Thibeault, Andrée-Anne; Laurent, Laetitia; Duy, Sung Vo; Sauvé, Sébastien; Caron, Patrick; Guillemette, Chantale; Sanderson, J. Thomas et 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. pp. 32-39. DOI: 10.1016/j.mce.2016.11.021.
Ce document n'est pas hébergé sur EspaceINRS.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: | Article |
|---|---|
| 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: | https://espace.inrs.ca/id/eprint/5303 |
Gestion Actions (Identification requise)
 |
Modifier la notice |