Transcriptomic Profiling of SLC and ABC Transporters in the Human Term Placenta

Abstract

Solute carriers (SLC) and ATP-binding cassette (ABC) transporters are essential for placental solute exchange and fetal protection, yet their transcriptomic profiles in the human placenta remain poorly characterized. Moreover, although fetal sex influences placental development and function, its impact on transporter expression is yet to be determined. Using RNA sequencing, we profiled SLC and ABC transporter expression in two anatomical regions of healthy term human placentas with balanced fetal sex representation. In the intervillous region, 276 SLCs were detected, with the majority (60%) expressed at low levels (CPM < 25). The remaining 110 SLCs (40%) were expressed at higher levels (CPM 25–1650). Four transporters—SLC2A1 (GLUT1), SLC44A2 (CTL2), SLC38A2 (SNAT2), and SLC38A1 (SNAT1)—showed the highest expression (CPM > 500). Functional annotation of the top 110 SLCs revealed that transporters for metals, amino acids, and inorganic ions with each respectively accounting for 9% of the 110 annotated SLC genes. Other well-represented SLCs included xenobiotic, vitamin, sugar, and neurotransmitter transporters. Mitochondrial, lysosomal, and ER/Golgi transporters together accounted for approximately 37%, while 11% were orphan transporters with no known substrates. Thirty-seven ABC transcripts were detected in the intervillous region, primarily involved in xenobiotic and lipid transport. Compared with the intervillous region, 1,676 genes—including 32 SLCs and 2 ABC transporters—were differentially expressed in the decidual region. Although 79 genes in the intervillous region and 117 genes in the decidual region exhibited sexually dimorphic expression, none were SLC transporters. Notably, placentas from male fetuses showed significantly higher expression of ABCB2 (P-gp), a finding further confirmed by qPCR and western blot analysis. Together, these findings provide a comprehensive transcriptomic map of SLC and ABC transporters in the term human placenta and suggested potential impact of fetal sex on ABCB2 and xenobiotic protection.