Effects of Environmental Phthalates and Chemical Mixtures on Male Puberty and Semen Quality

环境邻苯二甲酸盐和化学混合物对男性青春期和精液质量的影响

• 批准号: 9235841
• 负责人: RUSS B HAUSER
• 金额: $ 61.48万
• 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 2021-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9235841
• 关键词: Adult; Adverse effects; Age; Archives; Behavioral; Chemicals; Chlorinated Hydrocarbons; Cognitive; Data; Development; Dioxins; Energy Intake; Enrollment; Environmental Impact; Environmental Risk Factor; Exposure to; Funding; Furans; Growth; Hormonal Change; Impairment; Individual; Infertility; Joints; Lead; Life; Longitudinal Studies; Longitudinal cohort study; Luteinizing Hormone; Measures; Metabolic; Metals; Obesity; Outcome; Parents; Pesticides; Polychlorinated Biphenyls; Prospective Studies; Prospective cohort study; Puberty; Public Health; Reporting; Reproductive Health; Risk; Risk Factors; Rodent; Rodent Model; Sampling; Seminal fluid; Serum; Social Functioning; Sperm Count Procedure; Sperm Motility; Testosterone; Time trend; Urine; Visit; androgenic; base; boys; cohort; consumer product; cost effective; early onset; environmental chemical; experimental study; exposed human population; follow-up; girls; male; modifiable risk; novel; organochlorine pesticide; phthalates; prepuberty; prospective; reproductive; reproductive axis; reproductive development; reproductive hormone; sperm cell; sperm morphology; toxicant; urinary

ABSTRACT The pubertal transition from pre-puberty to sexual maturity entails dynamic physical, behavioral, and hormonal changes. Although studies report temporal trends towards an earlier onset of puberty in girls, there are limited data in boys on temporal trends of pubertal onset. Moreover, there is a dearth of longitudinal studies on the impact of environmental chemicals on male puberty. Phthalates are one class of chemicals for which there is scientific and regulatory concern regarding their potential effects on male pubertal development and testicular function. This concern is based upon numerous experimental studies in rodents showing that some phthalates are anti-androgenic and are male developmental and reproductive toxicants, causing delayed pubertal onset, decreased serum testosterone concentrations and impaired semen quality. Based on the experimental data and the documented widespread human exposure to phthalates, in this competing renewal we propose to investigate the effect of phthalates (individual phthalates and their mixtures) on male pubertal development, reproductive hormones and semen quality. We will leverage our unique well-defined longitudinal cohort study of 499 Russian boys followed from enrollment at age 8 until 21 years. Our pilot data on a small subset of the cohort shows high urinary concentrations of multiple anti-androgenic phthalate metabolites. In the competing renewal, we will measure urinary concentrations of phthalate metabolites in archived urine samples collected annually during twelve years of follow-up. To evaluate the effect of phthalate exposure during three sensitive windows, we will pool annual urine samples for each boy as follows: 1) pre-pubertal window (pool all samples collected at annual visits when testicular volume <4 ml), 2) early through mid-pubertal window (pool all samples collected at annual visits when testicular volume is between 4 and less than 15 ml), and 3) late-pubertal window (pool all samples collected at annual visits when testicular volume is 15 ml or greater). Our study will be one of the first prospective cohort studies in boys that will assess the effect of phthalate exposure at three sensitive windows on puberty and semen quality. We also have the unique opportunity to investigate the effect of exposure to real-life mixtures of phthalates and environmental chemicals/metals (organochlorines, including dioxins, furans, PCBs, pesticides and lead were measured in our current funding period) on puberty and semen quality. Altered timing and progression of puberty are an important public health issue because they may have adverse effects on growth, social functioning, cognitive and behavioral development, and adult metabolic and reproductive health. Furthermore, poor semen quality increases risk of infertility. In conclusion, elucidating the association of prevalent environmental chemicals with adverse male reproductive development may reveal potentially modifiable risk factors (for example, reducing phthalate use in consumer products).

摘要 从青春期前期到性成熟的青春期过渡需要动态的身体、行为和心理健康。 荷尔蒙变化虽然研究报告了女孩青春期提前的时间趋势， 关于男孩青春期开始时间趋势的数据有限。此外，缺乏 关于环境化学品对男性青春期影响的纵向研究。邻苯二甲酸酯是一类 在科学和监管方面存在对男性潜在影响的化学品 青春期发育和睾丸功能。这种担忧是基于许多实验研究， 啮齿类动物显示，一些邻苯二甲酸酯是抗雄激素和男性发育和生殖 有毒物质，造成青春期延迟，降低血清睾酮浓度， 精液质量根据实验数据和记录的人类广泛接触 邻苯二甲酸酯，在这个竞争性的更新，我们建议调查邻苯二甲酸酯的影响（个人） 邻苯二甲酸酯及其混合物）对男性青春期发育、生殖激素和精液质量的影响。 我们将利用我们独特的定义明确的纵向队列研究，对499名俄罗斯男孩进行随访， 8岁至21岁入学。我们对一小部分队列的初步数据显示， 多种抗雄激素邻苯二甲酸酯代谢物的浓度。在竞争性更新中，我们将衡量 12年期间每年收集的存档尿样中邻苯二甲酸酯代谢物的尿液浓度 多年的后续。为了评估三个敏感窗口期间邻苯二甲酸酯暴露的影响，我们将 每个男孩的年度尿液样本如下：1）青春期前窗口（合并每年收集的所有样本 睾丸体积<4 ml时的访视），2）早期至青春期中期窗口（合并所有在 当睾丸体积在4和小于15 ml之间时，每年进行一次访视），和3）青春期晚期窗口（汇总所有 当睾丸体积为15 ml或更大时，在年度访视时采集样本）。我们的研究将是 在男孩中进行的第一项前瞻性队列研究，将评估邻苯二甲酸酯暴露对三个敏感水平的影响。 青春期和精液质量的窗口。我们也有独特的机会来研究 接触邻苯二甲酸盐和环境化学品/金属（有机氯，包括 二恶英、呋喃、多氯联苯、杀虫剂和铅在我们目前的资助期内进行了测量）， 精液质量青春期的时间和进展的改变是一个重要的公共卫生问题，因为它们 可能对生长、社会功能、认知和行为发育以及成年 代谢和生殖健康。此外，精液质量差会增加不育的风险。在 结论，阐明了普遍存在的环境化学物质与不良男性行为的关系， 生殖发育可能揭示潜在的可改变的风险因素（例如，减少邻苯二甲酸酯 用于消费品）。