Kita Diogo H, Meyer Katlyn B, Venturelli Amanda C, Adams Rafaella, Machado Daria L B, Morais Rosana N, Swan Shanna H, Gennings Chris, Martino-Andrade Anderson J
Department of Physiology, Division of Biological Sciences, Federal University of Paraná, Curitiba, Paraná, Brazil.
Department of Preventive Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Toxicology. 2016 Aug 10;368-369:152-161. doi: 10.1016/j.tox.2016.08.021. Epub 2016 Sep 14.
We examined the anogenital distance (AGD) plasticity in rats through the manipulation of the androgen environment in utero and during puberty. Dams were treated from gestation days 13-20 with vehicle, flutamide (20mg/kg/day), di-(2-ethylhexyl) phthalate (DEHP, 750mg/kg/day), or testosterone (1.0mg/kg/day). After weaning, male pups were randomly assigned to one of four postnatal groups, which received the same treatments given prenatally. Sixteen treatment groups were established based on the combination of pre- and postnatal exposures. The postnatal treatments were conducted from postnatal days 23-53. In utero flutamide and DEHP exposure significantly shortened male AGD, although this effect was more pronounced in flutamide-exposed rats. Postnatal flutamide, DEHP, and testosterone induced slight but significant reductions in male AGD. Our study indicates that AGD is a stable anatomical landmark that reflects the androgen action in utero, although it can also be slightly responsive to changes in the androgen environment following pubertal exposure.
我们通过在子宫内和青春期对雄激素环境进行操控,研究了大鼠的肛门生殖器距离(AGD)可塑性。从妊娠第13至20天起,对孕鼠分别给予溶剂、氟他胺(20毫克/千克/天)、邻苯二甲酸二(2-乙基己基)酯(DEHP,750毫克/千克/天)或睾酮(1.0毫克/千克/天)进行处理。断奶后,将雄性幼崽随机分配到四个出生后组之一,这些组接受与产前相同的处理。根据产前和产后暴露的组合建立了16个处理组。产后处理在出生后第23至53天进行。子宫内暴露于氟他胺和DEHP会显著缩短雄性AGD,不过这种效应在暴露于氟他胺的大鼠中更为明显。出生后暴露于氟他胺、DEHP和睾酮会导致雄性AGD出现轻微但显著的降低。我们的研究表明,AGD是一个稳定的解剖学标志,反映了子宫内的雄激素作用,但它对青春期暴露后雄激素环境的变化也可能有轻微反应。