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PLoS One. 2013 Oct 15;8(10):e77340. doi: 10.1371/journal.pone.0077340. eCollection 2013.

Global expression of molecular transporters in the human vaginal tract: implications for HIV chemoprophylaxis.

Author information

1
Department of Chemistry, Oak Crest Institute of Science, Pasadena, California, United States of America.

Abstract

BACKGROUND:

Pre-exposure chemoprophylaxis (PrECP) using antiretroviral agents is a promising strategy for the prevention of sexual HIV transmission in women. Molecular transporters in the human vaginal tract (VT) may play a pivotal role in determining drug disposition and, consequently, pharmacodynamic outcomes in these efforts. Little is known, however, on the expression of these transporters in vaginal tissues, representing a critical knowledge gap.

METHODOLOGY/PRINCIPAL FINDINGS:

Our study analyzed the genome-wide transcriptome in 44 vaginal tissue samples from 6 reproductive-age women undergoing gynecologic surgeries. The analysis revealed that, unexpectedly, a large number (43%) of gene isoforms corresponding to membrane transporters were over-expressed (above the median expression level) in all samples. A subset of 12 highly expressed membrane transporters was identified and contained 10 members (83%) of the solute carrier superfamily. The largest difference in membrane transporter gene expression was observed across subjects, but more subtle differential expression also was found along the anterior-posterior axis of the VT. Cross-validation of the microarray analyses with measurements RT-qPCR demonstrated high concordance between these data sets. Immunofluorescence labeling of membrane transporter proteins in vaginal tissues was highly dependent on tissue/cell types.

CONCLUSIONS/SIGNIFICANCE:

Antiretroviral PrECP drugs currently under evaluation are substrates for molecular transporters that were commonly expressed, but fell into both over- or under-expressed categories in all samples, suggesting a complex role for carrier-mediated processes in determining the disposition of these xenobiotics in vaginal tissues. These findings hold important implications for the successful development of products, either oral or intravaginal, for female-controlled HIV PrECP.

PMID:
24143220
PMCID:
PMC3797116
DOI:
10.1371/journal.pone.0077340
[Indexed for MEDLINE]
Free PMC Article

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