title: Association between levels of persistent organic pollutants in adipose tissue and cryptorchidism in early childhood: a case-control study.
abstract: BACKGROUND
  Congenital cryptorchidism, i.e. failure of the testicular descent to the bottom of the scrotum, is a common birth defect. The evidence from epidemiological, wildlife, and animal studies suggests that exposure to mixtures of endocrine disrupting chemicals during fetal development may play a role in its pathogenesis. We aimed to assess the association between cryptorchidism and prenatal exposure to polychlorinated biphenyls (PCBs), polychlorinated dibenzo-p-dioxins and furans (PCDD/Fs), and polybrominated diphenyl ethers (PBDEs).
  
  
  METHODS
  We conducted a case-control study consisting of 44 cryptorchid cases, and 38 controls operated for inguinal hernia, umbilical hernia, or hydrocele at the Turku University Hospital or Rigshospitalet, Copenhagen in 2002-2006. During the operation a subcutaneous adipose tissue biopsy was taken. Samples were analysed for 37 PCBs, 17 PCDD/Fs and 14 PBDEs by gas chromatography-high-resolution mass spectrometry. Chemical concentrations were adjusted for postnatal variation introduced by differences in duration of breastfeeding, age at the operation, and country of origin with a multiple linear regression. Association between adjusted and unadjusted chemical concentrations and the risk of cryptorchidism were analysed with logistic regression to get an estimate for odds ratio (OR) of cryptorchidism per multiplication of chemical concentrations with ca. 2.71 (Napier's constant).
  
  
  RESULTS
  Total-TEq i.e. the WHO-recommended 2,3,7,8-TCDD equivalent quantity of 17 dioxins and 12 dioxin-like PCBs and sum of PCDD/Fs were positively associated with cryptorchidism [OR 3.21 (95% CI 1.29-9.09), OR 3.69 (95% CI 1.45-10.9), respectively], when adjusting for country of origin, the duration the child was breastfed, and age at operation. The association between the sum of PCBs and cryptorchidism was close to significant [OR 1.92 (95% CI 0.98-4.01)], whereas the association between the sum of PBDEs and cryptorchidism was not [OR 0.86 (95% CI 0.47-1.54)]. There were no associations between unadjusted chemical concentrations and the risk of cryptorchidism.
  
  
  CONCLUSIONS
  Prenatal exposure to PCDD/Fs and PCDD/F-like PCBs may be associated with increased risk for cryptorchidism. Our finding does not exclude the possibility of an association between the exposure to PBDEs and cryptorchidism.
authors.affiliation: Departments of Physiology and Paediatrics, University of Turku and Turku University Hospital, Kiinamyllynkatu 10, FI-20520, Turku, Finland. jaakko.koskenniemi@utu.fi.|Department of Growth and Reproduction and EDMaRC, Rigshospitalet, Blegdamsvej 9, DK-2100, Copenhagen, Denmark. jaakko.koskenniemi@utu.fi.
authors.forename: Jaakko J
authors.initials: JJ
authors.lastname: Koskenniemi
authors.affiliation: Departments of Physiology and Paediatrics, University of Turku and Turku University Hospital, Kiinamyllynkatu 10, FI-20520, Turku, Finland. helena.virtanen@utu.fi.
authors.forename: Helena E
authors.initials: HE
authors.lastname: Virtanen
authors.affiliation: National Institute for Health and Welfare, Department of Health Protection, P.O. Box 95, FI-70701, Kuopio, Finland. hannu.kiviranta@thl.fi.
authors.forename: Hannu
authors.initials: H
authors.lastname: Kiviranta
authors.affiliation: Department of Growth and Reproduction and EDMaRC, Rigshospitalet, Blegdamsvej 9, DK-2100, Copenhagen, Denmark. ida@dadlnet.dk.
authors.forename: Ida N
authors.initials: IN
authors.lastname: Damgaard
authors.affiliation: Clinical Research Center, Turku University Hospital, Kiinamyllynkatu 4-8 PL 52, FI-20521, Turku, Finland. jaakko.matomaki@utu.fi.
authors.forename: Jaakko
authors.initials: J
authors.lastname: Matomäki
authors.affiliation: The Department of Paediatric Surgery, Rigshospitalet, Blegdamsvej 9, DK-2100, Copenhagen, Denmark. joergen.mogens.thorup@regionh.dk.|Faculty of Health and Medical Science, University of Copenhagen, Blegdamsvej 3B, DK-2200, Copenhagen, Denmark. joergen.mogens.thorup@regionh.dk.
authors.forename: Jørgen M
authors.initials: JM
authors.lastname: Thorup
authors.affiliation: Department of Paediatric Surgery, Turku University Hospital, Kiinamyllynkatu 4-8 PL 52, FI-20521, Turku, Finland. timhur@tyks.fi.
authors.forename: Timo
authors.initials: T
authors.lastname: Hurme
authors.affiliation: Department of Growth and Reproduction and EDMaRC, Rigshospitalet, Blegdamsvej 9, DK-2100, Copenhagen, Denmark. Niels.Erik.Skakkebaek@regionh.dk.|Faculty of Health and Medical Science, University of Copenhagen, Blegdamsvej 3B, DK-2200, Copenhagen, Denmark. Niels.Erik.Skakkebaek@regionh.dk.
authors.forename: Niels E
authors.initials: NE
authors.lastname: Skakkebaek
authors.affiliation: Department of Growth and Reproduction and EDMaRC, Rigshospitalet, Blegdamsvej 9, DK-2100, Copenhagen, Denmark. Katharina.Main@regionh.dk.|Faculty of Health and Medical Science, University of Copenhagen, Blegdamsvej 3B, DK-2200, Copenhagen, Denmark. Katharina.Main@regionh.dk.
authors.forename: Katharina M
authors.initials: KM
authors.lastname: Main
authors.affiliation: Departments of Physiology and Paediatrics, University of Turku and Turku University Hospital, Kiinamyllynkatu 10, FI-20520, Turku, Finland. jorma.toppari@utu.fi.
authors.forename: Jorma
authors.initials: J
authors.lastname: Toppari
mesh_terms: D000273:Adipose Tissue / Q000737:chemistry; D001572:Benzofurans / Q000633:toxicity; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D003430:Cross-Sectional Studies; D003456:Cryptorchidism / Q000139:chemically induced / Q000453:epidemiology*; D003718:Denmark / Q000453:epidemiology; D000072338:Dibenzofurans, Polychlorinated; D004147:Dioxins / Q000633:toxicity; D004785:Environmental Pollutants / Q000633:toxicity*; D005260:Female; D005387:Finland / Q000453:epidemiology; D055768:Halogenated Diphenyl Ethers / Q000633:toxicity; D006801:Humans; D015994:Incidence; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D011078:Polychlorinated Biphenyls / Q000633:toxicity; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced / Q000453:epidemiology*
chemical_list: D001572:Benzofurans; D000072338:Dibenzofurans, Polychlorinated; D004147:Dioxins; D004785:Environmental Pollutants; D055768:Halogenated Diphenyl Ethers; D011078:Polychlorinated Biphenyls