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Sertraline Alters Multidrug Resistance Phosphoglycoprotein Activity in the Mouse Placenta and Fetal Blood–Brain Barrier

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Abstract

Phosphoglycoprotein (P-gp) is highly expressed in the placental syncytiotrophoblast and prevents xenobiotics from entering the fetus. In tumor cells, P-gp-mediated substrate efflux is inhibited by selective serotonin reuptake inhibitors (SSRIs). However, nothing is known regarding the effects of SSRIs on P-gp function in the placenta or fetal tissues. We hypothesized that the SSRI sertraline would decrease P-gp-mediated drug efflux at the placenta and fetal blood–brain barrier (BBB)—increasing P-gp substrate transfer from the mother to the fetus and fetal brain. In contrast to our hypothesis, this study presents the novel findings that sertraline (4 hours exposure) increases placental P-gp-mediated efflux (P < .001), resulting in decreased drug transfer to the fetus. Meanwhile, sertraline decreases fetal (P < .001) and maternal (P < .05) BBB P-gp-mediated efflux, resulting in increased drug transfer into the fetal and maternal brain from the circulation. This suggests that P-gp regulation by sertraline is tissue specific. These findings have important clinical implications with respect to fetal protection during maternal drug therapy in pregnancy.

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Authors and Affiliations

  1. Department of Physiology, University of Toronto, 1 King’s College Circle, Toronto , Ontario, M5S1A8, Canada

    Manzerul Bhuiyan MSc, Sophie Petropoulos PhD & Stephen G. Matthews PhD

  2. Department of Obstetrics and Gynecology, University of Ottawa, Ottawa, Canada

    William Gibb PhD

  3. Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Canada

    William Gibb PhD

  4. Department of Obstetrics and Gynecology, Faculty of Medicine, University of Toronto, Toronto, Canada

    Stephen G. Matthews PhD

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  1. Manzerul Bhuiyan MSc
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  2. Sophie Petropoulos PhD
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  4. Stephen G. Matthews PhD
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Correspondence to Stephen G. Matthews PhD.

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Bhuiyan, M., Petropoulos, S., Gibb, W. et al. Sertraline Alters Multidrug Resistance Phosphoglycoprotein Activity in the Mouse Placenta and Fetal Blood–Brain Barrier. Reprod. Sci. 19, 407–415 (2012). https://doi.org/10.1177/1933719111424438

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