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Published in: Archives of Gynecology and Obstetrics 3/2020

01-03-2020 | Miscarriage | Maternal-Fetal Medicine

H19 regulates angiogenic capacity of extravillous trophoblasts by H19/miR-106a-5p/VEGFA axis

Authors: Hong Zeng, Dongmei He, Hebin Xie, Yuhao Zhao, Zhaoqun Peng, Huan Deng, Jinyue Hu, Binyuan Jiang, Nenghui Liu

Published in: Archives of Gynecology and Obstetrics | Issue 3/2020

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Abstract

Purpose

To investigate the role and underlying mechanism of H19 in regulating angiogenic capacity of extravillous trophoblasts.

Methods

Gain and loss of function experiments were performed using a human first-trimester extravillous trophoblast (EVT) cell line, HTR-8/SVneo cells. H19 was overexpressed or knocked down in HTR-8 cells by transfecting plasmid harboring whole-length H19 sequence (pH19) or siRNA specially targeting H19, respectively (siH19). Cell migration and tube-formation assay were assessed in the indicated groups. Gene expression was detected by RT-qPCR, Western blot, and ELISA assay.

Results

Overexpression of H19 in EVT cells increased cell migration and tube formation, while downregulation of H19 in EVT cells decreased cell migration and tube formation. Furthermore, we found that H19 played its role by VEGFA. In addition, we demonstrated the H19/miR-106a-5p/VEGFA regulatory axis in EVT. Experiments of the clinical specimen showed that H19 was very abundantly expressed in human first-trimester trophoblasts, and we found that the expression of H19 and VEGFA were significantly downregulated in the villous tissues from idiopathic recurrent miscarriage (RM) patients; moreover, the expression of H19 and VEGFA was positively correlated.

