Skip to main content

Advertisement

SpringerLink
Log in

Arachidonic Acid Reverses Xanthohumol-Induced Insufficiency in a Human First-Trimester Extravillous Trophoblast Cell Line (HTR-8/SVneo Cells)

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

Abstract

We previously described a negative effect of xanthohumol (XN) upon placentation-related processes. We aimed to better characterize this effect by investigating the effect of XN upon the uptake of arachidonic acid (ARA), a crucial nutrient during pregnancy, by the HTR-8/SVneo human first-trimester extravillous trophoblast cell line and its relationship with the negative effect of XN upon placentation-related processes. Uptake of 14C-ARA (100 nM) was time dependent and inhibited by short-term (26 minutes) or long-term (24 hours) exposure to XN. Xanthohumol (24 hours; 5 μM) behaved as an uncompetitive inhibitor of 14C-ARA uptake; the mammalian target of rapamycin, tyrosine kinases, and c-Jun N-terminal kinases intracellular pathways were involved in this effect; and it markedly reduced long-chain acyl-CoA synthetase 1 messenger RNA levels. Moreover, the effects of XN (24 hours; 5 μM) upon cell proliferation, culture growth, migration, viability, and apoptosis index were prevented by high extracellular ARA but not by the peroxisome proliferator-activated receptor-γ (PPAR-γ) agonist rosiglitazone. We thus conclude that ARA is an essential nutrient regulating cell viability, proliferation, culture growth, migration, and apoptosis of HTR-8/SVneo cells and that the deleterious effects of XN involve inhibition of ARA cellular uptake but appears to be independent of PPAR-γ activation.

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

Similar content being viewed by others

References

  1. James JL, Carter AM, Chamley LW. Human placentation from nidation to 5 weeks of gestation. Part I: what do we know about formative placental development following implantation? Placenta. 2012;33(5):327–334.

    CAS  PubMed  Google Scholar 

  2. Ji L, Brkic J, Liu M, Fu G, Peng C, Wang YL. Placental trophoblast cell differentiation: physiological regulation and pathological relevance to preeclampsia. Mol Aspects Med. 2013;34(5):981–1023.

    CAS  PubMed  Google Scholar 

  3. Dutta-Roy AK. Transport mechanisms for long-chain polyunsaturated fatty acids in the human placenta. Am J Clin Nutr. 2000;71(suppl 1):315S–322S.

    CAS  PubMed  Google Scholar 

  4. Innis SM. Fatty acids and early human development. Early Hum Dev. 2007;83(12):761–766.

    CAS  PubMed  Google Scholar 

  5. Cunningham P, McDermott L. Long chain PUFA transport in human term placenta. J Nutr. 2009;139(4):636–639.

    CAS  PubMed  Google Scholar 

  6. Koletzko B, Lien E, Agostoni C, et al. The roles of long-chain polyunsaturated fatty acids in pregnancy, lactation and infancy: review of current knowledge and consensus recommendations. J Perinat Med. 2008;36(1):5–14.

    CAS  PubMed  Google Scholar 

  7. Lager S, Powell TL. Regulation of nutrient transport across the placenta. J Pregnancy. 2012;2012:179827.

    PubMed  PubMed Central  Google Scholar 

  8. Araujo JR, Ramalho C, Correia-Branco A, et al. A parallel increase in placental oxidative stress and antioxidant defenses occurs in pre-gestational type 1 but not gestational diabetes. Placenta. 2013;34(11):1095–1098.

    CAS  PubMed  Google Scholar 

  9. Tobin KA, Johnsen GM, Staff AC, Duttaroy AK. Long-chain polyunsaturated fatty acid transport across human placental choriocarcinoma (BeWo) cells. Placenta. 2009;30(1):41–47.

    CAS  PubMed  Google Scholar 

  10. Basak S, Das MK, Duttaroy AK. Fatty acid-induced angiogenesis in first trimester placental trophoblast cells: possible roles of cellular fatty acid-binding proteins. Life Sci. 2013;93(21):755–762.

