Reproductive hormone profile and pubertal development in 14-year-old boys prenatally exposed to polychlorinated biphenyls

Philippe Grandjean,Ciea Grønlund,Ina M Kjær,Tina Kold Jensen,Nicolina Sørensen,Anna-Maria Andersson,Anders Juul,Niels E Skakkebæk,Esben Budtz-Jørgensen,Pal Weihe

doi:10.1016/j.reprotox.2012.07.005

Abstract

Because polychlorinated biphenyls (PCBs) are thought to cause endocrine disruption, we examined 438 adolescent boys from a birth cohort in the Faroe Islands, where PCB exposures are elevated. We measured PCBs and p,p′-dichlorodiphenyldichloroethylene (DDE) in cord blood and in serum from clinical examination at age 14. Higher prenatal PCB exposure was associated with lower serum concentrations of both luteinizing hormone (LH) and testosterone. In addition, sex hormone binding globulin (SHBG) was positively associated with both prenatal and concurrent PCB exposures. The PCB–SHBG association was robust to covariate adjustment. In a structural equation model, a doubling in prenatal PCB exposure was associated with a decrease in LH of 6% (p=0.03). Prenatal exposure to PCB and DDE showed weak, non-significant inverse associations with testicular size and Tanner stage. DDE was highly correlated with PCB and showed slightly weaker associations with the hormone profile. These findings suggest that delayed puberty with low serum-LH concentrations associated with developmental exposure to non dioxin-like PCBs may be due to a central hypothalamo-pituitary mechanism.

Highlights

Developmental exposure to polychlorinated biphenyls (PCBs) and related persistent pollutants may cause testicular dysfunction in humans [1]
Increased prenatal exposures determined from cord blood concentrations of PCBs and DDE were associated with slightly delayed puberty in the boys and an altered profile of serum concentrations of reproductive hormones at clinical follow-up at age 14 years
The lower serum concentrations of T and luteinizing hormone (LH), and the higher sex hormone binding globulin (SHBG) suggest that endocrine disruption due to developmental PCB exposure could be mediated via toxicity to the central part of the hypothalamo-pituitary-gonadal axis, perhaps linked to central nervous system toxicity, as demonstrated in experimental studies [6, 7]

Summary

Introduction

Developmental exposure to polychlorinated biphenyls (PCBs) and related persistent pollutants may cause testicular dysfunction in humans [1]. PCB congeners are known to cause both neurotoxicity [2, 3] and endocrine disruption [4], the latter supported by experimental demonstration of adverse effects on both testicular cells [5] and the hypothalamus [6, 7]. PCBs may potentially exert adverse effects by affecting different aspects of the hypothalamic-pituitary-gonadal axis [4, 7]. Human PCB exposure involves other persistent and lipophilic chemicals, such as p,p′dichlorodiphenyltrichloroethane (DDT) and its more persistent metabolite p,p′dichlorodiphenyldichloroethylene (DDE), both of which have been implicated as endocrine disruptors [4, 10].

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