title: Association between chemical pattern in breast milk and congenital cryptorchidism: modelling of complex human exposures.
abstract: 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.
authors.affiliation: Center for Biological Sequence Analysis, Technical University of Denmark, Lyngby, Denmark.
authors.forename: K
authors.initials: K
authors.lastname: Krysiak-Baltyn
authors.forename: J
authors.initials: J
authors.lastname: Toppari
authors.forename: N E
authors.initials: NE
authors.lastname: Skakkebaek
authors.forename: T S
authors.initials: TS
authors.lastname: Jensen
authors.forename: H E
authors.initials: HE
authors.lastname: Virtanen
authors.forename: K-W
authors.initials: KW
authors.lastname: Schramm
authors.forename: H
authors.initials: H
authors.lastname: Shen
authors.forename: T
authors.initials: T
authors.lastname: Vartiainen
authors.forename: H
authors.initials: H
authors.lastname: Kiviranta
authors.forename: O
authors.initials: O
authors.lastname: Taboureau
authors.forename: K
authors.initials: K
authors.lastname: Audouze
authors.forename: S
authors.initials: S
authors.lastname: Brunak
authors.forename: K M
authors.initials: KM
authors.lastname: Main
mesh_terms: D001185:Artificial Intelligence; D003456:Cryptorchidism / Q000453:epidemiology*; D003718:Denmark / Q000453:epidemiology; D004147:Dioxins / Q000032:analysis; D004785:Environmental Pollutants / Q000032:analysis; D005260:Female; D005387:Finland / Q000453:epidemiology; D055768:Halogenated Diphenyl Ethers / Q000032:analysis; D006801:Humans; D016015:Logistic Models; D008297:Male; D008895:Milk, Human / Q000737:chemistry*; D011078:Polychlorinated Biphenyls / Q000032:analysis; D049490:Systems Biology
chemical_list: D004147:Dioxins; D004785:Environmental Pollutants; D055768:Halogenated Diphenyl Ethers; D011078:Polychlorinated Biphenyls