Skip to main content

Advertisement

SpringerLink
Log in

Effect of Placental Growth Factor on Trophoblast–Endothelial Cell Interactions In Vitro

  • Original Article
  • Published:
Reproductive Sciences Aims and scope Submit manuscript

Abstract

Placental growth factor (PlGF) is an important angiogenic factor which has an emerging role in the clinical management of suspected preeclampsia. The role of PlGF in normal placental development is not completely understood and it is uncertain whether PlGF influences trophoblast and endothelial cell interactions central to uterine spiral artery remodelling, especially in variable oxygen conditions. A two-cell model of endovascular invasion was used. Tissue culture plates were coated with Matrigel™, on which fluorescent-labelled uterine microvascular endothelial cells (1 × 105/well) and HTR8/SVNeo cells were co-cultured (1 × 105/well) for 20 h. Co-cultures were treated with recombinant human PlGF (rhPlGF) (10 or 100 ng/mL) and incubated at either 21% O2 or 2% O2. Images were captured by fluorescence microscopy and analysed using ImageJ (n = 7). Data was analysed using SPSSv24. Treatment with rhPlGF did not improve integration in co-cultures irrespective of oxygen conditions but increased proliferation in 2% O2 of both trophoblast and endothelial cells. Expression of angiogenic factors VEGF, sFLT-1, PlGF and CXCL12 in both co-cultures and in isolated trophoblast cells was not altered by rhPlGF treatment. Expression of TLR-3 mRNA in co-cultures was increased by rhPlGF 100 ng/mL at 21% O2 (p = 0.03). PlGF contributes to trophoblast and endothelial cell proliferation in the setting of physiological hypoxia but does not influence trophoblast and endothelial cell interactions in an in vitro model of spiral artery remodelling. Upregulation of TLR-3 expression in co-cultures may indicate a role for PlGF in the placental inflammatory response.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Arroyo J, Price M, Straszewski-Chavez S, Torry RJ, Mor G, Torry DS. XIAP protein is induced by placenta growth factor (PLGF) and decreased during preeclampsia in trophoblast cells. Syst Biol Reprod Med. 2014;60(5):263–73.

    Article  CAS  PubMed  Google Scholar 

  2. Chappell LC, Duckworth S, Seed PT, Griffin M, Myers J, Mackillop L, et al. Diagnostic accuracy of placental growth factor in women with suspected preeclampsia: a prospective multicenter study. Circulation. 2013;128(19):2121–31.

    Article  CAS  PubMed  Google Scholar 

  3. Duhig KE, Myers J, Seed PT, Sparkes J, Lowe J, Hunter RM, et al. Placental growth factor testing to assess women with suspected pre-eclampsia: a multicentre, pragmatic, stepped-wedge cluster-randomised controlled trial. Lancet. 2019;393(10183):1807–18.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Torry DS, Mukherjea D, Arroyo J, Torry RJ. Expression and function of placenta growth factor: implications for abnormal placentation. J Soc Gynecol Investig. 2003;10(4):178–88.

    Article  CAS  PubMed  Google Scholar 

  5. Chau K, Hennessy A, Makris A. Placental growth factor and pre-eclampsia. J Hum Hypertens. 2017;31:782.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Carmeliet P, Moons L, Luttun A, Vincenti V, Compernolle V, de Mol M, et al. Synergism between vascular endothelial growth factor and placental growth factor contributes to angiogenesis and plasma extravasation in pathological conditions. Nat Med. 2001;7(5):575–83.

    Article  CAS  PubMed  Google Scholar 

  7. Ratsep MT, Carmeliet P, Adams MA, Croy BA. Impact of placental growth factor deficiency on early mouse implant site angiogenesis. Placenta. 2014;35(9):772–5.

    Article  CAS  PubMed  Google Scholar 

  8. Ahmed A, Dunk C, Ahmad S, Khaliq A. Regulation of placental vascular endothelial growth factor (VEGF) and placenta growth factor (PIGF) and soluble Flt-1 by oxygen--a review. Placenta. 2000;21(Suppl A):S16–24.

    Article  PubMed  Google Scholar 

  9. Athanassiades A, Lala PK. Role of placenta growth factor (PIGF) in human extravillous trophoblast proliferation, migration and invasiveness. Placenta. 1998;19(7):465–73.

    Article  CAS  PubMed  Google Scholar 

  10. Knuth A, Liu L, Nielsen H, Merril D, Torry DS, Arroyo JA. Placenta growth factor induces invasion and activates p70 during rapamycin treatment in trophoblast cells. Am J Reprod Immunol. 2015;73(4):330–40.

    Article  CAS  PubMed  Google Scholar 

  11. Lash GE, Cartwright JE, Whitley GS, Trew AJ, Baker PN. The effects of angiogenic growth factors on extravillous trophoblast invasion and motility. Placenta. 1999;20(8):661–7.

