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

Thibeault, Andrée-Anne; Laurent, Laetitia; Duy, Sung Vo; Sauvé, Sébastien; Caron, Patrick; Guillemette, Chantale; Sanderson, J. Thomas; Vaillancourt, Cathy (2017). Fluoxetine and its active metabolite norfluoxetine disrupt estrogen synthesis in a co-culture model of the feto-placental unit Molecular and Cellular Endocrinology , vol. 15 , nº 442. p. 32-39. DOI: 10.1016/j.mce.2016.11.021.

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Résumé

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.

Type de document:
Mots-clés libres: 5-HT(2A) receptor; Aromatase (CYP19); Feto-placental steroidogenesis; Human; Selective serotonin-reuptake inhibitors (SSRI); Serotonin transporter (SERT)
Centre: Centre INRS-Institut Armand Frappier
Date de dépôt: 29 juin 2017 05:37
Dernière modification: 29 juin 2017 05:37
URI: http://espace.inrs.ca/id/eprint/5303

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