Ibuprofen is deleterious for the development of first trimester human fetal ovary ex vivo

Autor: Leverrier-Penna, S., Mitchell, R. T., Becker, E., Lecante, L., Ben Maamar, M., Homer, N., Lavoue, V., Kristensen, D. M., Dejucq-Rainsford, N., Jegou, B., Mazaud-Guittot, S.
Přispěvatelé: Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), École des Hautes Études en Santé Publique [EHESP] (EHESP), Queen's Medical Researche Institute, University of Edinburgh, CHU Pontchaillou [Rennes], Novo Nordisk Foundation Center for Protein Research (CPR), Faculty of Health and Medical Sciences, University of Copenhagen = Københavns Universitet (KU)-University of Copenhagen = Københavns Universitet (KU), HAP-2014-073, Agence Nationale de Sécurité du Médicament et des Produits de Santé, ANR-15-CE34-0001-01, Agence Nationale de la Recherche, 098522, Wellcome Trust, Danish Council for independent Research (Medical Sciences), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), University of Copenhagen = Københavns Universitet (UCPH)-University of Copenhagen = Københavns Universitet (UCPH), ANR-15-CE34-0001,ACETAMINOV,Antalgiques et différenciation ovarienne fœtale chez l'Homme(2015)
Jazyk: angličtina
Rok vydání: 2018
Předmět:
Zdroj: Human Reproduction
Human Reproduction, Oxford University Press (OUP), 2018, 33 (3), pp.482-493. ⟨10.1093/humrep/dex383⟩
Human Reproduction, 2018, 33 (3), pp.482-493. ⟨10.1093/humrep/dex383⟩
Leverrier-Penna, S, Mitchell, R, Becker, E B E, Lecante, L, Ben Maamar, M, Homer, N, Lavoué, V, Kristensen, D M, Dejucq-Rainsford, N, Jégou, B & Mazaud-guittot, S 2018, ' Ibuprofen is deleterious for the development of first trimester human fetal ovary ex vivo ', Human Reproduction . https://doi.org/10.1093/humrep/dex383
Leverrier-Penna, S, Mitchell, R T, Becker, E, Lecante, L, Ben Maamar, M, Homer, N, Lavoue, V, Kristensen, D M, Dejucq-Rainsford, N, Jegou, B & Mazaud-Guittot, S 2018, ' Ibuprofen is deleterious for the development of first trimester human fetal ovary ex vivo ', Human Reproduction, vol. 33, no. 3, pp. 482-493 . https://doi.org/10.1093/humrep/dex383
ISSN: 0268-1161
1460-2350
Popis: International audience; STUDY QUESTION Does ibuprofen use during the first trimester of pregnancy interfere with the development of the human fetal ovary? SUMMARY ANSWER In human fetuses, ibuprofen exposure is deleterious for ovarian germ cells. WHAT IS KNOWN ALREADY In utero stages of ovarian development define the future reproductive capacity of a woman. In rodents, analgesics can impair the development of the fetal ovary leading to early onset of fertility failure. Ibuprofen, which is available over-the-counter, has been reported as a frequently consumed medication during pregnancy, especially during the first trimester when the ovarian germ cells undergo crucial steps of proliferation and differentiation. STUDY DESIGN, SIZE, DURATION Organotypic cultures of human ovaries obtained from 7 to 12 developmental week (DW) fetuses were exposed to ibuprofen at 1-100 μM for 2, 4 or 7 days. For each individual, a control culture (vehicle) was included and compared to its treated counterpart. A total of 185 individual samples were included. PARTICIPANTS/MATERIALS, SETTING, METHODS Ovarian explants were analyzed by flow cytometry, immunohistochemistry and quantitative PCR. Endpoints focused on ovarian cell number, cell death, proliferation and germ cell complement. To analyze the possible range of exposure, ibuprofen was measured in the umbilical cord blood from the women exposed or not to ibuprofen prior to termination of pregnancy. MAIN RESULTS AND THE ROLE OF CHANCE Human ovarian explants exposed to 10 and 100 μM ibuprofen showed reduced cell number, less proliferating cells, increased apoptosis and a dramatic loss of germ cell number, regardless of the gestational age of the fetus. Significant effects were observed after 7 days of exposure to 10 μM ibuprofen. At this concentration, apoptosis was observed as early as 2 days of treatment, along with a decrease in M2A-positive germ cell number. These deleterious effects of ibuprofen were not fully rescued after 5 days of drug withdrawal. LARGE SCALE DATA N/A. LIMITATIONS, REASONS FOR CAUTION This study was performed in an experimental setting of human ovaries explants exposed to the drug in culture, which may not fully recapitulate the complexity of in vivo exposure and organ development. Inter-individual variability is also to be taken into account. WIDER IMPLICATIONS OF THE FINDINGS Whereas ibuprofen is currently only contra-indicated after 24 weeks of pregnancy, our results points to a deleterious effect of this drug on first trimester fetal ovaries ex vivo. These findings deserve to be considered in light of the present recommendations about ibuprofen consumption pregnancy, and reveal the urgent need for further investigations on the cellular and molecular mechanisms that underlie the effect of ibuprofen on fetal ovary development. © The Author(s) 2018. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology.
Databáze: OpenAIRE
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