Conclusion

H19/miR-106a-5p/VEGFA axis plays a role in regulating the angiogenic capacity of EVT, which might contribute to idiopathic RM.
Literature
1.
go back to reference He D, Zeng H, Chen J et al (2019) H19 regulates trophoblastic spheroid adhesion by competitively binding to let-7. Reprod 157(5):423–430CrossRef He D, Zeng H, Chen J et al (2019) H19 regulates trophoblastic spheroid adhesion by competitively binding to let-7. Reprod 157(5):423–430CrossRef
2.
go back to reference Zuckerwise L, Li J, Lu L et al (2016) H19 long noncoding RNA alters trophoblast cell migration and invasion by regulating TbetaR3 in placentae with fetal growth restriction. Oncotarget 7(25):38398–38407CrossRef Zuckerwise L, Li J, Lu L et al (2016) H19 long noncoding RNA alters trophoblast cell migration and invasion by regulating TbetaR3 in placentae with fetal growth restriction. Oncotarget 7(25):38398–38407CrossRef
3.
go back to reference Torry DS, Leavenworth J, Chang M et al (2007) Angiogenesis in implantation. J Assist Reprod Genet 24(7):303–315CrossRef Torry DS, Leavenworth J, Chang M et al (2007) Angiogenesis in implantation. J Assist Reprod Genet 24(7):303–315CrossRef
4.
go back to reference Wulff C, Weigand M, Kreienberg R et al (2003) Angiogenesis during primate placentation in health and disease. Reproduction 126(5):569–577CrossRef Wulff C, Weigand M, Kreienberg R et al (2003) Angiogenesis during primate placentation in health and disease. Reproduction 126(5):569–577CrossRef
5.
go back to reference Bischof P, Irminger-Finger I (2005) The human cytotrophoblastic cell, a mononuclear chameleon. Int J Biochem Cell Biol 37(1):1–16CrossRef Bischof P, Irminger-Finger I (2005) The human cytotrophoblastic cell, a mononuclear chameleon. Int J Biochem Cell Biol 37(1):1–16CrossRef
6.
go back to reference Ishii T, Miyazawa M, Takanashi Y et al (2014) Genetically induced oxidative stress in mice causes thrombocytosis, splenomegaly and placental angiodysplasia that leads to recurrent abortion. Redox Biol 2:679–685CrossRef Ishii T, Miyazawa M, Takanashi Y et al (2014) Genetically induced oxidative stress in mice causes thrombocytosis, splenomegaly and placental angiodysplasia that leads to recurrent abortion. Redox Biol 2:679–685CrossRef
7.
go back to reference Banerjee P, Ghosh S, Dutta M et al (2013) Identification of key contributory factors responsible for vascular dysfunction in idiopathic recurrent spontaneous miscarriage. PLoS ONE 8(11):e80940CrossRef Banerjee P, Ghosh S, Dutta M et al (2013) Identification of key contributory factors responsible for vascular dysfunction in idiopathic recurrent spontaneous miscarriage. PLoS ONE 8(11):e80940CrossRef
8.
go back to reference Zhu Y, Lu H, Huo Z et al (2016) MicroRNA-16 inhibits feto-maternal angiogenesis and causes recurrent spontaneous abortion by targeting vascular endothelial growth factor. Sci Rep 6:35536CrossRef Zhu Y, Lu H, Huo Z et al (2016) MicroRNA-16 inhibits feto-maternal angiogenesis and causes recurrent spontaneous abortion by targeting vascular endothelial growth factor. Sci Rep 6:35536CrossRef
9.
go back to reference Klauber N, Rohan RM, Flynn E et al (1997) Critical components of the female reproductive pathway are suppressed by the angiogenesis inhibitor AGM-1470. Nat Med 3(4):443–446CrossRef Klauber N, Rohan RM, Flynn E et al (1997) Critical components of the female reproductive pathway are suppressed by the angiogenesis inhibitor AGM-1470. Nat Med 3(4):443–446CrossRef
10.
go back to reference Meegdes BH, Ingenhoes R, Peeters LL et al (1988) Early pregnancy wastage: relationship between chorionic vascularization and embryonic development. Fertil Steril 49(2):216–220CrossRef Meegdes BH, Ingenhoes R, Peeters LL et al (1988) Early pregnancy wastage: relationship between chorionic vascularization and embryonic development. Fertil Steril 49(2):216–220CrossRef
11.
