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

Autor: Kathy Wagner-Mahler, Michel Pugeat, Najiba Lahlou, Françoise Brucker-Davis, Patricia Pacini, Patricia Panaïa-Ferrari, Patrick Coquillard, N. Chevalier, Patrick Fénichel
Přispěvatelé: Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National de la Recherche Agronomique (INRA), Clinical Research Board of Nice University Hospital, French Research Ministry, Department of Hormonology and Metabolic Disorders, Hopital Cochin, APHP, Paris-Descartes University, France, Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL)
Jazyk: angličtina
Rok vydání: 2015
Předmět:
Male
Testis/*drug effects/embryology/secretion
[SDV]Life Sciences [q-bio]
Endocrine Disruptors
France/epidemiology
Fetal Development
Cohort Studies
Pregnancy
Cryptorchidism
Insulin Secretion
Testis
Insulin
Prospective Studies
Testosterone
education.field_of_study
Endocrine Disruptors/blood/*toxicity
Leydig cell
Rehabilitation
Obstetrics and Gynecology
Leydig Cells
Fetal Blood
3. Good health
medicine.anatomical_structure
Maternal Exposure
Cord blood
Gestation
Female
France
Cryptorchidism/blood/*chemically induced/diagnosis/epidemiology
Risk
medicine.medical_specialty
endocrine system
Population
Radioimmunoassay
Enzyme-Linked Immunosorbent Assay
Neonatal Screening
Internal medicine
medicine
Endocrine system
Proteins/*antagonists & inhibitors/secretion
Humans
Insulin/blood/secretion
education
Fetus
business.industry
Fetal Development/*drug effects
Infant
Newborn
Proteins
Infant
Newborn
Endocrinology
Reproductive Medicine
Case-Control Studies
Maternal Exposure/*adverse effects
business
Biomarkers
Biomarkers/blood
Hormone
Leydig Cells/drug effects/secretion
Zdroj: Human Reproduction
Human Reproduction, Oxford University Press (OUP), 2015, 30 (2), pp.447-53. ⟨10.1093/humrep/deu340⟩
ISSN: 0268-1161
1460-2350
Popis: International audience; STUDY QUESTION: Does a relationship exist between insulin-like peptide 3 (INSL3) and selected environmental endocrine disruptors (EEDs) in human cord blood (cb)? SUMMARY ANSWER: 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. WHAT IS KNOWN ALREADY: 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. STUDY DESIGN, SIZE, DURATION: 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. PARTICIPANTS/MATERIALS, SETTING, 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. MAIN RESULTS AND THE ROLE OF CHANCE: 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; R(2) = 0.05) but not with testosterone. No other EED correlated with INSL3 or with testosterone. LIMITATIONS, REASONS FOR CAUTION: 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. WIDER IMPLICATIONS OF THE FINDINGS: 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.
Databáze: OpenAIRE
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