Ibuprofen results in alterations of human fetal testis development View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2017-12

AUTHORS

Millissia Ben Maamar, Laurianne Lesné, Kristin Hennig, Christèle Desdoits-Lethimonier, Karen R Kilcoyne, Isabelle Coiffec, Antoine D Rolland, Cécile Chevrier, David M Kristensen, Vincent Lavoué, Jean-Philippe Antignac, Bruno Le Bizec, Nathalie Dejucq-Rainsford, Rod T Mitchell, Séverine Mazaud-Guittot, Bernard Jégou

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. More... »

PAGES

44184

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/srep44184

DOI

http://dx.doi.org/10.1038/srep44184

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1084132082

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/28281692


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