go back to reference Zeng H, Fan X, Liu N (2017) Expression of H19 imprinted gene in patients with repeated implantation failure during the window of implantation. Arch Gynecol Obstet 296(4):835–839CrossRef Zeng H, Fan X, Liu N (2017) Expression of H19 imprinted gene in patients with repeated implantation failure during the window of implantation. Arch Gynecol Obstet 296(4):835–839CrossRef
12.
go back to reference Poirier F, Chan CT, Timmons PM et al (1991) The murine H19 gene is activated during embryonic stem cell differentiation in vitro and at the time of implantation in the developing embryo. Development 113(4):1105–1114PubMed Poirier F, Chan CT, Timmons PM et al (1991) The murine H19 gene is activated during embryonic stem cell differentiation in vitro and at the time of implantation in the developing embryo. Development 113(4):1105–1114PubMed
13.
go back to reference Xu J, Xia Y, Zhang H et al (2018) Overexpression of long non-coding RNA H19 promotes invasion and autophagy via the PI3K/AKT/mTOR pathways in trophoblast cells. Biomed Pharmacother 101:691–697CrossRef Xu J, Xia Y, Zhang H et al (2018) Overexpression of long non-coding RNA H19 promotes invasion and autophagy via the PI3K/AKT/mTOR pathways in trophoblast cells. Biomed Pharmacother 101:691–697CrossRef
14.
go back to reference Jauniaux E, Poston L, Burton GJ (2006) Placental-related diseases of pregnancy: involvement of oxidative stress and implications in human evolution. Hum Reprod Update 12(6):747–755CrossRef Jauniaux E, Poston L, Burton GJ (2006) Placental-related diseases of pregnancy: involvement of oxidative stress and implications in human evolution. Hum Reprod Update 12(6):747–755CrossRef
15.
go back to reference Voellenkle C, Garcia-Manteiga JM, Pedrotti S et al (2016) Implication of long noncoding RNAs in the endothelial cell response to hypoxia revealed by RNA-sequencing. Sci Rep 6(1):24141CrossRef Voellenkle C, Garcia-Manteiga JM, Pedrotti S et al (2016) Implication of long noncoding RNAs in the endothelial cell response to hypoxia revealed by RNA-sequencing. Sci Rep 6(1):24141CrossRef
16.
go back to reference Hou J, Wang L, Wu Q et al (2018) Long noncoding RNA H19 upregulates vascular endothelial growth factor A to enhance mesenchymal stem cells survival and angiogenic capacity by inhibiting miR-199a-5p. Stem Cell Res Ther 9(1):109CrossRef Hou J, Wang L, Wu Q et al (2018) Long noncoding RNA H19 upregulates vascular endothelial growth factor A to enhance mesenchymal stem cells survival and angiogenic capacity by inhibiting miR-199a-5p. Stem Cell Res Ther 9(1):109CrossRef
17.
go back to reference Zhang C, Li Q, Ren N et al (2015) Placental miR-106a~363 cluster is dysregulated in preeclamptic placenta. Placenta 36(2):250–252CrossRef Zhang C, Li Q, Ren N et al (2015) Placental miR-106a~363 cluster is dysregulated in preeclamptic placenta. Placenta 36(2):250–252CrossRef
18.
go back to reference Premlata K, Yanmin L, Carmen T et al (2013) The c-Myc-regulated microRNA-17~92 (miR-17~92) and miR-106a~363 clusters target hCYP19A1 and hGCM1 to inhibit human trophoblast differentiation. Mol Cell Biol 33(9):1782–1796CrossRef Premlata K, Yanmin L, Carmen T et al (2013) The c-Myc-regulated microRNA-17~92 (miR-17~92) and miR-106a~363 clusters target hCYP19A1 and hGCM1 to inhibit human trophoblast differentiation. Mol Cell Biol 33(9):1782–1796CrossRef
19.
go back to reference Fang Y, Yu S, Ma Y et al (2013) Association of Dll4/notch and HIF-1a-VEGF signaling in the angiogenesis of missed abortion. PLoS ONE 8(8):e70667CrossRef Fang Y, Yu S, Ma Y et al (2013) Association of Dll4/notch and HIF-1a-VEGF signaling in the angiogenesis of missed abortion. PLoS ONE 8(8):e70667CrossRef
20.
go back to reference Meher A, Sundrani D, Joshi S (2015) Maternal nutrition influences angiogenesis in the placenta through peroxisome proliferator activated receptors: a novel hypothesis. Mol Reprod Dev 82(10):726–734CrossRef Meher A, Sundrani D, Joshi S (2015) Maternal nutrition influences angiogenesis in the placenta through peroxisome proliferator activated receptors: a novel hypothesis. Mol Reprod Dev 82(10):726–734CrossRef
21.
