Abstract

Amino acid transporters expressed in the placenta help to regulate the transfer of amino acids from maternal to fetal circulation. Nutritional or hormonal factors are known to potentially impact the expression of amino acid transporters in the placenta. A relatively new field of inquiry has also demonstrated that inflammation, whether associated with infection or not, also alters the expression of amino acid transporters in the placenta. Indeed, studies over the past 15 years have demonstrated that malaria, viral and bacterial models of infection, preeclampsia, and direct administration of proinflammatory cytokines can alter placental amino acid transporter expression. While such studies have largely focused on System A and System L transporters, other transporters are also affected. p38 MAPK, STAT3, mTORC1, and AMPK signaling have all been implicated in these changes, but the underlying mechanism(s) remain to be fully elucidated. Furthermore, the implications of such changes warrant further investigation. This review will summarize studies that have investigated the impact of inflammation on placental amino acid transporter expression, identify questions that remain unanswered, and propose future areas of research to advance the field. As amino acid transporters are now being considered for drug targeting and drug delivery, furthering our understanding of the regulation of these transporters during disease states will be of increasing clinical value.

Significance Statement While this is a relatively new field of research, multiple studies have demonstrated that inflammation alters placental amino acid transporter expression. This review will serve to summarize, for the first time, studies in this field and identify gaps in current knowledge as research in this area moves beyond identifying changes in transporter expression to investigating the implications of such changes and the mechanisms underlying them.