Dioxins and Male Pubertal Growth and Development

二恶英与男性青春期生长发育

• 批准号: 7013303
• 负责人: RUSS B HAUSER
• 金额: $ 60.06万
• 依托单位: HARVARD SCHOOL OF PUBLIC HEALTH
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-04-13 至 2011-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7013303
• 关键词: Commonwealth of Independent States; blood chemistry; blood tests; body physical characteristic; case history; child physical development; clinical research; dioxins; disease /disorder etiology; embryo /fetus toxicology; endocrine disrupting compound; environmental exposure; environmental toxicology; halobiphenyl /halotriphenyl compound; health behavior; hormone regulation /control mechanism; human puberty; human subject; hypothalamic pituitary axis; longitudinal human study; male; middle childhood (6-11); pituitary gonadal axis; precocious puberty; questionnaires; reproductive development; urinalysis; weight gain

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.

描述（由申请人提供）：据报道，男孩和男孩都报道了青春期早期的时间趋势。尽管对于青春期发作时代的这种报道的变化尚未清楚地鉴定出特定的病因，但环境化学物质以及营养和肥胖对生殖轴的影响都被视为潜在因素。令人关注的环境化学物质是包括多氯联苯 - 二氧蛋白，二苯并呋喃和多氯化双苯基的一个化合物家族。这些化合物在实验动物和有限的人类研究中是生殖和发育毒素。在拟议的应用中，我们针对俄罗斯Chapaevsk的人口，这是一个工业城镇，其二恶英和PCB的环境水平很高。我们建议将我们的550个八岁至9岁男孩的队列进行前瞻性的随访，其中我们正在调查二恶英和PCB的协会与以下方面：1）青春期发展的时机和节奏； 2）线性生长，体重增加，身体成分（体内脂肪）和体重指数； 3）调节生长和青春期发展的激素的生化变化。在招募时，进行了基线检查，其中包括生长和青春期发展的物理和生理标记。物理标记包括拟人化的测量以及通过Tanner分期确定青春期成熟的生殖和阴毛发育以及睾丸体积评估。生理标志物由下丘脑 - 垂体 - 大结构轴的生化措施组成，该轴通过血清促性腺激素（刺激性激素和黄体激素），性类固醇，抑制素-b和mullerian抑制物质以及对良好的脉络激素的刺激性生长进行评估，以及抑制素 - 抑制素-b和mullerian抑制作用，以及激素，瘦素和胰岛素喜欢生长因子1。血液样本是从男孩及其母亲那里收集的，以进行二恶英和PCB分析。改变生长和青春期发展的化学物质对童年和成人健康都具有重大的临床和公共卫生影响。改变和发展的特定含义包括生育能力受损，肥胖风险增加以及行为和心理疾病的风险。拟议的研究是独一无二的，因为它将代表探索二恶英和PCB与假伯伯纳前男孩的生长和发育关系的最早大型纵向研究之一。