Ibuprofen results in alterations of human fetal testis development

• DOI: 10.1038/srep44184
• Publication Date: 2017-03-10T10:24:05Z
• Authors: Millissia Ben Maamar; Laurianne Lesné; Kristin Hennig; Christèle Desdoit...; Karen R. Kilcoyne; Isabelle Coiffec; Antoine D. Rolland; Cécile Chevrier; David M. Kristensen; Vincent Lavoué; Jean-Philippe Ant...; Bruno Le Bizec; Nathalie Dejucq-R...; Rod T. Mitchell; Séverine Mazaud-G...; Bernard Jégou
• Keywords: Ibuprofen; Ex vivo; CYP17A1

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