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Sci Rep. 2017 Mar 10;7:44184. doi: 10.1038/srep44184.

Ibuprofen results in alterations of human fetal testis development.

Author information

1
Institut national de la santé et de la recherche médicale (Inserm), Institut de recherche en santé, environnement et travail (Irset - Inserm UMR 1085), Université de Rennes 1, 9 Avenue Léon Bernard, F-35000 RENNES, France.
2
LUNAM Université, Oniris, USC INRA 1329, Laboratoire d'Etude des Résidus et Contaminants dans les Aliments (LABERCA), Nantes, F-44307, France.
3
MRC Centre for Reproductive Health, University of Edinburgh, Queens Medical Research Institute, 47 Little France Crescent, Edinburgh, EH16 4TJ, UK.
4
Laboratorium of Genomic and Molecular Biomedicine, Department of Biology, University of Copenhagen, Ole Maaløes Vej 5, DK-2200 Copenhagen N, Denmark.
5
CHU de Rennes, Service de Gynécologie, Hôpital Sud, 16, boulevard de Bulgarie, F-35700 Rennes, France.
6
Ecole des hautes études en santé publique (EHESP), Avenue Léon Bernard, F-35043 RENNES, France.

Abstract

Among pregnant women ibuprofen is one of the most frequently used pharmaceutical compounds with up to 28% reporting use. Regardless of this, it remains unknown whether ibuprofen could act as an endocrine disruptor as reported for fellow analgesics paracetamol and aspirin. To investigate this, we exposed human fetal testes (7-17 gestational weeks (GW)) to ibuprofen using ex vivo culture and xenograft systems. Ibuprofen suppressed testosterone and Leydig cell hormone INSL3 during culture of 8-9 GW fetal testes with concomitant reduction in expression of the steroidogenic enzymes CYP11A1, CYP17A1 and HSD17B3, and of INSL3. Testosterone was not suppressed in testes from fetuses younger than 8 GW, older than 10-12 GW, or in second trimester xenografted testes (14-17 GW). Ex vivo, ibuprofen also affected Sertoli cell by suppressing AMH production and mRNA expression of AMH, SOX9, DHH, and COL2A1. While PGE2 production was suppressed by ibuprofen, PGD2 production was not. Germ cell transcripts POU5F1, TFAP2C, LIN28A, ALPP and KIT were also reduced by ibuprofen. We conclude that, at concentrations relevant to human exposure and within a particular narrow 'early window' of sensitivity within first trimester, ibuprofen causes direct endocrine disturbances in the human fetal testis and alteration of the germ cell biology.

PMID:
28281692
PMCID:
PMC5345102
DOI:
10.1038/srep44184
[Indexed for MEDLINE]
Free PMC Article

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