    CAS  PubMed  Google Scholar 

  11. Stevens JF, Page JE. Xanthohumol and related prenylflavonoids from hops and beer: to your good health! Phytochemistry. 2004;65(10):1317–1330.

    CAS  PubMed  Google Scholar 

  12. Correia-Branco A, Azevedo CF, Araujo JR, et al. Xanthohumol impairs glucose uptake by a human first-trimester extravillous trophoblast cell line (HTR-8/SVneo cells) and impacts the process of placentation. Mol Hum Reprod. 2015;21(10):803–815.

    CAS  PubMed  Google Scholar 

  13. Araujo JR, Goncalves P, Martel F. Modulation of glucose uptake in a human choriocarcinoma cell line (BeWo) by dietary bioactive compounds and drugs of abuse. J Biochem. 2008;144(2):177–186.

    CAS  PubMed  Google Scholar 

  14. Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976;72:248–254.

    CAS  PubMed  Google Scholar 

  15. Bergmeyer HU, Bernt E. Lactate dehydrogenase. In: Bergmeyer HU, editor. Methods of Enzymatic Analysis, 2nd ed., New York: Academic Press, 1974;II:574–9.

    Google Scholar 

  16. Negrao R, Costa R, Duarte D, Gomes TT, Azevedo I, Soares R. Different effects of catechin on angiogenesis and inflammation depending on VEGF levels. J Nutr Biochem. 2013;24(2):435–444.

    CAS  PubMed  Google Scholar 

  17. Reinhart-King CA. Endothelial cell adhesion and migration. Methods Enzymol. 2008;443:45–64.

    CAS  PubMed  Google Scholar 

  18. Schmittgen TD, Livak KJ. Analyzing real-time PCR data by the comparative C(T) method. Nat Protoc. 2008;3(6):1101–1108.

    CAS  PubMed  Google Scholar 

  19. Muzyka ARM, Novikov A, Moskalenko E, Vysotsky A, Volokh V. Graphpad Prism From Windows. Version 5.03. 2009.

    Google Scholar 

  20. Pohl J, Ring A, Ehehalt R, Herrmann T, Stremmel W. New concepts of cellular fatty acid uptake: role of fatty acid transport proteins and of caveolae. Proc Nutr Soc. 2004;63(2):259–262.

    CAS  PubMed  Google Scholar 

  21. Kale A, Naphade N, Sapkale S, et al. Reduced folic acid, vitamin B12 and docosahexaenoic acid and increased homocysteine and cortisol in never-medicated schizophrenia patients: implications for altered one-carbon metabolism. Psychiatry Res. 2010;175(1–2):47–53.

    CAS  PubMed  Google Scholar 

  22. Qiu A, Jansen M, Sakaris A, et al. Identification of an intestinal folate transporter and the molecular basis for hereditary folate malabsorption. Cell. 2006;127(5):917–928.

    CAS  PubMed  Google Scholar 

  23. Schaiff WT, Bildirici I, Cheong M, Chern PL, Nelson DM, Sadovsky Y. Peroxisome proliferator-activated receptor-gamma and retinoid x receptor signaling regulate fatty acid uptake by primary human placental trophoblasts. J Clin Endocrinol Metab. 2005;90(7):4267–4275.

    CAS  PubMed  Google Scholar 

  24. Fournier T, Pavan L, Tarrade A, et al. The role of PPAR-gamma/ RXR-alpha heterodimers in the regulation of human trophoblast invasion. Ann N YAcad Sci. 2002;973:26–30.

    CAS  Google Scholar 

  25. Rauwel B, Mariame B, Martin H, et al. Activation of peroxisome proliferator-activated receptor gamma by human cytomegalovirus for de novo replication impairs migration and invasiveness of cytotrophoblasts from early placentas. J Virol. 2010;84(6):2946–2954.

    CAS  PubMed  Google Scholar 

  26. Bilban M, Haslinger P, Prast J, et al. Identification of novel trophoblast invasion-related genes: heme oxygenase-1 controls motility via peroxisome proliferator-activated receptor gamma. Endocrinology. 2009;150(2):1000–1013.