    Article  CAS  PubMed  Google Scholar 

  12. Gobble RM, Groesch KA, Chang M, Torry RJ, Torry DS. Differential regulation of human PlGF gene expression in trophoblast and nontrophoblast cells by oxygen tension. Placenta. 2009;30(10):869–75.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Wang L, Li X, Zhao Y, Fang C, Lian Y, Gou W, et al. Insights into the mechanism of CXCL12-mediated signaling in trophoblast functions and placental angiogenesis. Acta Biochim Biophys Sin. 2015;47(9):663–72.

    Article  CAS  PubMed  Google Scholar 

  14. Zhou WH, Du MR, Dong L, Yu J, Li DJ. Chemokine CXCL12 promotes the cross-talk between trophoblasts and decidual stromal cells in human first-trimester pregnancy. Hum Reprod. 2008;23(12):2669–79.

    Article  CAS  PubMed  Google Scholar 

  15. Quinn KE, Ashley AK, Reynolds LP, Grazul-Bilska AT, Ashley RL. Activation of the CXCL12/CXCR4 signaling axis may drive vascularization of the ovine placenta. Domest Anim Endocrinol. 2014;47:11–21.

    Article  CAS  PubMed  Google Scholar 

  16. Lei GQ, Wu ZY, Jiang WB, et al. Effect of CXCL12/CXCR4 on migration of decidua-derived mesenchymal stem cells from pregnancies with preeclampsia. Am J Reprod Immunol. 2019:e13180.

  17. Hanna J, Wald O, Goldman-Wohl D, et al. CXCL12 expression by invasive trophoblasts induces the specific migration of CD16- human natural killer cells. Blood. 2003;102(5):1569–77.

    Article  CAS  PubMed  Google Scholar 

  18. Mor G, Romero R, Aldo PB, Abrahams VM. Is the trophoblast an immune regulator? The role of toll-like receptors during pregnancy. Crit Rev Immunol. 2005;25(5):375–88.

    Article  CAS  PubMed  Google Scholar 

  19. Zhao R, Zhang J, Wang Y, et al. Activation of toll-like receptor 3 promotes pathological corneal neovascularization by enhancement of SDF-1-mediated endothelial progenitor cell recruitment. Exp Eye Res. 2019;178:177–85.

    Article  CAS  PubMed  Google Scholar 

  20. Aldo PB, Krikun G, Visintin I, Lockwood C, Romero R, Mor G. A novel three-dimensional in vitro system to study trophoblast-endothelium cell interactions. Am J Reprod Immunol. 2007;58(2):98–110.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Jauniaux E, Watson AL, Hempstock J, Bao YP, Skepper JN, Burton GJ. Onset of maternal arterial blood flow and placental oxidative stress. A possible factor in human early pregnancy failure. Am J Pathol. 2000;157(6):2111–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Hannan NJ, Paiva P, Dimitriadis E, Salamonsen LA. Models for study of human embryo implantation: choice of cell lines? Biol Reprod. 2010;82(2):235–45.

    Article  CAS  PubMed  Google Scholar 

  23. Xu B, Charlton F, Makris A, Hennessy A. Antihypertensive drugs methyldopa, labetalol, hydralazine, and clonidine improve trophoblast interaction with endothelial cellular networks in vitro. J Hypertens. 2014;32(5):1075–83 discussion 1083.

    Article  CAS  PubMed  Google Scholar 

  24. Jauniaux E, Watson A, Ozturk O, Quick D, Burton G. In-vivo measurement of intrauterine gases and acid-base values early in human pregnancy. Hum Reprod. 1999;14(11):2901–4.

    Article  CAS  PubMed  Google Scholar 

  25. Desai J, Holt-Shore V, Torry RJ, Caudle MR, Torry DS. Signal transduction and biological function of placenta growth factor in primary human trophoblast. Biol Reprod. 1999;60(4):887–92.

    Article  CAS  PubMed  Google Scholar 

  26. Tarrade A, Goffin F, Munaut C, Lai-Kuen R, Tricottet V, Foidart JM, et al. Effect of matrigel on human extravillous trophoblasts differentiation: modulation of protease pattern gene expression. Biol Reprod. 2002;67(5):1628–37.

    Article  CAS  PubMed  Google Scholar 

  27. Highet AR, Zhang VJ, Heinemann GK, Roberts CT. Use of Matrigel in culture affects cell phenotype and gene expression in the first trimester trophoblast cell line HTR8/SVneo. Placenta. 2012;33(7):586–8.

