇水平（PND 120）、精子计数和形态以及成年期睾丸组织形态学。在F1和F2代中，丙环唑（4mg/kg）使睾酮水平降低，在F1代中使输精管重量降低，在成年期，无论是4mg/kg还是20mg/kg剂量下，生殖器官均无激素和功能变化。基于这项工作的结果，在这些暴露条件下，丙环唑未改变大鼠的性腺内分泌参数。