    CAS  PubMed  Google Scholar 

  27. Fisher SJ. The placental problem: linking abnormal cytotropho-blast differentiation to the maternal symptoms of preeclampsia. Reprod Biol Endocrinol. 2004;2:53.

    PubMed  PubMed Central  Google Scholar 

  28. Graham CH, Hawley TS, Hawley RG, et al. Establishment and characterization of first trimester human trophoblast cells with extended lifespan. Exp Cell Res. 1993;206(2):204–211.

    CAS  PubMed  Google Scholar 

  29. Johnsen GM, Weedon-Fekjaer MS, Tobin KA, Staff AC, Duttaroy AK. Long-chain polyunsaturated fatty acids stimulate cellular fatty acid uptake in human placental choriocarcinoma (BeWo) cells. Placenta. 2009;30(12):1037–1044.

    CAS  PubMed  Google Scholar 

  30. Bonen A, Chabowski A, Luiken JJ, Glatz JF. Is membrane transport of FFA mediated by lipid, protein, or both? Mechanisms and regulation of protein-mediated cellular fatty acid uptake: molecular, biochemical, and physiological evidence. Physiology (Bethesda). 2007;22:15–29.

    CAS  PubMed  Google Scholar 

  31. Doege H, Stahl A. Protein-mediated fatty acid uptake: novel insights from in vivo models. Physiology (Bethesda). 2006;21:259–268.

    CAS  PubMed  Google Scholar 

  32. Campbell FM, Gordon MJ, Dutta-Roy AK. Preferential uptake of long chain polyunsaturated fatty acids by isolated human placental membranes. Mol Cell Biochem. 1996;155(1):77–83.

    CAS  PubMed  Google Scholar 

  33. Qiu Q, Yang M, Tsang BK, Gruslin A. Both mitogen-activated protein kinase and phosphatidylinositol 3-kinase signalling are required in epidermal growth factor-induced human trophoblast migration. Mol Hum Reprod. 2004;10(9):677–684.

    CAS  PubMed  Google Scholar 

  34. Gangloff YG, Mueller M, Dann SG, et al. Disruption of the mouse mTOR gene leads to early postimplantation lethality and prohibits embryonic stem cell development. Mol Cell Biol. 2004;24(21):9508–9516.

    CAS  PubMed  PubMed Central  Google Scholar 

  35. Murakami M, Ichisaka T, Maeda M, et al. mTOR is essential for growth and proliferation in early mouse embryos and embryonic stem cells. Mol Cell Biol. 2004;24(15):6710–6718.

    CAS  PubMed  PubMed Central  Google Scholar 

  36. Wen HY, Abbasi S, Kellems RE, Xia Y. mTOR: a placental growth signaling sensor. Placenta. 2005;26(suppl A):S63–S69.

    PubMed  Google Scholar 

  37. Liu L, Wang Y, Shen C, et al. Benzo(a)pyrene inhibits migration and invasion of extravillous trophoblast HTR-8/SVneo cells via activation of the ERK and JNK pathway. J Appl Toxicol. 2016;36(7):946–955.

    PubMed  Google Scholar 

  38. Dimasuay KG, Boeuf P, Powell TL, Jansson T. Placental responses to changes in the maternal environment determine fetal growth. Front Physiol. 2016;7:12.

    PubMed  PubMed Central  Google Scholar 

  39. Jansson T, Aye IL,, Goberdhan DC. The emerging role of mTORC1 signaling in placental nutrient-sensing. Placenta. 2012;33(suppl 2):e23–e29.

    CAS  PubMed  PubMed Central  Google Scholar 

  40. Araujo JR, Correia-Branco A, Ramalho C, Keating E, Martel F. Gestational diabetes mellitus decreases placental uptake of longchain polyunsaturated fatty acids: involvement of long-chain acyl-CoA synthetase. J Nutr Biochem. 2013;24(10):1741–1750.

