Fluoxetine and its active metabolite norfluoxetine disrupt estrogen synthesis in a co-culture model of the feto-placental unit.

Andrée-Anne Hudon Thibeault 1, 2, 3 Laetitia Laurent 2, 3, 1 Sung Vo Duy 4 Sébastien Sauvé 5 Patrick Caron 5 Chantal Guillemette 5 J Thomas Sanderson 2 Cathy Vaillancourt 2, 3, 1
1 CINBIOSE - UQUAM
2 INRS-IAF - Institut Armand Frappier
3 BioMed Research Center
4 University of Montréal
5 Centre de Recherche du Centre Hospitalier Universitaire de Québec
Abstract : 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.
Keywords : 5-HT(2A) receptor Aromatase (CYP19) Feto-placental steroidogenesis Human Selective serotonin-reuptake inhibitors (SSRI) Serotonin transporter (SERT)
Type de document :
Article dans une revue
Molecular and Cellular Endocrinology, Elsevier, 2016, 442, pp.32-39. 〈10.1016/j.mce.2016.11.021〉
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https://hal-pasteur.archives-ouvertes.fr/pasteur-01421114
Contributeur : Michel Courcelles <>
Soumis le : mercredi 21 décembre 2016 - 15:57:49
Dernière modification le : jeudi 20 septembre 2018 - 13:16:05

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Andrée-Anne Hudon Thibeault, Laetitia Laurent, Sung Vo Duy, Sébastien Sauvé, Patrick Caron, et al.. Fluoxetine and its active metabolite norfluoxetine disrupt estrogen synthesis in a co-culture model of the feto-placental unit.. Molecular and Cellular Endocrinology, Elsevier, 2016, 442, pp.32-39. 〈10.1016/j.mce.2016.11.021〉. 〈pasteur-01421114〉

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