title: A negative correlation between insulin-like peptide 3 and bisphenol A in human cord blood suggests an effect of endocrine disruptors on testicular descent during fetal development.
abstract: OBJECTIVE
  Does a relationship exist between insulin-like peptide 3 (INSL3) and selected environmental endocrine disruptors (EEDs) in human cord blood (cb)?
  
  
  CONCLUSIONS
  In the whole population (cryptorchid and control boys) cbINSL3 correlated negatively with cb free bisphenol A (BPA) providing indirect evidence for an impact of EEDs on fetal Leydig cell INSL3 production.
  
  
  BACKGROUND
  INSL3 is a major regulator of testicular descent. This hormone has been shown to be decreased in cord blood from boys with idiopathic cryptorchidism, the most frequent male malformation. Fetal exposure to several EEDs has been suspected to be involved in the occurrence of idiopathic cryptorchidism.
  
  
  METHODS
  Correlations between cb INSL3 or testosterone and cb free bioactive BPA and maternal milk polychlorinated biphenyls (PCB153), dichlorodiphenyldichloroethylene (DDE), and monobutyl phthalate (mBP) were assessed in newborn boys in a prospective case-control study. All boys (n = 6246) born after 34 weeks of gestation were systematically screened at birth for cryptorchidism over a 3-year period (2002-2005), and a diagnosis of cryptorchidism confirmed by a senior paediatrician.
  
  
  METHODS
  We studied 52 cryptorchid (26 transient, 26 persistent) and 128 control boys born at two hospitals in southern France. INSL3 was assayed in CB by a modified validated enzyme-linked immunosorbent assay. Testosterone was measured in CB after diethyl-ether extraction by means of ultra-pressure liquid chromatography-tandem mass spectrometry. Free cbBPA was measured after an extraction step with a radioimmunoassay validated after comparison of values obtained by high-pressure liquid chromatography-mass spectrometry. The xenobiotic analysis in mothers' milk was performed after fat extraction by gas chromatography-mass spectrometry.
  
  
  RESULTS
  EED concentrations were not increased in the cryptorchid versus control group although a trend for increased mBP (P = 0.09) was observed. In the whole study population, cb levels of BPA correlated negatively with INSL3 (P = 0.01; R² = 0.05) but not with testosterone. No other EED correlated with INSL3 or with testosterone.
  
  
  CONCLUSIONS
  The levels of BPA and INSL3 in cb may not reflect chronic fetal exposure to EEDs. The deleterious impact of EEDs on fetal testicular descent during specific windows of development has yet to be demonstrated.
  
  
  CONCLUSIONS
  The negative correlation between cb free BPA and INSL3 provides indirect evidence for an impact of EEDs on human fetal Leydig cell INSL3 production and points to cbINSL3 as a possible target of EED action during fetal testis development.
authors.affiliation: Department of Endocrinology, Diabetology and Reproductive Medicine, CHU Nice, Nice, France Institut National de la Recherche Médicale, UMR U1065, Université Nice-Sophia Antipolis, Nice, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Chevalier
authors.affiliation: Department of Endocrinology, Diabetology and Reproductive Medicine, CHU Nice, Nice, France Institut National de la Recherche Médicale, UMR U1065, Université Nice-Sophia Antipolis, Nice, France.
authors.forename: Françoise
authors.initials: F
authors.lastname: Brucker-Davis
authors.affiliation: Department of Hormonology and Metabolic Disorders, Hôpital Cochin, APHP, Paris-Descartes University, Paris, France.
authors.forename: Najiba
authors.initials: N
authors.lastname: Lahlou
authors.affiliation: Institut Sophia-Agrobiotech [INRA-CNRS, Nice University], 06903 Sophia-Antipolis, France.
authors.forename: Patrick
authors.initials: P
authors.lastname: Coquillard
authors.affiliation: Institut National de la Recherche Médicale U1060 CaRMen, Fédération d'Endocrinologie, Hospices civils de Lyon, Université Lyon-1, Bron, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Pugeat
authors.affiliation: Laboratoire de l'Environnement de la Ville de Nice, Nice, France.
authors.forename: Patricia
authors.initials: P
authors.lastname: Pacini
authors.affiliation: Department of Biochemistry, CHU Nice, France.
authors.forename: Patricia
authors.initials: P
authors.lastname: Panaïa-Ferrari
authors.affiliation: Department of Paediatrics, CHU Nice, Nice, France.
authors.forename: Kathy
authors.initials: K
authors.lastname: Wagner-Mahler
authors.affiliation: Department of Endocrinology, Diabetology and Reproductive Medicine, CHU Nice, Nice, France Institut National de la Recherche Médicale, UMR U1065, Université Nice-Sophia Antipolis, Nice, France fenichel.p@chu-nice.fr.
authors.forename: Patrick
authors.initials: P
authors.lastname: Fénichel
mesh_terms: D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D015331:Cohort Studies; D003456:Cryptorchidism / Q000097:blood / Q000139:chemically induced* / Q000175:diagnosis / Q000453:epidemiology; D052244:Endocrine Disruptors / Q000097:blood / Q000633:toxicity*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005312:Fetal Blood; D047109:Fetal Development / Q000187:drug effects*; D005602:France / Q000453:epidemiology; D006801:Humans; D007231:Infant, Newborn; D007328:Insulin / Q000097:blood / Q000378:metabolism; D000078790:Insulin Secretion; D007985:Leydig Cells / Q000187:drug effects / Q000378:metabolism; D008297:Male; D018811:Maternal Exposure / Q000009:adverse effects*; D015997:Neonatal Screening; D011247:Pregnancy; D011446:Prospective Studies; D011506:Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011863:Radioimmunoassay; D012306:Risk; D013737:Testis / Q000187:drug effects* / Q000196:embryology / Q000378:metabolism
chemical_list: D015415:Biomarkers; D052244:Endocrine Disruptors; D007328:Insulin; C084797:Leydig insulin-like protein; D011506:Proteins
keywords: bisphenol A; cryptorchidism; fetal exposure to endocrine disruptors; human testicular descent; insulin-like peptide 3