Accéder directement au contenu Accéder directement à la navigation
Article dans une revue

Ibuprofen results in alterations of human fetal testis development

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.
Type de document :
Article dans une revue
Liste complète des métadonnées

Littérature citée [75 références]  Voir  Masquer  Télécharger

https://hal-univ-rennes1.archives-ouvertes.fr/hal-01517095
Déposant : Xavier Chard-Hutchinson <>
Soumis le : jeudi 28 juin 2018 - 09:14:15
Dernière modification le : mercredi 14 octobre 2020 - 04:22:48

Fichier

Maamar_Ibuprofen results in al...
Fichiers éditeurs autorisés sur une archive ouverte

Licence


Distributed under a Creative Commons Paternité 4.0 International License

Identifiants

Citation

M. Ben Maamar, Lauriane Lesné, K. Hennig, C. Desdoits-Lethimonier, K.R. Kilcoyne, et al.. Ibuprofen results in alterations of human fetal testis development. Scientific Reports, Nature Publishing Group, 2017, 7 (1), pp.44184. ⟨10.1038/srep44184⟩. ⟨hal-01517095⟩

Partager

Métriques

Consultations de la notice

529

Téléchargements de fichiers

331