Prenatal and Early Life Exposure to Polychlorinated Dibenzo-p-Dioxins, Dibenzofurans and Biphenyls May Influence Dehydroepiandrosterone Sulfate Levels at Prepubertal Age: Results from the Duisburg Birth Cohort Study

Polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/F) and polychlorinated biphenyls (PCB) are postulated to act as endocrine disrupters. In the ongoing Duisburg birth cohort study, started in 2000–2002, influence of persistent organic pollutants (POP) on child development was monitored. For the first time, associations were reported between prenatal and postnatal PCDD/F and PCB exposures and early endocrinological changes concerning adrenarchal development. PCDD/F and PCB concentrations were measured in blood samples taken in wk 32 of pregnancy and in breast milk using gas chromatography and high-resolution mass spectrometry (GC/HRMS). At the age of 6–7 and 8–9 yr, serum samples were collected from 111 children. The samples were assayed for the sex hormones testosterone, estradiol, dehydroepiandrosterone sulfate (DHEA-S), and 17-OH-progesterone (17-OHP) by using an automated chemiluminescence assay system. Analyses of repeated measurements of DHEA-S serum levels were performed by linear regression analysis using generalized estimating equations (GEE). Linear regression analysis showed a positive association between DHEA-S and breast milk levels of PCDD/F and PCB expressed as toxicity equivalents according to toxicity equivalent factors published by the World Health Organization (WHO) in 2005 (WHO2005-TEq) (increase of 29%, geometric mean ratio, GMR: 1.29, 95% CI 1.06–1. 58 per doubling of PCDD/F + PCB WHO2005-TEq levels). Results for the association with the WHO2005-TEq levels in blood of mothers were in the same direction (increase of 15%, GMR 1.15, 95% CI 0.93–1.42 per doubling of PCDD/F + PCB WHO2005-TEq levels), but not significant. Data indicate that PCDD/F and PCB exposure in infancy may influence DHEA-S serum levels in prepubertal children. Increased DHEA-S serum levels are considered to indicate acceleration of the adrenal maturation.

[1]  D. Dunger,et al.  Higher Levels of IGF-I and Adrenal Androgens at Age 8 Years Are Associated with Earlier Age at Menarche in Girls , 2012, The Journal of clinical endocrinology and metabolism.

[2]  J..  Skinfold Equations for Estimation of Body Fatness in Children and Youth I , 2012 .

[3]  R. Auchus.  The physiology and biochemistry of adrenarche. , 2011, Endocrine development.

[4]  J. Toppari,et al.  Trends in puberty timing in humans and environmental modifiers , 2010, Molecular and Cellular Endocrinology.

[5]  J. Bourguignon,et al.  Neuroendocrine disruption of pubertal timing and interactions between homeostasis of reproduction and energy balance , 2010, Molecular and Cellular Endocrinology.

[6]  J. Bourguignon,et al.  Early homeostatic disturbances of human growth and maturation by endocrine disrupters , 2010, Current opinion in pediatrics.

[7]  T. Remer,et al.  Prepubertal adrenarchal androgens and animal protein intake independently and differentially influence pubertal timing. , 2010, The Journal of clinical endocrinology and metabolism.

[8]  H. Leffers,et al.  Hypothesis: exposure to endocrine-disrupting chemicals may interfere with timing of puberty. , 2010, International journal of andrology.

[9]  Takashi Suzuki,et al.  Development of the human adrenal zona reticularis: morphometric and immunohistochemical studies from birth to adolescence. , 2009, The Journal of endocrinology.

[10]  Takashi Suzuki,et al.  Adrenal changes associated with adrenarche , 2009, Reviews in Endocrine and Metabolic Disorders.

[11]  E. Ullerås,et al.  Secretion of cortisol and aldosterone as a vulnerable target for adrenal endocrine disruption — screening of 30 selected chemicals in the human H295R cell model , 2008, Journal of applied toxicology : JAT.

[12]  Signe E. Larson,et al.  Environmental exposures and puberty in inner-city girls. , 2008, Environmental research.