    Article  CAS  PubMed  Google Scholar 

  28. Xu B, Shanmugalingam R, Chau K, Pears S, Hennessy A, Makris A. The effect of acetyl salicylic acid (aspirin) on trophoblast-endothelial interaction in vitro. J Reprod Immunol. 2017;124:54–61.

    Article  CAS  PubMed  Google Scholar 

  29. Munaut C, Lorquet S, Pequeux C, Blacher S, Berndt S, Frankenne F, et al. Hypoxia is responsible for soluble vascular endothelial growth factor receptor-1 (VEGFR-1) but not for soluble endoglin induction in villous trophoblast. Hum Reprod. 2008;23(6):1407–15.

    Article  CAS  PubMed  Google Scholar 

  30. Powers RW, Roberts JM, Plymire DA, Pucci D, Datwyler SA, Laird DM, et al. Low placental growth factor across pregnancy identifies a subset of women with preterm preeclampsia: type 1 versus type 2 preeclampsia? Hypertension. 2012;60(1):239–46.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Andraweera PH, Dekker GA, Laurence JA, Roberts CT. Placental expression of VEGF family mRNA in adverse pregnancy outcomes. Placenta. 2012;33(6):467–72.

    Article  CAS  PubMed  Google Scholar 

  32. Maebayashi Asanuma A, Yamamoto T, Azuma H, Kato E, Yamamoto N, Murase T, et al. Expression of placenta growth factor, soluble fms-like tyrosine kinase-1, metal-responsive transcription factor-1, heme oxygenase 1 and hypoxia inducible factor-1alpha mRNAs in pre-eclampsia placenta and the effect of pre-eclampsia sera on their expression of choriocarcinoma cells. J Obstet Gynaecol Res. 2014;40(10):2095–103.

    Article  PubMed  Google Scholar 

  33. Genbacev O, Zhou Y, Ludlow JW, Fisher SJ. Regulation of human placental development by oxygen tension. Science. 1997;277(5332):1669–72.

    Article  CAS  PubMed  Google Scholar 

  34. Pijnenborg R, Vercruysse L, Hanssens M. The uterine spiral arteries in human pregnancy: facts and controversies. Placenta. 2006;27(9–10):939–58.

    Article  CAS  PubMed  Google Scholar 

  35. Falco ML, Sivanathan J, Laoreti A, Thilaganathan B, Khalil A. Placental histopathology associated with pre-eclampsia: systematic review and meta-analysis. Ultrasound Obstet Gynecol. 2017;50(3):295–301.

    Article  CAS  PubMed  Google Scholar 

  36. Ogge G, Chaiworapongsa T, Romero R, Hussein Y, Kusanovic JP, Yeo L, et al. Placental lesions associated with maternal underperfusion are more frequent in early-onset than in late-onset preeclampsia. J Perinat Med. 2011;39(6):641–52.

    Article  PubMed  PubMed Central  Google Scholar 

  37. Kang MC, Park SJ, Kim HJ, et al. Gestational loss and growth restriction by angiogenic defects in placental growth factor transgenic mice. Arterioscler Thromb Vasc Biol. 2014;34(10):2276–82.

    Article  CAS  PubMed  Google Scholar 

  38. Ishida I, Kubo H, Suzuki S, et al. Hypoxia diminishes toll-like receptor 4 expression through reactive oxygen species generated by mitochondria in endothelial cells. J Immunol. 2002;169(4):2069–75.

    Article  CAS  PubMed  Google Scholar 

  39. Kato E, Yamamoto T, Chishima F. Effects of cytokines and TLR ligands on the production of PlGF and sVEGFR1 in primary Trophoblasts. Gynecol Obstet Investig. 2017;82(1):39–46.

    Article  CAS  Google Scholar 

  40. Pringle KG, Kind KL, Sferruzzi-Perri AN, Thompson JG, Roberts CT. Beyond oxygen: complex regulation and activity of hypoxia inducible factors in pregnancy. Hum Reprod Update. 2010;16(4):415–31.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Vascular Immunology Group, Heart Research Institute, Sydney, Australia

    K. Chau, B. Xu, A. Hennessy & A. Makris

  2. School of Medicine, Western Sydney University, Sydney, Australia

    K. Chau, A. Hennessy & A. Makris

  3. Regional Dialysis Centre, Blacktown Hospital, Blacktown, Australia

    K. Chau

  4. Renal Department, Liverpool Hospital, Liverpool, Australia

    A. Makris

Authors
  1. K. Chau
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. B. Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. A. Hennessy
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. A. Makris
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to K. Chau.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Chau, K., Xu, B., Hennessy, A. et al. Effect of Placental Growth Factor on Trophoblast–Endothelial Cell Interactions In Vitro. Reprod. Sci. 27, 1285–1292 (2020). https://doi.org/10.1007/s43032-019-00103-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s43032-019-00103-7

Keywords

Search

Navigation