title: A novel biomarker for anti-androgenic activity in placenta reveals risks of urogenital malformations.
abstract: It has been hypothesized that the rise in male reproductive disorders over recent decades may at least be partially attributable to environmental factors, including chemical exposures, but observed associations with single chemicals were rather weak. The aim of this case-control study was to explore the relationship between exposure to mixtures of (anti-)androgenic chemicals during pregnancy and the risk of cryptorchidism and/or hypospadias in offspring, using the total effective xenobiotic burden of anti-androgens (TEXB-AA) as a biomarker. A subsample of 29 cases (16 of cryptorchidism, 12 of hypospadias, and one of both disorders) and 60 healthy controls was nested in a cohort of male newborns recruited between October 2000 and July 2002. The (anti-)androgenic activity of placenta samples collected at delivery was assessed using TEXB-AA biomarker, combined with a bioassay-directed fractionation protocol that separated endogenous hormones from most (anti-)androgenic chemicals by normal-phase HPLC. The bioassay measures the androgen-induced luciferase activity and the inhibition of this pathway by (anti-)androgens. First, we collected 27 HPLC fractions in each placenta extract, which were all tested in the bioassay. The multivariable statistical analyses indicated a statistically significant positive dose-response association between the potent anti-androgenic activity of the HPLC fraction collected during minutes 1-2 (F2) and the risk of malformations (odds ratio: 2.33, 95% CI: 1.04-5.23). This study represents a novel approach for the estimation of combined effects of the total anti-androgenic load and the associations suggest an effect of environmental pollutants on the development of fetal reproductive tract.Free Spanish abstract: A Spanish translation of this abstract is freely available at http://www.reproduction-online.org/content/149/6/605/suppl/DC1.
authors.affiliation: Instituto de Investigación Biosanitaria ibs.GRANADASan Cecilio University Hospital, University of Granada, 18071 Granada, SpainCIBER en Epidemiología y Salud Pública (CIBERESP)Madrid, SpainSchool of Life SciencesUniversity of Sussex, Falmer, Brighton BN1 9QG, UKInstitute of the EnvironmentHealth and Societies, Brunel University London, Kingston Lane, Uxbridge UB8 3PH, UKBiosciencesCollege of Life and Environmental Sciences, University of Exeter, Stocker Road, Exeter EX4 4QD, UK Instituto de Investigación Biosanitaria ibs.GRANADASan Cecilio University Hospital, University of Granada, 18071 Granada, SpainCIBER en Epidemiología y Salud Pública (CIBERESP)Madrid, SpainSchool of Life SciencesUniversity of Sussex, Falmer, Brighton BN1 9QG, UKInstitute of the EnvironmentHealth and Societies, Brunel University London, Kingston Lane, Uxbridge UB8 3PH, UKBiosciencesCollege of Life and Environmental Sciences, University of Exeter, Stocker Road, Exeter EX4 4QD, UK jparrebola@ugr.es.
authors.forename: Juan P
authors.initials: JP
authors.lastname: Arrebola
authors.affiliation: Instituto de Investigación Biosanitaria ibs.GRANADASan Cecilio University Hospital, University of Granada, 18071 Granada, SpainCIBER en Epidemiología y Salud Pública (CIBERESP)Madrid, SpainSchool of Life SciencesUniversity of Sussex, Falmer, Brighton BN1 9QG, UKInstitute of the EnvironmentHealth and Societies, Brunel University London, Kingston Lane, Uxbridge UB8 3PH, UKBiosciencesCollege of Life and Environmental Sciences, University of Exeter, Stocker Road, Exeter EX4 4QD, UK Instituto de Investigación Biosanitaria ibs.GRANADASan Cecilio University Hospital, University of Granada, 18071 Granada, SpainCIBER en Epidemiología y Salud Pública (CIBERESP)Madrid, SpainSchool of Life SciencesUniversity of Sussex, Falmer, Brighton BN1 9QG, UKInstitute of the EnvironmentHealth and Societies, Brunel University London, Kingston Lane, Uxbridge UB8 3PH, UKBiosciencesCollege of Life and Environmental Sciences, University of Exeter, Stocker Road, Exeter EX4 4QD, UK.
