Oxidative Stress Alters miRNA and Gene Expression Profiles in Villous First Trimester Trophoblasts.
The relationship between oxidative stress and miRNA changes in placenta as a potential mechanism involved in preeclampsia (PE) is not fully elucidated. We investigated the impact of oxidative stress on miRNAs and mRNA expression profiles of genes associated with PE in villous 3A first trimester trophoblast cells exposed to H2O2 at 12 different concentrations (0-1 mM) for 0.5, 4, 24, and 48 h. Cytotoxicity, determined using the SRB assay, was used to calculate the IC50 of H2O2. RNA was extracted after 4 h exposure to H2O2 for miRNA and gene expression profiling. H2O2 exerted a concentration- and time-dependent cytotoxicity on 3A trophoblast cells. Short-term exposure of 3A cells to low concentration of H2O2 (5% of IC50) significantly altered miRNA profile as evidenced by significant changes in 195 out of 595 evaluable miRNAs. Tool for annotations of microRNAs (TAM) analysis indicated that these altered miRNAs fall into 43 clusters and 34 families, with 41 functions identified. Exposure to H2O2 altered mRNA expression of 22 out of 84 key genes involved in dysregulation of placental development. In conclusion, short-term exposure of villous first trimester trophoblasts to low concentrations of H2O2 significantly alters miRNA profile and expression of genes implicated in placental development.
Department of Obstetrics and Gynecology, The University of Texas Medical Branch, Galveston, TX 77555-1066, USA.
Courtney E
CE
Cross
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Ain Shams University, Cairo 11566, Egypt.
Mai F
MF
Tolba
Department of Obstetrics and Gynecology, The University of Texas Medical Branch, Galveston, TX 77555-1066, USA.
Catherine M
CM
Rondelli
Department of Obstetrics and Gynecology, The University of Texas Medical Branch, Galveston, TX 77555-1066, USA.
Meixiang
M
Xu
Department of Obstetrics and Gynecology, The University of Texas Medical Branch, Galveston, TX 77555-1066, USA.
Sherif Z
SZ
Abdel-Rahman
D002824:Chorionic Villi / Q000378:metabolism; D005260:Female; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity; D035683:MicroRNAs / Q000096:biosynthesis*; D018384:Oxidative Stress / Q000187:drug effects / Q000235:genetics*; D010920:Placenta / Q000187:drug effects; D010929:Placentation / Q000187:drug effects / Q000235:genetics*; D011225:Pre-Eclampsia / Q000235:genetics* / Q000473:pathology; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D059467:Transcriptome; D014327:Trophoblasts / Q000378:metabolism
D035683:MicroRNAs; D006861:Hydrogen Peroxide