%0 Journal Article %T Fluoxetine and its active metabolite norfluoxetine disrupt estrogen synthesis in a co-culture model of the feto-placental unit. %+ UQUAM (CINBIOSE) %+ Institut Armand Frappier (INRS-IAF) %+ Université du Québec à Montréal = University of Québec in Montréal (UQAM) %+ University of Montréal %+ Centre de Recherche du Centre Hospitalier Universitaire de Québec %A Hudon Thibeault, Andrée-Anne %A Laurent, Laetitia %A Vo Duy, Sung %A Sauvé, Sébastien %A Caron, Patrick %A Guillemette, Chantal %A Sanderson, J Thomas %A Vaillancourt, Cathy %< avec comité de lecture %@ 0303-7207 %J Molecular and Cellular Endocrinology %I Elsevier %V 442 %P 32-39 %8 2016-11-24 %D 2016 %R 10.1016/j.mce.2016.11.021 %M 27890559 %K 5-HT(2A) receptor %K Aromatase (CYP19) %K Feto-placental steroidogenesis %K Human %K Selective serotonin-reuptake inhibitors (SSRI) %K Serotonin transporter (SERT) %Z Life Sciences [q-bio]Journal articles %X The effects of fluoxetine, one of the most prescribed selective serotonin-reuptake inhibitors (SSRIs) during pregnancy, and its active metabolite norfluoxetine were studied on placental aromatase (CYP19) and feto-placental steroidogenesis. Fluoxetine did not alter estrogen secretion in co-culture of fetal-like adrenocortical (H295R) and trophoblast-like (BeWo) cells used as a model of the feto-placental unit, although it induced CYP19 activity, apparently mediated by the serotonin (5-HT)2A receptor/PKC signaling pathway. Norfluoxetine decreased estrogen secretion in the feto-placental co-culture and competitively inhibited catalytic CYP19 activity in BeWo cells. Decreased serotonin transporter (SERT) activity in the co-culture was comparable to 17β-estradiol treatment of BeWo cells. This work shows that the complex interaction of fluoxetine and norfluoxetine with placental estrogen production, involves 5-HT-dependent and -independent mechanisms. Considering the crucial role of estrogens during pregnancy, our results raise concern about the impact of SSRI treatment on placental function and fetal health. %G English %L pasteur-01421114 %U https://pasteur.hal.science/pasteur-01421114 %~ PASTEUR %~ RIIP %~ INRS-IAF