authors.forename: José M
authors.initials: JM
authors.lastname: Molina-Molina
authors.affiliation: Instituto de Investigación Biosanitaria ibs.GRANADASan Cecilio University Hospital, University of Granada, 18071 Granada, SpainCIBER en Epidemiología y Salud Pública (CIBERESP)Madrid, SpainSchool of Life SciencesUniversity of Sussex, Falmer, Brighton BN1 9QG, UKInstitute of the EnvironmentHealth and Societies, Brunel University London, Kingston Lane, Uxbridge UB8 3PH, UKBiosciencesCollege of Life and Environmental Sciences, University of Exeter, Stocker Road, Exeter EX4 4QD, UK Instituto de Investigación Biosanitaria ibs.GRANADASan Cecilio University Hospital, University of Granada, 18071 Granada, SpainCIBER en Epidemiología y Salud Pública (CIBERESP)Madrid, SpainSchool of Life SciencesUniversity of Sussex, Falmer, Brighton BN1 9QG, UKInstitute of the EnvironmentHealth and Societies, Brunel University London, Kingston Lane, Uxbridge UB8 3PH, UKBiosciencesCollege of Life and Environmental Sciences, University of Exeter, Stocker Road, Exeter EX4 4QD, UK.
authors.forename: Mariana F
authors.initials: MF
authors.lastname: Fernández
authors.affiliation: Instituto de Investigación Biosanitaria ibs.GRANADASan Cecilio University Hospital, University of Granada, 18071 Granada, SpainCIBER en Epidemiología y Salud Pública (CIBERESP)Madrid, SpainSchool of Life SciencesUniversity of Sussex, Falmer, Brighton BN1 9QG, UKInstitute of the EnvironmentHealth and Societies, Brunel University London, Kingston Lane, Uxbridge UB8 3PH, UKBiosciencesCollege of Life and Environmental Sciences, University of Exeter, Stocker Road, Exeter EX4 4QD, UK.
authors.forename: Jose M
authors.initials: JM
authors.lastname: Sáenz
authors.affiliation: Instituto de Investigación Biosanitaria ibs.GRANADASan Cecilio University Hospital, University of Granada, 18071 Granada, SpainCIBER en Epidemiología y Salud Pública (CIBERESP)Madrid, SpainSchool of Life SciencesUniversity of Sussex, Falmer, Brighton BN1 9QG, UKInstitute of the EnvironmentHealth and Societies, Brunel University London, Kingston Lane, Uxbridge UB8 3PH, UKBiosciencesCollege of Life and Environmental Sciences, University of Exeter, Stocker Road, Exeter EX4 4QD, UK Instituto de Investigación Biosanitaria ibs.GRANADASan Cecilio University Hospital, University of Granada, 18071 Granada, SpainCIBER en Epidemiología y Salud Pública (CIBERESP)Madrid, SpainSchool of Life SciencesUniversity of Sussex, Falmer, Brighton BN1 9QG, UKInstitute of the EnvironmentHealth and Societies, Brunel University London, Kingston Lane, Uxbridge UB8 3PH, UKBiosciencesCollege of Life and Environmental Sciences, University of Exeter, Stocker Road, Exeter EX4 4QD, UK.
authors.forename: Esperanza
authors.initials: E
authors.lastname: Amaya
authors.affiliation: Instituto de Investigación Biosanitaria ibs.GRANADASan Cecilio University Hospital, University of Granada, 18071 Granada, SpainCIBER en Epidemiología y Salud Pública (CIBERESP)Madrid, SpainSchool of Life SciencesUniversity of Sussex, Falmer, Brighton BN1 9QG, UKInstitute of the EnvironmentHealth and Societies, Brunel University London, Kingston Lane, Uxbridge UB8 3PH, UKBiosciencesCollege of Life and Environmental Sciences, University of Exeter, Stocker Road, Exeter EX4 4QD, UK.
authors.forename: Paolo
authors.initials: P
authors.lastname: Indiveri
authors.affiliation: Instituto de Investigación Biosanitaria ibs.GRANADASan Cecilio University Hospital, University of Granada, 18071 Granada, SpainCIBER en Epidemiología y Salud Pública (CIBERESP)Madrid, SpainSchool of Life SciencesUniversity of Sussex, Falmer, Brighton BN1 9QG, UKInstitute of the EnvironmentHealth and Societies, Brunel University London, Kingston Lane, Uxbridge UB8 3PH, UKBiosciencesCollege of Life and Environmental Sciences, University of Exeter, Stocker Road, Exeter EX4 4QD, UK.
