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Effects of Neonicotinoids on Aromatase(CYP19) Activity and Hormone Production in a Fetoplacental Co-Culture Model

Sanderson, J. Thomas; Caron-Beaudoin, Elyse; Viau, Mélanie; Hudon-Thibeault, Andrée-Anne; Vaillancourt, Cathy . Effects of Neonicotinoids on Aromatase(CYP19) Activity and Hormone Production in a Fetoplacental Co-Culture Model In: Society of Toxicology (SOT), 56th annual meeting, 12-16 mars 2017, Baltimore.

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Résumé

Aromatase (CYP19) is a key enzyme in the biosynthesis of estrogens and it is expressed in a promoter- and tissue-specific manner. Estrogens are critical for healthy pregnancy and in the placenta, CYP19 is highly expressed via its unique placental I.1 promoter. Little is known about the endocrine disrupting potential of neonicotinoid insecticides on CYP19 expression, but impaired estrogen production during pregnancy can lead to adverse pregnancy outcomes. We determined the effects of imidacloprid, thiacloprid and thiamethoxam (0.1-10 μM) on aromatase activity and hormone production in a co-culture model representing the feto-placental steroidogenic unit. H295R cells with fetal adrenocortical characteristics and BeWo trophoblast-like cells were co-cultured and exposed to each of the three neonicotinoids for 24h. Aromatase activity in fetal (H295R) and placental (BeWo) compartments were measured by tritiated water-release assay. Estradiol, estrone, estriol, dehydroepiandrosterone (DHEA), androstenedione and β-human chorionic gonadotropin (β-hCG) production was determined by ELISA. In the co-culture, all three neonicotinoids increased aromatase activity in H295R and BeWo cells. Thiacloprid and thiamethoxam induced estradiol, estrone, DHEA and β-hCG production, but inhibited estriol synthesis. Imidacloprid induced estradiol, DHEA and β-hCG production, and also inhibited estriol production, but had no effect on estrone production. Inhibition of pregnancy-specific estriol may be related to the metabolism of neonicotinoids by fetal CYP3A7, which is also the key enzyme producing the 16α-hydroxylated metabolite of DHEA that is eventually converted to estriol by placental aromatase. This is the first report of the successful use of this unique feto-placental co-culture model as a screening tool for the potential endocrine disrupting effects of neonicotinoids on hormone production and aromatase activity during pregnancy.

Type de document: Document issu d'une conférence ou d'un atelier
Informations complémentaires: The Toxicologist 156:149. Abstract #1507
Mots-clés libres: -
Centre: Centre INRS-Institut Armand Frappier
Date de dépôt: 10 sept. 2018 20:49
Dernière modification: 10 sept. 2018 20:49
URI: http://espace.inrs.ca/id/eprint/7519

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