[13]  M. Wilhelm,et al.  The Duisburg birth cohort study: influence of the prenatal exposure to PCDD/Fs and dioxin-like PCBs on thyroid hormone status in newborns and neurodevelopment of infants until the age of 24 months. , 2008, Mutation research.

[14]  M. Wilhelm,et al.  Lack of Neurodevelopmental Adversity by Prenatal Exposure of Infants to Current Lowered PCB Levels: Comparison of Two German Birth Cohort Studies , 2008, Journal of toxicology and environmental health. Part A.

[15]  M. Wilhelm,et al.  Environmental exposure to dioxins and polychlorinated biphenyls reduce levels of gonadal hormones in newborns: results from the Duisburg cohort study. , 2008, International journal of hygiene and environmental health.

[16]  G. Schoeters,et al.  Endocrine disruptors and abnormalities of pubertal development. , 2008, Basic & clinical pharmacology & toxicology.

[17]  N. Skakkebaek,et al.  Role of Environmental Factors in the Timing of Puberty , 2008, Pediatrics.

[18]  E. Reiter.  When Puberty Is Precocious , 2007, Endocrine.

[19]  M. Wilhelm,et al.  PCDD/F and dioxin-like PCB in human blood and milk from German mothers. , 2007, Chemosphere.

[20]  J. T. Sanderson,et al.  The steroid hormone biosynthesis pathway as a target for endocrine-disrupting chemicals. , 2006, Toxicological sciences : an official journal of the Society of Toxicology.

[21]  B. Eskenazi,et al.  Serum dioxin concentrations and age at menarche. , 2004, Environmental health perspectives.

[22]  G. Lambert,et al.  Yucheng: health effects of prenatal exposure to polychlorinated biphenyls and dibenzofurans , 2004, International archives of occupational and environmental health.

[23]  J. Toppari,et al.  The timing of normal puberty and the age limits of sexual precocity: variations around the world, secular trends, and changes after migration. , 2003, Endocrine reviews.

[24]  P. Deurenberg.  Validation of body composition methods and assumptions , 2003, British Journal of Nutrition.

[25]  M. Elmlinger,et al.  Reference Ranges for Serum Concentrations of Lutropin (LH), Follitropin (FSH), Estradiol (E2), Prolactin, Progesterone, Sex Hormone-Binding Globulin (SHBG), Dehydroepiandrosterone Sulfate (DHEAS), Cortisol and Ferritin in Neonates, Children and Young Adults , 2002, Clinical chemistry and laboratory medicine.

[26]  M Porta,et al.  Implementing the Stockholm Treaty on Persistent Organic Pollutants , 2002, Occupational and environmental medicine.

[27]  Jan A Staessen,et al.  Sexual maturation in relation to polychlorinated aromatic hydrocarbons: Sharpe and Skakkebaek's hypothesis revisited. , 2002, Environmental health perspectives.

[28]  W. Crowley,et al.  The longitudinal study of adrenal maturation during gonadal suppression: evidence that adrenarche is a gradual process. , 2001, The Journal of clinical endocrinology and metabolism.

[29]  E. P. Dekoning,et al.  PCB exposure in utero and via breast milk. A review , 2000, Journal of Exposure Analysis and Environmental Epidemiology.

[30]  B. Gladen,et al.  Pubertal growth and development and prenatal and lactational exposure to polychlorinated biphenyls and dichlorodiphenyl dichloroethene. , 2000, The Journal of pediatrics.

[31]  L. Parker.  Control of adrenal androgen secretion. , 1991, Endocrinology and metabolism clinics of North America.

[32]  R A Boileau,et al.  Skinfold equations for estimation of body fatness in children and youth. , 1988, Human biology.

[33]  C. Kelnar,et al.  A MIXED LONGITUDINAL STUDY OF ADRENAL STEROID EXCRETION IN CHILDHOOD AND THE MECHANISM OF ADRENARCHE , 1983 .

[34]  J. Winter,et al.  Further studies on adrenarche in nonhuman primates. , 1982, Endocrinology.