ИСТИНА

Предварительно собранные данные из продольной когорты российских мальчиков (от 8 до 21 года) будут использованы для оценки влияния фталатов на развитие в подростковом возрасте, концентрации репродуктивных гормонов в сыворотке и качество семени. Будет оценено влияние временного интервала внешнего воздействия, например, в предпубертатном, среднепубертатном и позднепубертатном возрасте, на связь между фталатами и возрастными и репродуктивными изменениями. Для проведения этих исследований важное значение имеет измерение фталатов в собранных образцах мочи этих российских участников. Методы измерения фталатов в образцах мочи будут внедрены в химической лаборатории Московского государственного университета. Основной российский исследователь, Олег Сергеев, является сотрудником Научно-исследовательского института физико-химической биологии имени А.Н. Белозерского МГУ, основного места научной координации проекта. В лаборатории будут проанализированы не менее 1500 собранных образцов мочи, а также проведен дополнительный анализ образцов для процедуры контроля качества. В лаборатории будет разработана информационная база данных по результатам анализов образцов мочи на фталаты. В МГУ будет обеспечено долгосрочное хранение образцов мочи, а также конфиденциальной информации. Вслед за этим последует статистический анализ данных, подготовка рукописи и публикация в рецензируемых журналах.

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 20 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 remediable risk factors (for example, reducing phthalate use in consumer products).

Prospectively collected data from a longitudinal cohort of Russian boys (from ages 8 to 21 years) will be utilized to assess the effects of phthalates on pubertal development, serum concentrations of reproductive hormones, and semen quality. We will assess whether the timing of exposure, e.g. pre-pubertal, early through mid-pubertal, and late-pubertal, is an important factor in the associations between phthalates and these pubertal and reproductive outcomes. In order to carry out these investigations, it is crucial to measure phthalates in the collected urine samples of these Russian participants. We will implement methods of phthalate measurements in urine samples at the chemical laboratory of Moscow State University. The Russian Principal Researcher, Oleg Sergeyev is also affiliated with the A.N. Belozersky Research Institute Of Physico-Chemical Biology, Moscow State University, that would be primary site for academic project management. Laboratory will analyze at least 1500 pooled urine samples with additional analysis of samples for QC\QA. Informational database with results of analysis of urine samples for phthalates will be developed at laboratory. The long-term storage of urine samples and confidential information in Moscow State University will be provided. Statistical analysis, manuscript preparation and publication in peer reviewed journals will be followed.