Fluoxetine and its active metabolite norfluoxetine disrupt estrogen synthesis in a co-culture model of the feto-placental unit.
Mol Cell Endocrinol
; 442: 32-39, 2017 02 15.
Article
em En
| MEDLINE
| ID: mdl-27890559
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 17ß-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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Placenta
/
Fluoxetina
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Estrogênios
Limite:
Female
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Humans
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Pregnancy
Idioma:
En
Revista:
Mol Cell Endocrinol
Ano de publicação:
2017
Tipo de documento:
Article