TY - JOUR

T1 - Association between chemical pattern in breast milk and congenital cryptorchidism

T2 - modelling of complex human exposures

AU - Krysiak-Baltyn, Konrad

AU - Toppari, J

AU - Skakkebaek, N E

AU - Jensen, T S

AU - Virtanen, H E

AU - Schramm, K-W

AU - Shen, Hao

AU - Vartiainen, T

AU - Kiviranta, H

AU - Taboureau, Olivier

AU - Audouze, Karine Marie Laure

AU - Brunak, Søren

AU - Main, K M

N1 - © 2012 The Authors. International Journal of Andrology © 2012 European Academy of Andrology.

PY - 2012

Y1 - 2012

N2 - During the past four decades, there has been an increase in the incidence rate of male reproductive disorders in some, but not all, Western countries. The observed increase in the prevalence of male reproductive disorders is suspected to be ascribable to environmental factors as the increase has been too rapid to be explained by genetics alone. To study the association between complex chemical exposures of humans and congenital cryptorchidism, the most common malformation of the male genitalia, we measured 121 environmental chemicals with suspected or known endocrine disrupting properties in 130 breast milk samples from Danish and Finnish mothers. Half the newborns were healthy controls, whereas the other half was boys with congenital cryptorchidism. The measured chemicals included polychlorinated biphenyls (PCBs), polybrominated diphenyl-ethers, dioxins (OCDD/PCDFs), phthalates, polybrominated biphenyls and organochlorine pesticides. Computational analysis of the data was performed using logistic regression and three multivariate machine learning classifiers. Furthermore, we performed systems biology analysis to explore the chemical influence on a molecular level. After correction for multiple testing, exposure to nine chemicals was significantly different between the cases and controls in the Danish cohort, but not in the Finnish cohort. The multivariate analysis indicated that Danish samples exhibited a stronger correlation between chemical exposure patterns in breast milk and cryptorchidism than Finnish samples. Moreover, PCBs were indicated as having a protective effect within the Danish cohort, which was supported by molecular data recovered through systems biology. Our results lend further support to the hypothesis that the mixture of environmental chemicals may contribute to observed adverse trends in male reproductive health.

AB - During the past four decades, there has been an increase in the incidence rate of male reproductive disorders in some, but not all, Western countries. The observed increase in the prevalence of male reproductive disorders is suspected to be ascribable to environmental factors as the increase has been too rapid to be explained by genetics alone. To study the association between complex chemical exposures of humans and congenital cryptorchidism, the most common malformation of the male genitalia, we measured 121 environmental chemicals with suspected or known endocrine disrupting properties in 130 breast milk samples from Danish and Finnish mothers. Half the newborns were healthy controls, whereas the other half was boys with congenital cryptorchidism. The measured chemicals included polychlorinated biphenyls (PCBs), polybrominated diphenyl-ethers, dioxins (OCDD/PCDFs), phthalates, polybrominated biphenyls and organochlorine pesticides. Computational analysis of the data was performed using logistic regression and three multivariate machine learning classifiers. Furthermore, we performed systems biology analysis to explore the chemical influence on a molecular level. After correction for multiple testing, exposure to nine chemicals was significantly different between the cases and controls in the Danish cohort, but not in the Finnish cohort. The multivariate analysis indicated that Danish samples exhibited a stronger correlation between chemical exposure patterns in breast milk and cryptorchidism than Finnish samples. Moreover, PCBs were indicated as having a protective effect within the Danish cohort, which was supported by molecular data recovered through systems biology. Our results lend further support to the hypothesis that the mixture of environmental chemicals may contribute to observed adverse trends in male reproductive health.

U2 - 10.1111/j.1365-2605.2012.01268.x

DO - 10.1111/j.1365-2605.2012.01268.x

M3 - Journal article

C2 - 22519522

VL - 35

SP - 294

EP - 302

JO - International Journal of Andrology

JF - International Journal of Andrology

SN - 0105-6263

IS - 3

ER -