go back to reference De Falco S (2012) The discovery of placenta growth factor and its biological activity. Exp Mol Med 44(1):1–9CrossRef De Falco S (2012) The discovery of placenta growth factor and its biological activity. Exp Mol Med 44(1):1–9CrossRef
22.
go back to reference Hiratsuka S, Kataoka Y, Nakao K et al (2005) Vascular endothelial growth factor A (VEGF-A) is involved in guidance of VEGF receptor-positive cells to the anterior portion of early embryos. Mol Cell Biol 25(1):355–363CrossRef Hiratsuka S, Kataoka Y, Nakao K et al (2005) Vascular endothelial growth factor A (VEGF-A) is involved in guidance of VEGF receptor-positive cells to the anterior portion of early embryos. Mol Cell Biol 25(1):355–363CrossRef
23.
go back to reference Ferrara N (2004) Vascular endothelial growth factor: basic science and clinical progress. Endocr Rev 25(4):581–611CrossRef Ferrara N (2004) Vascular endothelial growth factor: basic science and clinical progress. Endocr Rev 25(4):581–611CrossRef
24.
go back to reference Amirchaghmaghi E, Rezaei A, Moini A et al (2015) Gene expression analysis of VEGF and its receptors and assessment of its serum level in unexplained recurrent spontaneous abortion. Cell J 16(4):538–545PubMedPubMedCentral Amirchaghmaghi E, Rezaei A, Moini A et al (2015) Gene expression analysis of VEGF and its receptors and assessment of its serum level in unexplained recurrent spontaneous abortion. Cell J 16(4):538–545PubMedPubMedCentral
25.
go back to reference Kutluer G, Cicek NM, Moraloglu O et al (2012) Low VEGF expression in conceptus material and maternal serum AFP and beta-hCG levels as indicators of defective angiogenesis in first-trimester miscarriages. J Turk Ger Gynecol Assoc 13(2):111–117PubMedPubMedCentral Kutluer G, Cicek NM, Moraloglu O et al (2012) Low VEGF expression in conceptus material and maternal serum AFP and beta-hCG levels as indicators of defective angiogenesis in first-trimester miscarriages. J Turk Ger Gynecol Assoc 13(2):111–117PubMedPubMedCentral
26.
go back to reference Bagheri A, Kumar P, Kamath A et al (2017) Association of angiogenic cytokines (VEGF-A and VEGF-C) and clinical characteristic in women with unexplained recurrent miscarriage. Bratisl Lek Listy 118(5):258–264PubMed Bagheri A, Kumar P, Kamath A et al (2017) Association of angiogenic cytokines (VEGF-A and VEGF-C) and clinical characteristic in women with unexplained recurrent miscarriage. Bratisl Lek Listy 118(5):258–264PubMed
27.
go back to reference Plaisier M, Dennert I, Rost E et al (2009) Decidual vascularization and the expression of angiogenic growth factors and proteases in first trimester spontaneous abortions. Hum Reprod 24(1):185–197CrossRef Plaisier M, Dennert I, Rost E et al (2009) Decidual vascularization and the expression of angiogenic growth factors and proteases in first trimester spontaneous abortions. Hum Reprod 24(1):185–197CrossRef
28.
go back to reference Vuorela P, Carpen O, Tulppala M et al (2000) VEGF, its receptors and the tie receptors in recurrent miscarriage. Mol Hum Reprod 6(3):276–282CrossRef Vuorela P, Carpen O, Tulppala M et al (2000) VEGF, its receptors and the tie receptors in recurrent miscarriage. Mol Hum Reprod 6(3):276–282CrossRef
29.
go back to reference Almawi WY, Saldanha FL, Mahmood NA et al (2013) Relationship between VEGFA polymorphisms and serum VEGF protein levels and recurrent spontaneous miscarriage. Hum Reprod 28(10):2628–2635CrossRef Almawi WY, Saldanha FL, Mahmood NA et al (2013) Relationship between VEGFA polymorphisms and serum VEGF protein levels and recurrent spontaneous miscarriage. Hum Reprod 28(10):2628–2635CrossRef
Metadata
Title
H19 regulates angiogenic capacity of extravillous trophoblasts by H19/miR-106a-5p/VEGFA axis
Authors
Hong Zeng
Dongmei He
Hebin Xie
Yuhao Zhao
Zhaoqun Peng
Huan Deng
Jinyue Hu
Binyuan Jiang
Nenghui Liu
Publication date
01-03-2020
Publisher
Springer Berlin Heidelberg
Keyword
Miscarriage
Published in
Archives of Gynecology and Obstetrics / Issue 3/2020
Print ISSN: 0932-0067
Electronic ISSN: 1432-0711
DOI
https://doi.org/10.1007/s00404-020-05469-7

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