Dioxins and Male Pubertal Growth and Development

二恶英与男性青春期生长发育

• 批准号: 8992744
• 负责人: RUSS B HAUSER
• 金额: $ 9.38万
• 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 2016-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8992744
• 关键词: 18 year old; Adolescence; Adult; Affect; Age; Age of Onset; Aromatic Hydrocarbons; Behavioral; Body mass index; Child health care; Clinical; Cognitive; Cohort Studies; Data; Development; Dioxins; Environment; Environmental Pollution; Environmental Risk Factor; Exposure to; Family; Female; Fertility; Follicle Stimulating Hormone; Furans; Generations; Gonadal Steroid Hormones; Gonadotropins; Growth; Growth and Development function; Health; Heavy Metals; Height; Hormonal; Hormones; Human; Insulin-Like Growth Factor Binding Protein 3; Insulin-Like Growth Factor I; Laboratory Animals; Lead; Luteinizing Hormone; Measures; Mediating; Metabolic Diseases; Morphology; Obesity; Polychlorinated Biphenyls; Puberty; Public Health; Reporting; Risk; Risk Factors; Rodent; Russia; Seminal fluid; Serum; Sex Hormone-Binding Globulin; Sexual Maturation; Sperm Count Procedure; Sperm Motility; Staging; Testis; Testosterone; Thyrotropin; Thyroxine; Time; Weight Gain; boys; cohort; dibenzo(1,4)dioxin; early onset; environmental chemical; follow-up; girls; human data; inhibin B; innovation; male; next generation; nutrition; peptide hormone; polychlorinated dibenzofurans; prospective; pubertal timing; reproductive; reproductive axis; reproductive function; reproductive hormone; research study; social; sperm cell; trend

DESCRIPTION (provided by applicant): Puberty is the dynamic physical, behavioral, and hormonal transition from the pre-pubertal state to sexual maturity and adult reproductive capacity. Temporal trends towards an earlier onset of puberty have been reported particularly for girls with limited data available for boys. Although risk factors have not been clearly identified for this reported change in the age of female pubertal onset, the effects of environmental chemicals and that of over nutrition and obesity on the reproductive axis have both been implicated as potential factors. In boys, there are limited longitudinal cohort studies on the timing and progression of puberty and few studies on the impact of environmental chemicals. Environmental chemicals of particular concern for altered age of onset and progression of male puberty include chlorinated aromatic hydrocarbons, a family of highly toxic environmental contaminants that includes polychlorinated dibenzo-p- dioxins, polychlorinated dibenzofurans and polychlorinated biphenyls (PCBs), and heavy metals, specifically lead. In laboratory animals and limited human studies, dioxins, furans, PCBs and lead were shown to alter pubertal development and growth and affect adult testicular function. In this competing continuation application, we propose to prospectively extend follow-up of our cohort of 499 Russian boys through puberty and into adulthood. The boys reside in Chapaevsk, Russia, an industrial town that has documented high exposure to dioxins, furans, PCBs and lead. The specific aims are to investigate the relationship of peri-pubertal serum concentrations of dioxins, furans, PCBs and lead with: 1) progression of male pubertal development and age at attainment of sexual maturation (measured by testicular volume and Tanner stages); 2) somatic growth, specifically height, height velocity, weight gain, and BMI; 3) altered serum concentrations of hormones that regulate somatic growth and pubertal development (testosterone, inhibin- B, MIS, LH, FSH, IGF-1, IGF-BP3, TSH and free T4); 4) altered adult testis function, specifically semen quality and hormonal markers of mature testis function and the reproductive axis (testosterone, inhibin-B, LH and FSH). The proposed study is innovative because it represents one of the few large prospective cohort studies on the impact of the environment on male pubertal development, growth and reproductive function. Alterations in the timing of puberty and in growth have been shown to have adverse public health and clinical implications. For instance, altered pubertal timing adversely impacts physical and sexual maturation, social, cognitive and behavioral development in adolescence, and subsequent risk of adult obesity and metabolic disorders. Furthermore, exposure to environmental chemicals during the sensitive window of male pubertal development may adversely impact fertility and the next generation through paternally mediated effects. Therefore, the identification of potentially remediable risk factors such as exposure to dioxins, furans, PCBs and lead, is critical to both advancing our understanding of the impact of the environment on child health and protecting both child health and subsequent generations.

描述（由申请人提供）：青春期是从前伯伯塔尔州到性成熟和成人生殖能力的动态物理，行为和激素过渡。据报道，针对男孩可获得的数据有限的女孩，已经报道了较早的青春期发作的时间趋势。尽管尚未清楚地确​​定危险因素在女性青春期发作时期发生的变化，但环境化学物质的影响以及过度营养和肥胖对生殖轴的影响都被视为潜在因素。在男孩中，关于青春期的时间和进展的纵向队列研究有限，对环境化学物质的影响很少。对于雄性青春期的发生年龄和进展的改变，特别关注的环境化学物质包括氯化芳族碳氢化合物，这是一个由高毒性的环境污染物的家族，其中包括多氯化二氯二苯二甲酸，二氯二氯苯甲酰甲氟烷和多氯联苯和多氯化二苯基（PCBS），以及重心元的二氯苯基氟烷（PCBS），特定的二氯酸苯二氧化碳二氧化二氧化碳蛋白带领。在实验动物和有限的人类研究中，二恶英，Furans，PCB和铅被证明会改变青春期的发育和生长，并影响成人的睾丸功能。在此竞争性延续申请中，我们建议将我们的499名俄罗斯男孩通过青春期和成年的人群进行前瞻性的跟进。这些男孩居住在俄罗斯的查普萨夫（Chapaevsk），这是一个工业小镇，记录了二恶英，弗拉斯（Furans），PCB和铅的高度接触。具体的目的是研究二恶英，呋喃，PCB和铅的聚伯伯伯伯伯伯果5血清浓度的关系：1）男性青春期发育的进展以及达成性成熟时的年龄（通过睾丸体积和坦纳阶段来衡量）； 2）体细胞生长，特别是高度，高度速度，体重增加和BMI； 3）调节体细胞生长和青春期发育的激素的血清浓度改变（睾丸激素，抑制蛋白B，MIS，LH，FSH，FSH，IGF-1，IGF-BP3，IGF-BP3，TSH和FREE TSH）； 4）成人睾丸功能的改变，特别是成熟睾丸功能的精液质量和激素标记和生殖轴（睾丸激素，抑制素-B，LH和FSH）。拟议的研究具有创新性，因为它代表了对环境对男性青春期发展，生长和生殖功能的影响的少数大型前瞻性队列研究之一。青春期和增长时间的改变已显示出不利的公共卫生和临床意义。例如，青春期的变化会对青春期的身体和性成熟，社交，认知和行为发展以及随后的成人肥胖和代谢障碍的风险产生不利影响。此外，在男性青春期发育的敏感窗口中，暴露于环境化学物质可能会通过亲子介导的作用对生育能力和下一代产生不利影响。因此，鉴定潜在可补救的危险因素，例如暴露于二恶英，Furans，PCB和铅，对于促进我们对环境对儿童健康影响的理解以及保护儿童健康和后代的理解至关重要。