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.

Human environmental disease network: A computational model to assess toxicology of contaminants

“…In our network, HCB is predicted to be associated with reproductive disorders such as congenital malformation and abnormal sperm. Environmental exposure to endocrine disrupting chemicals, including HCB, have been suggested as a risk factor for male genital abnormalities such as hypospadias (Rignell-Hydbom et al, 2012;Krysiak-Baltyn et al, 2012). A recent study showed for the first time a correlation between serum concentration of HCB and semen quality (Paoli et al, 2015).…”

Addressing the temporal fit of institutions: the regulation of endocrine-disrupting chemicals in Europe

“…Although the research is highly uncertain, there are strong indications that similar patterns of critical temporal vulnerabilities are present in all "wildlife" categories addressed by Kortenkamp et al (2011), i.e., other mammals, birds, fish, and invertebrates. In addition, EDC scientists as well as researchers developing new technologies for the monitoring and assessment of hormonally active substances have identified serious environmental consequences from releasing them into the environment (Hyötyläinen and Riekkola 2007, Kortenkamp et al 2011, Krysiak-Baltyn et al 2012. Finally, recent research on EDCs has demonstrated that geographical differences matter.…”

“…Finally, recent research on EDCs has demonstrated that geographical differences matter. Whether or not adverse effects will occur depends not only on the specific compounds found in a particular area, but on the specific mixtures these compounds happen to form as a result of agriculture, industry, and consumption patterns (Krysiak-Baltyn et al 2012).…”

Exposure Variation and Endocrine Disruption of the Male Reproductive System

“…To test the hypothesis, we measured more than one hundred toxicants in placentas and breast milk of mothers of boys with and without cryptorchidism in both Denmark and Finland to estimate the amount of prenatal exposure to endocrine disruptors [14,15,16,17,18,19], including 17 dioxin, 37 PCB, and 14 PBDE congeners. Dioxins, and dioxin-like PCBs, are well-known toxicants that exert most of their endocrine effects through aryl hydrocarbon receptors (AhR) that may interact with many other transcription factors [20].…”

“…Although the PCBs have not been produced in large scale after the 1980s [1] and the production and circulation of PCBs, dioxins, and most PBDE congeners was planned to be stopped under the Stockholm Convention [23] due to their chemical properties, they are still present in fauna even in remote locations such as Svalbard in the Arctic Ocean [24]. In the Danish-Finnish birth cohort study, exposures were measured in breast milk collected over a 2-month period starting at 1 month after delivery [14,17,25]. After each feeding when the baby was satisfied, the mother collected some of the remaining milk in a cup that was emptied in a glass bottle that was stored in the freezer.…”