Dioxins and Male Pubertal Growth and Development

说明(由申请人提供)：据报道，女孩和男孩都有青春期开始年龄提前的时间趋势。尽管青春期发病年龄变化的具体原因尚未明确，但环境化学物质以及营养过剩和肥胖对生殖轴的影响都被认为是潜在的因素。令人关注的环境化学品是一类化合物，包括多氯二苯并对二恶英、二苯并呋喃和多氯联苯。这些化合物是实验室动物和有限的人类研究中的生殖和发育毒素。在建议的应用中，我们针对的是俄罗斯查帕夫斯克的一个人口，这是一个工业城镇，有文件证明环境中二恶英和多氯联苯的水平很高。我们建议前瞻性地延长对550名8至9岁男孩的跟踪调查，其中我们正在调查二恶英和多氯联苯与以下因素的关系：1)青春期发育的时间和节奏；2)线性生长、体重增加、身体成分(体脂百分比)和身体质量指数；以及3)调节生长和青春期发育的激素的生化变化。在招募时，进行基线检查，包括生长和青春期发育的生理和生理标志。物理标记包括拟人化测量和通过Tanner确定青春期成熟，生殖器和阴毛发育的分期，以及睾丸体积的评估。生理标志物包括下丘脑-垂体-性腺轴的生化指标，通过血清促性腺激素(卵泡刺激素和黄体生成素)、性类固醇、抑制素-B和米勒抑制物质以及调节身体生长和代谢的激素，如甲状腺素、促甲状腺激素、瘦素和胰岛素样生长因子-1进行评估。从男童和他们的母亲身上采集血液样本，进行二恶英和多氯联苯分析。改变生长和青春期发育的化学物质对儿童和成人健康都有重大的临床和公共卫生影响。生长发育改变的具体影响包括生育力受损，肥胖风险增加，以及行为和心理障碍的风险。这项拟议的研究是独一无二的，因为它将是探索二恶英和多氯联苯与青春期前男孩生长发育关系的首批大型纵向研究之一。

DESCRIPTION (provided by applicant): A temporal trend towards an earlier age of onset of puberty has been reported in both girls and boys. Although specific etiologies have not been clearly identified for this reported change in the age of pubertal onset, the effects of environmental chemicals as well as that of overnutrition and obesity on the reproductive axis have both been implicated as potential factors. Environmental chemicals of concern are a family of compounds that includes polychlorinated dibenzo-p-dioxins, dibenzofurans and polychlorinated biphenyls. These compounds are reproductive and developmental toxins in laboratory animals and in limited human studies. In the proposed application, we target a population in Chapaevsk, Russia, an industrial town that has high documented environmental levels of dioxins and PCBs. We propose to prospectively extend follow-up of our cohort of 550 eight- to nine-year old boys, in which we are investigating the association of dioxins and PCBs with: 1) the timing and tempo of pubertal development; 2) linear growth, weight gain, body composition (per cent body fat), and body mass index; and 3) biochemical changes in hormones that regulate growth and pubertal development. At recruitment, baseline examinations are performed that include physical and physiologic markers of growth and pubertal development. Physical markers include anthropomorphic measurements and determination of pubertal maturation by Tanner staging for genital and pubic hair development and assessment of testicular volume. Physiological markers consist of biochemical measures of the hypothalamic-pituitary-gonadal axis, assessed by serum gonadotropins (follicle-stimulating hormone and luteinizing hormone), sex steroids, inhibin-B and Mullerian inhibiting substance, as well as hormones that regulate somatic growth and metabolism, such as thyroxine, thyroid stimulating hormone, leptin, and insulin- like growth factor-1. Blood samples are collected from the boys and their mothers for dioxin and PCB analysis. Chemicals that alter growth and pubertal development have significant clinical and public health implications for both childhood and adult health. Specific implications of altered growth and development include impaired fertility, increased risk of obesity, and risk of behavioral and psychological disorders. The proposed study is unique since it will represent one of the first large longitudinal studies to explore the relationship of dioxins and PCBs with growth and development in pre-pubertal boys.