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Christine Wohlfahrt-Veje, Karine Audouze, Søren Brunak, Jean Philippe Antignac, Bruno le Bizec, Anders Juul, Niels E Skakkebæk and Katharina Maria Main

Experimental studies have shown that dioxin-like chemicals may interfere with aspects of the endocrine system including growth. However, human background population studies are, however, scarce. We aimed to investigate whether early exposure of healthy infants to dioxin-like chemicals was associated with changes in early childhood growth and serum IGF1. In 418 maternal breast milk samples of Danish children (born 1997–2001) from a longitudinal cohort, we measured polychlorinated dibenzo-p-dioxins, polychlorinated dibenzofurans, and polychlorinated biphenyls (pg or ng/g lipid) and calculated total toxic equivalent (total TEQ). SDS and SDS changes over time (ΔSDS) were calculated for height, weight, BMI, and skinfold fat percentage at 0, 3, 18, and 36 months of age. Serum IGF1 was measured at 3 months. We adjusted for confounders using multivariate regression analysis. Estimates (in parentheses) correspond to a fivefold increase in total TEQ. TEQ levels in breast milk increased significantly with maternal age and fish consumption and decreased with maternal birth year, parity, and smoking. Total TEQ was associated with lower fat percentage (−0.45 s.d., CI: −0.89; −0.04), non-significantly with lower weight and length at 0 months, accelerated early height growth (increased ΔSDS) (ΔSDS 0–18 months: +0.77 s.d., CI: 0.34; 1.19) and early weight increase (ΔSDS 0–18: +0.52 s.d., CI: 0.03; 1.00), and increased IGF1 serum levels at 3 months (+13.9 ng/ml, CI: 2.3; 25.5). Environmental exposure to dioxin-like chemicals was associated with being skinny at birth and with higher infant levels of circulating IGF1 as well as accelerated early childhood growth (rapid catch-up growth).

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Hanne Frederiksen, Tina Kold Jensen, Niels Jørgensen, Henriette Boye Kyhl, Steffen Husby, Niels E Skakkebæk, Katharina M Main, Anders Juul and Anna-Maria Andersson

Several non-persistent industrial chemicals have shown endocrine disrupting effects in animal studies and are suspected to be involved in human reproductive disorders. Among the non-persistent chemicals that have been discussed intensively during the past years are phthalates, bisphenol A (BPA), triclosan (TCS), and parabens because of their anti-androgenic and/or estrogenic effects. Phthalates are plasticizers used in numerous industrial products. Bisphenol A is the main component of polycarbonate plastics and epoxy resins. Parabens and TCS are antimicrobial preservatives and other phenols such as benzophenone-3 (BP-3) act as a UV-screener, while chlorophenols and phenyl phenols are used as pesticides and fungicides in agriculture. In spite of the widespread use of industrial chemicals, knowledge of exposure sources and human biomonitoring studies among different segments of the population is very limited. In Denmark, we have no survey programs for non-persistent environmental chemicals, unlike some countries such as the USA (NHANES) and Germany (GerES). However, we have analyzed the excretion of seven parabens, nine phenols, and the metabolites of eight different phthalates in urine samples collected over the past 6 years from four Danish cohorts. Here, we present biomonitoring data on more than 3600 Danish children, adolescents, young men, and pregnant women from the general population. Our study shows that nearly all Danes were exposed to the six most common phthalates, to BPA, TCS, and BP-3, and to at least two of the parabens. The exposure to other non-persistent chemicals was also widespread. Our data indicate decreasing excretion of two common phthalates (di-n-butyl phthalate and di-(2-ethylhexyl) phthalate) over time.

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Marie Lindhardt Johansen, Ravinder Anand-Ivell, Annette Mouritsen, Casper P Hagen, Mikkel G Mieritz, Tue Søeborg, Trine Holm Johannsen, Katharina M Main, Anna-Maria Andersson, Richard Ivell and Anders Juul

Insulin-like factor 3 (INSL3) is a promising marker of Leydig cell function with potentially high clinical relevance. Limited data of INSL3 levels in relation to other reproductive hormones in healthy pubertal boys exist. In this study, we aimed to evaluate longitudinal serum changes in INSL3 compared with LH, FSH, testosterone, inhibin B, and anti-Müllerian hormone (AMH) during puberty in healthy boys. Ten boys were included from the longitudinal part of the COPENHAGEN Puberty Study. Pubertal evaluation, including testicular volume, was performed and blood samples were drawn every 6 months for 5 years. Serum concentrations of testosterone were determined by a newly developed LC–MS/MS method, and serum concentrations of INSL3, AMH, inhibin B, FSH, and LH respectively were determined by validated immunoassays. The results showed that serum INSL3 levels increased progressively with increasing age, pubertal onset, and testicular volume. In six of the ten boys, LH increased before the first observed increase in INSL3. In the remaining four boys, the increase in LH and INSL3 was observed at the same examination. The increases in serum concentrations of LH, testosterone, and INSL3 were not parallel or in ordered succession and varied interindividually. We demonstrated that INSL3 concentrations were tightly associated with pubertal onset and increasing testicular volume. However, the pubertal increases in LH, INSL3, and testosterone concentrations were not entirely parallel, suggesting that INSL3 and testosterone may be regulated differently. Thus, we speculate that INSL3 provides additional information on Leydig cell differentiation and function during puberty compared with traditional markers of testicular function.