No association between exposure to perfluorinated compounds and congenital cryptorchidism: a nested case–control study among 215 boys from Denmark and Finland

Abstract

Geographical differences in the occurrence of diseases in male reproductive organs, including malformation in reproductive tract, between Denmark and Finland have been reported. The reason for these differences is unknown, but differences in exposure to chemicals with endocrine-disrupting abilities have been suggested. Among these chemicals are perfluoro-alkylated substances (PFASs), a group of water-and grease-repellent chemicals used in outdoor clothes, cookware, food packaging, and textiles. In this study, we, therefore, investigated differences in PFAS exposure levels between Denmark and Finland and the association between cord blood PFAS levels and congenital cryptorchidism. Boys from a joint ongoing prospective birth cohort study were included. We analyzed PFAS levels in cord blood serum samples collected from 29 Danish boys with congenital cryptorchidism, 30 healthy Danish matched controls recruited from 1997 to 2001, 30 Finnish cases, and 78 Finnish healthy matched controls recruited from 1997 to 1999. Additionally, 48 Finnish cases recruited from 2000 to 2002 were included. Perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS) were detected in all the 215 Danish and Finnish cord blood samples with significantly higher levels being observed in the Danish samples (medians: PFOA, 2.6 ng/ml and PFOS, 9.1 ng/ml) than in the Finnish samples (medians: PFOA, 2.1 ng/ml and PFOS, 5.2 ng/ml). We found no associations between cord blood PFOA and PFOS levels and congenital cryptorchidism after adjustment for confounders. Our data indicate that women in Denmark and Finland are generally exposed to PFOA and PFOS but there are differences in exposure levels between countries. We found no statistically significant association between cord blood PFOA and PFOS levels and congenital cryptorchidism; however, our study was small and larger studies are warranted.

Perfluorooctane Sulfonate Concentrations in Amniotic Fluid, Biomarkers of Fetal Leydig Cell Function, and Cryptorchidism and Hypospadias in Danish Boys (1980–1996)

“…Evidence of effects on fetal Leydig cell hormone production has led others to hypothesize that PFOS exposure might affect androgen- and insulin-like factor 3 (INSL3)–dependent testicular descent ( Bay et al 2011 ) and scrotal fusion ( Kalfa et al 2009 ). Only one previous study has evaluated the risk of cryptorchidism in relation to PFAS exposure; this study did not observe associations between PFAS level in cord blood and cryptorchidism ( Vesterholm et al 2014 ). However, due to a limited study size of 59 cryptorchidism cases and 108 matched controls, the power to show an association was limited.…”

The epidemiologic evidence linking prenatal and postnatal exposure to endocrine disrupting chemicals with male reproductive disorders: a systematic review and meta-analysis

“…We identified 33 papers that were based upon 28 independent studies reported 89 associations between measured levels of endocrine disrupting chemicals and one or more of the outcomes: cryptorchidism (Hosie et al ., 2000; Longnecker et al ., 2002; Pierik et al ., 2004, 2007; Bhatia et al ., 2005; Damgaard et al ., 2006; Main et al ., 2007; Brucker-Davis et al ., 2008; McGlynn et al ., 2009a; Fenichel et al ., 2012; Chevalier et al ., 2015; Jensen et al ., 2015; Komarowska et al ., 2015; Small et al ., 2009; Trabert et al ., 2012; Vesterholm et al ., 2014; Toft et al ., 2016; Virtanen et al ., 2012); hypospadias (Longnecker et al ., 2002; Bhatia et al ., 2005; Small et al ., 2009; McGlynn et al ., 2009a; Carmichael et al ., 2010; Giordano et al ., 2010; Choi et al ., 2012; Jensen et al ., 2015; Rignell-Hydbom et al ., 2012; Trabert et al ., 2012; Toft et al ., 2016); testicular cancer (Hardell et al ., 2003, 2004; Biggs et al ., 2008; Cohn et al ., 2010; Giannandrea et al ., 2011; McGlynn et al ., 2008; 2009b; Purdue et al ., 2009); and sperm count (Mocarelli et al ., 2011; Axelsson et al ., 2015; Vested et al ., 2013, 2014). …”

Risk factors for cryptorchidism

“…Some authors have observed higher levels of the compounds bisphenol A , 176 dibutylin 169 dioxin , 164,173 heptachloroepoxide , 174 hexachlorobenzene , 174 polychlorinated biphenyls 164,173,177 and polybrominateddiphenyl ethers 159,164 among boys (and/or their mothers) who developed cryptorchidism compared to those who did not; however a substantial number of studies (at least some of which were adequately powered to detect an association) have directly evaluated these and other biologically-plausible compounds and found no such association. 56,60,152–157,160,163,168,172,178 In some cases, studies have found substantial regional heterogeneity, including conflicting results between countries within the same study. 161,162,164,169 For example, Rantakokko et al 169 observed that maternal exposure to high levels (>0.15ng/g) of dibutylin was associated with increased risk of cryptorchidism in Danish sons (adjusted OR vs. <0.10ng/g: 4.01, 95% CI 1.42–11.33), but was inversely associated in Finnish sons (adjusted OR: 0.16, 95% CI 0.03–0.75).…”

“…Maternal or childhood direct exposure to endocrine-disrupting chemicals 56,60,152–157,159,160,163,164,168,169,172–174,176–178 …”