Advancing Pregnancy and Pediatric Science through the NIH Transporter Elucidation Network

Human gestation is characterized by dynamic changes in maternal physiology and maturation of tissue functions before and after birth. The fetus and neonate are highly dependent upon transfer of maternal nutrients via the placenta and lactating mammary gland, which frequently involve selective membrane transporter proteins. At the same time, developmental changes in fetal and infant transport mechanisms critical for regulating absorption at the intestinal and blood-brain barriers are occurring. Coordinate regulation of cellular entry and efflux of nutrients, supplements, and xenobiotics, including drugs and environmental chemicals, must occur during this critical developmental period. In 2023, the National Institutes of Health launched the Transporter Elucidation Network (TEN) across four centers. This initiative applies experimental, computational, and translational approaches to (1) identify SoLute Carrier (SLC) superfamily and ATP-binding cassette (ABC) transporters in the human placenta, mammary gland, as well as the pediatric brain and intestinal barriers and, (2) characterize their localization, expression, function, and regulation. The Network seeks to identify functional determinants of transporters as gatekeepers of entry to placenta, mammary gland and brain, and applies structural biology, proteomics, metabolomics, organoids, liquid biopsies, and microphysiological systems to this end. Computational strategies, such as machine learning, virtual screening, physiologically based pharmacokinetics, and perinatal epidemiology complement our experimental approaches. This paper highlights the TEN's multidisciplinary strategies to address current challenges in perinatal and pediatric transporter research and its commitment to advancing state-of-the-art tools and new approach methodologies to fill critical gaps in our understanding of nutrient and xenobiotic exposure during early human development.