Meng Meng1, Yvonne Kwun Yue Cheng2, Ling Wu3, Piya Chaemsaithong4, Maran Bo Wah Leung5, Stephen Siu Chung Chim6, Daljit Singh Sahota7, Wei Li8, Liona Chiu Yee Poon9, Chi Chiu Wang10, Tak Yeung Leung11. 1. Department of Obstetrics and Gynaecology, Faculty of Medicine, the Chinese University of Hong Kong, Shatin, Hong Kong. Electronic address: mengmengmumu@gmail.com. 2. Department of Obstetrics and Gynaecology, Faculty of Medicine, the Chinese University of Hong Kong, Shatin, Hong Kong. Electronic address: yvonnecheng@cuhk.edu.hk. 3. Department of Obstetrics and Gynaecology, Faculty of Medicine, the Chinese University of Hong Kong, Shatin, Hong Kong. Electronic address: linda_wu@cuhk.edu.hk. 4. Department of Obstetrics and Gynaecology, Faculty of Medicine, the Chinese University of Hong Kong, Shatin, Hong Kong. Electronic address: piyachaemsaithong@cuhk.edu.hk. 5. Department of Obstetrics and Gynaecology, Faculty of Medicine, the Chinese University of Hong Kong, Shatin, Hong Kong. Electronic address: maranleung@cuhk.edu.hk. 6. Department of Obstetrics and Gynaecology, Faculty of Medicine, the Chinese University of Hong Kong, Shatin, Hong Kong. Electronic address: sschim@cuhk.edu.hk. 7. Department of Obstetrics and Gynaecology, Faculty of Medicine, the Chinese University of Hong Kong, Shatin, Hong Kong. Electronic address: daljit@cuhk.edu.hk. 8. Department of Obstetrics and Gynaecology, Faculty of Medicine, the Chinese University of Hong Kong, Shatin, Hong Kong. Electronic address: liwei@link.cuhk.edu.hk. 9. Department of Obstetrics and Gynaecology, Faculty of Medicine, the Chinese University of Hong Kong, Shatin, Hong Kong. Electronic address: liona.poon@cuhk.edu.hk. 10. Department of Obstetrics and Gynaecology, Faculty of Medicine, the Chinese University of Hong Kong, Shatin, Hong Kong; Reproduction and Development, Li Ka Shing Institute of Health Sciences, the Chinese University of Hong Kong, Shatin, Hong Kong; School of Biomedical Sciences, the Chinese University of Hong Kong, Shatin, Hong Kong. Electronic address: ccwang@cuhk.edu.hk. 11. Department of Obstetrics and Gynaecology, Faculty of Medicine, the Chinese University of Hong Kong, Shatin, Hong Kong. Electronic address: tyleung@cuhk.edu.hk.
Abstract
INTRODUCTION: 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.
INTRODUCTION: 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.
Authors: Jesse M Tehrani; Elizabeth Kennedy; Pei Wen Tung; Amber Burt; Karen Hermetz; Tracy Punshon; Brian P Jackson; Ke Hao; Jia Chen; Margaret R Karagas; Devin C Koestler; Barry Lester; Carmen J Marsit Journal: Pediatr Res Date: 2022-07-29 Impact factor: 3.953
Authors: Elizabeth M Kennedy; Karen Hermetz; Amber Burt; Todd M Everson; Maya Deyssenroth; Ke Hao; Jia Chen; Margaret R Karagas; Dong Pei; Devin C Koestler; Carmen J Marsit Journal: Epigenetics Date: 2020-10-04 Impact factor: 4.528