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Hill
authors.affiliation: Instituto de Investigación Biosanitaria ibs.GRANADASan Cecilio University Hospital, University of Granada, 18071 Granada, SpainCIBER en Epidemiología y Salud Pública (CIBERESP)Madrid, SpainSchool of Life SciencesUniversity of Sussex, Falmer, Brighton BN1 9QG, UKInstitute of the EnvironmentHealth and Societies, Brunel University London, Kingston Lane, Uxbridge UB8 3PH, UKBiosciencesCollege of Life and Environmental Sciences, University of Exeter, Stocker Road, Exeter EX4 4QD, UK.
authors.forename: Martin
authors.initials: M
authors.lastname: Scholze
authors.affiliation: Instituto de Investigación Biosanitaria ibs.GRANADASan Cecilio University Hospital, University of Granada, 18071 Granada, SpainCIBER en Epidemiología y Salud Pública (CIBERESP)Madrid, SpainSchool of Life SciencesUniversity of Sussex, Falmer, Brighton BN1 9QG, UKInstitute of the EnvironmentHealth and Societies, Brunel University London, Kingston Lane, Uxbridge UB8 3PH, UKBiosciencesCollege of Life and Environmental Sciences, University of Exeter, Stocker Road, Exeter EX4 4QD, UK.
authors.forename: Frances
authors.initials: F
authors.lastname: Orton
authors.affiliation: Instituto de Investigación Biosanitaria ibs.GRANADASan Cecilio University Hospital, University of Granada, 18071 Granada, SpainCIBER en Epidemiología y Salud Pública (CIBERESP)Madrid, SpainSchool of Life SciencesUniversity of Sussex, Falmer, Brighton BN1 9QG, UKInstitute of the EnvironmentHealth and Societies, Brunel University London, Kingston Lane, Uxbridge UB8 3PH, UKBiosciencesCollege of Life and Environmental Sciences, University of Exeter, Stocker Road, Exeter EX4 4QD, UK.
authors.forename: Andreas
authors.initials: A
authors.lastname: Kortenkamp
authors.affiliation: Instituto de Investigación Biosanitaria ibs.GRANADASan Cecilio University Hospital, University of Granada, 18071 Granada, SpainCIBER en Epidemiología y Salud Pública (CIBERESP)Madrid, SpainSchool of Life SciencesUniversity of Sussex, Falmer, Brighton BN1 9QG, UKInstitute of the EnvironmentHealth and Societies, Brunel University London, Kingston Lane, Uxbridge UB8 3PH, UKBiosciencesCollege of Life and Environmental Sciences, University of Exeter, Stocker Road, Exeter EX4 4QD, UK Instituto de Investigación Biosanitaria ibs.GRANADASan Cecilio University Hospital, University of Granada, 18071 Granada, SpainCIBER en Epidemiología y Salud Pública (CIBERESP)Madrid, SpainSchool of Life SciencesUniversity of Sussex, Falmer, Brighton BN1 9QG, UKInstitute of the EnvironmentHealth and Societies, Brunel University London, Kingston Lane, Uxbridge UB8 3PH, UKBiosciencesCollege of Life and Environmental Sciences, University of Exeter, Stocker Road, Exeter EX4 4QD, UK.
authors.forename: Nicolás
authors.initials: N
authors.lastname: Olea
mesh_terms: D000328:Adult; D000726:Androgen Antagonists / Q000633:toxicity*; D015415:Biomarkers / Q000378:metabolism; D016022:Case-Control Studies; D003456:Cryptorchidism / Q000139:chemically induced*; D052244:Endocrine Disruptors / Q000633:toxicity*; D005260:Female; D006801:Humans; D007021:Hypospadias / Q000139:chemically induced*; D007231:Infant, Newborn; D008297:Male; D018811:Maternal Exposure; D010920:Placenta / Q000187:drug effects* / Q000378:metabolism; D011247:Pregnancy
chemical_list: D000726:Androgen Antagonists; D015415:Biomarkers; D052244:Endocrine Disruptors