Whole genome miRNA profiling revealed miR-199a as potential placental pathogenesis of selective fetal growth restriction in monochorionic twin pregnancies
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AbstractIntroduction Placental-related mechanism of fetal growth restriction (FGR) is still unknown. Here we aimed to profile whole-genome miRNA between selective FGR twin (sFGR-T) and normally larger co-twin (sL-T) in monochorionic (MC) twin pregnancies and to further investigate effect of the miRNA on placental pathogenesis, including angiogenesis and mitochondrial functions. Methods MC twin pregnancies with or without sFGR were recruited, and their placental miRNAs were profiled (n = 3 vs 5). Ratio of placental miRNAs in the sFGR twin pairs (sFGR-T/sL-T) were calculated and compared to that in the control twin pairs (cS-T/cL-T). Differentially expressed miRNAs and associated markers were validated qRT-PCR, immunohistochemistry staining (n = 8 vs 13) and electron microscopy (n = 3 vs 3). Results Placental miR-199a-5p was significantly upregulated in sFGR-T (p = 0.004), which was validated by qRT-PCR (1.03 vs 0.56; p = 0.020). Compared to control twin pairs, ratio of CD31-positive vessels and volume density of vessels in sFGR twin pairs was lower (0.65 vs 0.92 and 18.7% vs 36.3%; both p < 0.001), while that of cyclooxygenase 2 (COX2)-positive trophoblast cells was higher (3.50 vs 2.22; p = 0.001), indicating an impaired angiogenesis and oxidative stress in the sFGR placenta. In addition, ratio of mitochondrial DNA (mtDNA) mitochondrial encoded NADH dehydrogenase 1 (MTND1) copy numbers (2.10 vs 0.90; p = 0.013), H-score ratios of mitochondrial markers citrate synthase (CS) and cytochrome c oxidase subunit 4 isoform 1 (COX4, 0.53 vs 0.95, p < 0.001; 0.29 vs 1.06, p < 0.001) in trophoblast cells of sFGR twin pairs were also altered significantly and correlated with angiogenesis. Furthermore, ratio of mitochondrial numbers per trophoblasts (8.67 vs 18.67; p = 0.006) and percentage of swollen mitochondria (84.33 vs 11.33; p = 0.003) were converted significantly, indicating mitochondrial damage. Discussion Our results suggested miR-199a-5p may play a role in the placental angiogenesis, oxidative stress and mitochondrial damage and dysfunction as an underlying pathogenesis of sFGR.
Acceptance Date03/02/2020
All Author(s) ListMeng Meng, Cheng Yvonne Kwun Yue, Wu Ling, Chaemsaithong Piya, Leung Maran Bo Wah, Chim Stephen Siu Chung, Sahota Daljit Singh, Li Wei, Poon Liona Chiu Yee, Wang Chi Chiu, Leung Tak Yeung
Journal namePlacenta
Volume Number92
Pages44 - 53
LanguagesEnglish-United Kingdom
KeywordsMC twins, sFGR, miR-199a-5p, Oxidative stress, Mitochondria

Last updated on 2021-20-06 at 00:18