Gestational Age Variation in Human Placental Drug Transporters

Authors

Laura Goetzl
Nune Darbinian
Nana Merabova
Lindsay C Devane
Sammanda Ramamoorthy

Publication Date

4-6-2022

Journal

Frontiers in Pharmacology

Abstract

Patient and providers' fear of fetal exposure to medications may lead to discontinuation of treatment, disease relapse, and maternal morbidity. Placental drug transporters play a critical role in fetal exposure through active transport but the majority of data are limited to the 3rd trimester, when the majority of organogenesis has already occurred. Our objective was to define gestational age (GA) dependent changes in protein activity, expression and modifications of five major placental drug transporters: SERT, P-gp, NET, BCRP and MRP3. Apical brush border membrane fractions were prepared from fresh 1st, 2nd and 3rd trimester human placentas collected following elective pregnancy termination or planned cesarean delivery. A structured maternal questionnaire was used to identify maternal drug use and exclude exposed subjects. Changes in placental transporter activity and expression relative to housekeeping proteins were quantified. There was evidence for strong developmental regulation of SERT, NET, P-gp, BCRP and MRP3. P-gp and BCRP decreased with gestation (r = -0.72,

Keywords

placental transporters, serotonin transporter (5HTT), P-glycoprotein (ABCB1 protein), multidrug resistance protein 3 (MDR3), breast cancer resistance protein (BCRP or ABCG2), norepinephrine transporter, placental drug transport