{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T21:54:53Z","timestamp":1792101293939,"version":"4.4.0"},"posted":{"date-parts":[[2026,6,30]]},"group-title":"Pharmacology and Toxicology","reference-count":51,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T00:00:00Z","timestamp":1782777600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"award":["1UC2 HD113041"],"award-info":[{"award-number":["1UC2 HD113041"]}],"id":[{"id":"https:\/\/ror.org\/04byxyr05","id-type":"ROR","asserted-by":"publisher"}]},{"award":["5R24 HD000836"],"award-info":[{"award-number":["5R24 HD000836"]}],"id":[{"id":"https:\/\/ror.org\/04byxyr05","id-type":"ROR","asserted-by":"publisher"}]},{"award":["T32 GM007750"],"award-info":[{"award-number":["T32 GM007750"]}],"id":[{"id":"https:\/\/ror.org\/04q48ey07","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,6,30]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>The placenta serves a critical role in nutrient uptake and waste elimination for the developing fetus. The placenta is also responsible for the uptake and\/or exchange of xenobiotics, including medications, between the maternal and fetal bloodstreams. An estimated 40-80% of women take medications or drugs during pregnancy for a variety of conditions. Very little is understood about fetal drug and nutrient exposure during pregnancy and how it may change over the course of fetal development.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>This study aimed to characterize the abundance of transport proteins in placental tissue, which are important in modulating fetal nutrient and drug exposure, over the duration of pregnancy. Mass spectrometry-based global proteomic analysis revealed trends in the expression of thousands of proteins throughout gestation. Focusing on the membrane-associated proteome enabled an increased emphasis on the solute carrier and ATP-binding cassette families of transporter proteins that are critical for nutrient and xenobiotic transport across the maternal-fetal barrier.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Study Design<\/jats:title>\n                  <jats:p>Using data-independent acquisition proteomics, relative abundance of proteins in placental tissue samples was profiled across all three trimesters of pregnancy (Trimester 1 = 16, Trimester 2 = 9, and Term = 9). Membrane fractions were generated to enrich membrane-associated proteins for proteomic analysis. Placental samples were grouped into randomized batches for membrane fraction generation and mass spectrometry analysis. Proteomic search results from each batch were imported into the R programming environment from Skyline, concatenated, and normalized as one data set for downstream analysis.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>A total of 6,331 proteins were detected across all samples with 4,210 proteins identified in every sample. Pathway analysis revealed that as gestational age increases, membrane-associated proteins involved in more complex metabolic pathways increase in relative abundance while those involved in extracellular remodeling events and simple organic ion transport tended to decrease. A total of 139 solute carrier and ATP-binding cassette transport proteins were identified in all samples, and 80 were identified in every sample. In general, membrane-associated proteins, including solute carrier and ATP-binding cassette transport proteins, were significantly enriched in placental tissue collected during early gestation compared to term placental tissue.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>This study presents a comprehensive profiling of membrane-associated proteomic changes during gestation and identifies significant gestational age associated abundance changes at the protein level in several transport protein families. The application of data-independent acquisition global proteomic techniques enabled in-depth analysis of thousands of proteomic changes across pregnancy in a single experiment. These data provide critical information to support future studies into the understanding of fetal exposure to xenobiotics and nutrients circulating in the maternal bloodstream.<\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2026.06.25.730994","type":"posted-content","created":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T20:20:14Z","timestamp":1782850814000},"source":"Crossref","is-referenced-by-count":1,"title":["Proteomic profiling of xenobiotic and nutrient transporters in human placenta of different gestational ages"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-8873-1327","authenticated-orcid":false,"given":"Eric M.","family":"Weaver","sequence":"first","affiliation":[{"name":"Department of Pharmaceutics, School of Pharmacy, University of Washington, Seattle, Washington, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8909-4685","authenticated-orcid":false,"given":"Ariel","family":"Topletz-Erickson","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, School of Pharmacy, University of Washington, Seattle, Washington, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9548-3126","authenticated-orcid":false,"given":"Nina","family":"Isoherranen","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, School of Pharmacy, University of Washington, Seattle, Washington, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4820-8455","authenticated-orcid":false,"given":"Jashvant D.","family":"Unadkat","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, School of Pharmacy, University of Washington, Seattle, Washington, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8290-2347","authenticated-orcid":false,"given":"Samuel L.M.","family":"Arnold","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, School of Pharmacy, University of Washington, Seattle, Washington, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026070301250527000_2026.06.25.730994v1.1","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1097\/AOG.0000000000002579","article-title":"Prescription and Other Medication Use in Pregnancy","volume":"131","year":"2018","journal-title":"Obstet Gynecol"},{"key":"2026070301250527000_2026.06.25.730994v1.2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2023.12.020"},{"key":"2026070301250527000_2026.06.25.730994v1.3","doi-asserted-by":"crossref","first-page":"1758","DOI":"10.1007\/s43032-020-00173-y","article-title":"Changes in Placental Nutrient Transporter Protein Expression and Activity Across Gestation in Normal and Obese Women","volume":"27","year":"2020","journal-title":"Reprod Sci"},{"key":"2026070301250527000_2026.06.25.730994v1.4","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2018.12.024"},{"key":"2026070301250527000_2026.06.25.730994v1.5","doi-asserted-by":"crossref","first-page":"2744","DOI":"10.1007\/s43032-021-00699-9","article-title":"Role of Placental Glucose Transporters in Determining Fetal Growth","volume":"29","year":"2022","journal-title":"Reprod Sci"},{"key":"2026070301250527000_2026.06.25.730994v1.6","unstructured":"Yamashita, M. & Markert, U.R . 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