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

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.
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https://hal-pasteur.archives-ouvertes.fr/pasteur-01421114
Contributor : Michel Courcelles <>
Submitted on : Wednesday, December 21, 2016 - 3:57:49 PM
Last modification on : Friday, March 27, 2020 - 3:18:04 PM

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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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