Deep RNA analyses for BeWo cells and placentae of HIV positive pregnant women treated with lopinavir/ritonavir.

INTRODUCTION

Combination antiretroviral therapy (cART) based on protease inhibitor lopinavir /ritonavir (LPV/r) is the first-line regimen for HIV-infected pregnant women to prevent mother-to-child transmission (MTCT) in China. Studies have indicated a correlation between LPV/r and adverse pregnancy outcomes (APOs). However, a knowledge gap exists regarding the potential mechanisms.

METHODS

In this study, the transcriptomics and proteomics analyses were performed to investigate the genes in BeWo cells and human placentae exposed to LPV/r. BeWo cells were treated with LPV/r with different concentrations for 24 h, then the mRNAs were sequenced. We also adopted proteomics sequencing between human placentae exposed to LPV/r and non-LPV/r based antiretroviral regimens. Flow cytometry analysis, real-time PCR and immunohistochemistry were performed to verified our sequencing results.

RESULTS

A Total 800-4000 differentially expressed genes (DEGs) after LPV/r treatment in Bewo cells were identified compared to the vehicle control. There were 321 differentially expressed proteins (DEPs) in the LPV/r group of human placentae. Comprehensive analysis of the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) terms in transcriptomics and proteomics analyses demonstrated that LPV/r may result in APOs via active apoptosis, Endoplasmic reticulum (ER) stress, oxidative stress and lipid metabolism. Expression up-regulation of BAX (Bcl2 Associated X Protein), C-FOS (Cellular oncogene fos), P53 (Tumor suppressor protein p53) and down- regulation of MDM2 (Mouse double minute 2 homolog) by LPV/r may be the key genes for APOs.

CONCLUSIONS

Apoptosis by LPV/r may be the most important factor for APOs. The deep analysis provides important clues for understanding the mechanisms for the APOs were attributed to LPV/r.