Reproductive toxicology (Elmsford, N.Y.) · 2025
Deep RNA analyses for BeWo cells and placentae of HIV positive pregnant women treated with lopinavir/ritonavir.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Zou Shi, Guo Wei, Tan Miao, Yu Xuechen, Liu Jinli, Du Qian, Tan Yuting, Wu Yingjie, Wu Songjie, Zhu Yanan, Feng Yong, Liang Ke
Аннотация
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.
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.