    CAS  PubMed  Google Scholar 

  41. Manach C, Williamson G, Morand C, Scalbert A, Rémésy C. Bioavailability and bioefficacy of polyphenols in humans. I. Review of 97 bioavailability studies. Am J Clin Nutr. 2005; 81(suppl 1):230S–242S.

    CAS  PubMed  Google Scholar 

  42. Forman BM, Chen J, Evans RM. Hypolipidemic drugs, polyun-saturated fatty acids, and eicosanoids are ligands for peroxisome proliferator-activated receptors alpha and delta. Proc Natl Acad Sci U S A. 1997;94(9):4312–4317.

    CAS  PubMed  PubMed Central  Google Scholar 

  43. Sampath H, Ntambi JM. Polyunsaturated fatty acid regulation of gene expression. Nutr Rev. 2004;62(9):333–339.

    PubMed  Google Scholar 

  44. Xu Y, Wang Q, Cook TJ, Knipp GT. Effect of placental fatty acid metabolism and regulation by peroxisome proliferator activated receptor on pregnancy and fetal outcomes. J Pharm Sci. 2007;96(10):2582–2606.

    CAS  PubMed  Google Scholar 

  45. Desvergne B, Michalik L, Wahli W. Transcriptional regulation of metabolism. Physiol Rev. 2006;86(2):465–514.

    CAS  PubMed  Google Scholar 

  46. Capobianco E, Jawerbaum A, Romanini MC, et al. 15-Deoxy-Delta12,14-prostaglandin J2 and peroxisome proliferator-activated receptor gamma (PPARgamma) levels in term placental tissues from control and diabetic rats: modulatory effects of a PPARgamma agonist on nitridergic and lipid placental metabolism. Reprod Fertil Dev. 2005;17(4):423–433.

    CAS  PubMed  Google Scholar 

  47. Schaiff WT, Knapp FF Jr, Barak Y, Biron-Shental T, Nelson DM, Sadovsky Y. Ligand-activated peroxisome proliferator activated receptor gamma alters placental morphology and placental fatty acid uptake in mice. Endocrinology. 2007;148(8):3625–3634.

    CAS  PubMed  Google Scholar 

  48. Barak Y, Nelson MC, Ong ES, et al. PPAR gamma is required for placental, cardiac, and adipose tissue development. Mol Cell. 1999;4(4):585–595.

    CAS  PubMed  Google Scholar 

  49. Tarrade A, Schoonjans K, Pavan L, et al. PPARgamma/RXRalpha heterodimers control human trophoblast invasion. J Clin Endocrinol Metab. 2001;86(10):5017–5024.

    CAS  PubMed  Google Scholar 

  50. McCarthy FP, Drewlo S, Kingdom J, Johns EJ, Walsh SK, Kenny LC. Peroxisome proliferator-activated receptor-gamma as a potential therapeutic target in the treatment of preeclampsia. Hypertension. 2011;58(2):280–286.

    CAS  PubMed  Google Scholar 

  51. Montellano PR. The mechanism of heme oxygenase. Curr Opin Chem Biol. 2000;4(2):221–227.

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Unit of Biochemistry, Department of Biomedicine, Faculty of Medicine, University of Porto, Porto, Portugal

    Ana Correia-Branco MSc, Elisa Keating PhD & Fátima Martel PhD

  2. I3S, Instituto de Investigação e Inovação em Saúude, University of Porto, Porto, Portugal

    Ana Correia-Branco MSc & Fátima Martel PhD

  3. CINTESIS, Center for Research in Health Technologies and Information Systems, University of Porto, Porto, Portugal

    Elisa Keating PhD

Authors
  1. Ana Correia-Branco MSc
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Elisa Keating PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Fátima Martel PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Fátima Martel PhD.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Correia-Branco, A., Keating, E. & Martel, F. Arachidonic Acid Reverses Xanthohumol-Induced Insufficiency in a Human First-Trimester Extravillous Trophoblast Cell Line (HTR-8/SVneo Cells). Reprod. Sci. 25, 1394–1405 (2018). https://doi.org/10.1177/1933719117746762

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1177/1933719117746762

Keywords

Search

Navigation