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Institut Sophia Agrobiotech

UMR INRA - Univ. Nice Sophia Antipolis - Cnrs

Human reproduction

22 December 2014

Human reproduction
© The European Society of Human Reproduction and Embryology
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.


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; R2 = 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.

STUDY FUNDING/COMPETING INTEREST(S) This project was sponsored by the Clinical Research Board of Nice University Hospital and supported by a grant from the French Research Ministry and from the Department of Hormonology and Metabolic Disorders, Hôpital Cochin, APHP, Paris-Descartes University, France. There are no conflicts of interest to declare.                      

Key words : insulin-like peptide 3, human testicular descent, cryptorchidism, bisphenol A, fetal exposure to endocrine disruptors

Chevalier, N., Brucker-Davis, F., Lahlou, N., Coquillard, P., Pugeat, M., Pacini, P., Panaïa-Ferrari, P., Wagner-Mahler, K., and Fénichel, P. (2014). 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. Hum. Reprod. deu340.
 DOI: 10.1093/humrep/deu340.

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