Skip to main content

Advertisement

SpringerLink
Log in

Mechanical Stretch Increases Brain Natriuretic Peptide Production and Secretion in the Human Fetal Membranes

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

Abstract

Brain natriuretic peptide (BNP) is synthesized by human fetal membranes, both the amnion and chorion. This locally produced BNP inhibits the contraction of the human myometrium, contributing to the maintenance of myometrial quiescence during pregnancy. We tested the hypothesis that BNP production is increased by fetal membrane stretching, which is predicted to occur in the expanding uterus, and inhibited by epidermal growth factor (EGF), whose production in the fetal membranes increases in late pregnancy. Term fetal membranes were obtained during elective cesarean delivery before labor. Sections of membranes were placed in an isolated chamber containing DMEM: F12 medium (37°C) and stretched with a 35 g weight. Medium and tissue samples were collected at 0, 3, 6, 18, and 24 hours for measurement of messenger RNA (mRNA) and BNP levels in the presence/absence of EGF (2 × 10−9 mol/L). Inducible nitric oxide synthase (iNOS) and β-actin were also evaluated to discard a nonspecific effect of mechanical stretch on protein expression. We found that amnion and chorion stretching increased the BNP mRNA (reverse transcription–polymerase chain reaction [RT-PCR]) and protein (radioimmunosorbent assay [RIA]) levels from 18 hours onward. The effect of stretching was inhibited by EGF (2 × 10−9 mol/L). Stretch did not increase iNOS or β-actin protein levels. We concluded that chorion and amnion stretching may increase BNP expression in the fetal membranes during pregnancy, while increasing biological activity of EGF may decrease BNP production in the chorion and amnion late in pregnancy. We postulate BNP is an important regulator of myometrial contractility during pregnancy, and its production is modulated by both stretch and progressive increase in EGF levels during pregnancy.

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. Carvajal JA, Weiner CP. Mechanisms underlying myometrial quiescence during pregnancy. Fetal Matern Med Rev. 2003;14(3):209–237.

    Article  Google Scholar 

  2. Carvajal JA. Determinismo del Parto. In: Pérez Sánchez A, Donoso E, eds. Obstetricia. Cuarta Editićn ed. Santiago, Chile: Editorial Mediterráneo Ltda.; 2011:322–339.

    Google Scholar 

  3. Carvajal JA, Buhimschi IA, Thompson LP, Aguan K, Weiner CP. Chorion releases a factor that inhibits oxytocin-stimulated myometrial contractility in the pregnant guinea pig. Hum Reprod. 2001;16(4):638–643.

    Article  CAS  Google Scholar 

  4. Carvajal JA, Thompson LP, Weiner CP. Chorion-induced myometrial relaxation is mediated by large-conductance Ca2+-activated K+ channel opening in the guinea pig. Am J Obstet Gynecol. 2003;188(1):84–91.

    Article  CAS  Google Scholar 

  5. Carvajal JA, Vidal RJ, Cuello MA, Poblete JA, Weiner CP. Mechanisms of paracrine regulation by fetal membranes of human uterine quiescence. J Soc Gynecol Investig. 2006;13(5):343–349.

    Article  CAS  Google Scholar 

  6. Itoh H, Sagawa N, Hasegawa M, et al. Brain natriuretic peptide is present in the human amniotic fluid and is secreted from amnion cells. J Clin Endocrinol Metab. 1993;76(4):907–911.

    CAS  PubMed  Google Scholar 

  7. Itoh H, Sagawa N, Hasegawa M, et al. Expression of biologically active receptors for natriuretic peptides in the human uterus during pregnancy. Biochem Biophys Res Commun. 1994;203(1):602–607.

    Article  CAS  Google Scholar 

  8. Carvajal JA, Aguan K, Thompson LP, Buhimschi IA, Weiner CP. Natriuretic peptide-induced relaxation of myometrium from the pregnant guinea pig is not mediated by guanylate cyclase activation. J Pharmacol Exp Ther. 2001;297(1):181–188.

    CAS  PubMed  Google Scholar 

  9. Carvajal JA, Delpiano AM, Cuello MA, et al. Brain natriuretic peptide (BNP) produced by the human chorioamnion may mediate pregnancy myometrial quiescence. Reprod Sci. 2009;16(1):32–42.

    Article  CAS  Google Scholar 

  10. Langenickel T, Pagel I, Hohnel K, Dietz R, Willenbrock R. Differential regulation of cardiac ANP and BNP mRNA in different stages of experimental heart failure. Am J Physiol Heart Circ Physiol. 2000;278(5):H1500–H1506.

    Article  CAS  Google Scholar 

  11. Magga J, Vuolteenaho O, Marttila M, Ruskoaho H. Endothelin-1 is involved in stretch-induced early activation of B-type natriuretic peptide gene expression in atrial but not in ventricular myocytes: acute effects of mixed ET(A)/ET(B) and AT1 receptor antagonists in vivo and in vitro. Circulation. 1997;96(9):3053–3062.

    Article  CAS  Google Scholar 

  12. Mantymaa P, Vuolteenaho O, Marttila M, Ruskoaho H. Atrial stretch induces rapid increase in brain natriuretic peptide but not in atrial natriuretic peptide gene expression in vitro. Endocrinology. 1993;133(3):1470–1473.

    Article  CAS  Google Scholar 

  13. Liang F, Wu J, Garami M, Gardner DG. Mechanical strain increases expression of the brain natriuretic peptide gene in rat cardiac myocytes. J Biol Chem. 1997;272(44):28050–28056.

    Article  CAS  Google Scholar 

  14. Itoh H, Sagawa N, Hasegawa M, et al. Transforming growth factor-beta stimulates, and glucocorticoids and epidermal growth factor inhibit brain natriuretic peptide secretion from cultured human amnion cells. J Clin Endocrinol Metab. 1994;79(1):176–182.

    CAS  PubMed  Google Scholar 

  15. Chomczynski P, Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987;162(1):156–159.

    Article  CAS  Google Scholar 

  16. LaPointe MC. Molecular regulation of the brain natriuretic peptide gene. Peptides. 2005;26(6):944–956.

    Article  CAS  Google Scholar 

  17. Riemer RK, Roberts JM. Activation of uterine smooth muscle contraction: implications for eicosanoid action and interactions. Semin Perinatol. 1986;10(4):276–287.

    CAS  PubMed  Google Scholar 

  18. Liang F, Gardner DG. Autocrine/paracrine determinants of strain-activated brain natriuretic peptide gene expression in cultured cardiac myocytes. J Biol Chem. 1998;273(23):14612–14619.

    Article  CAS  Google Scholar 

  19. Liang F, Atakilit A, Gardner DG. Integrin dependence of brain natriuretic peptide gene promoter activation by mechanical strain. J Biol Chem. 2000;275(27):20355–20360.

    Article  CAS  Google Scholar 

  20. Liang F, Lu S, Gardner DG. Endothelin-dependent and -independent components of strain-activated brain natriuretic peptide gene transcription require extracellular signal regulated kinase and p38 mitogen-activated protein kinase. Hypertension. 2000;35(1 pt 2):188–192.

    Article  CAS  Google Scholar 

  21. Shyu KG. Cellular and molecular effects of mechanical stretch on vascular cells and cardiac myocytes. Clin Sci (Lond). 2009;116(5):377–389.

    Article  CAS  Google Scholar 

  22. Liang F, Gardner DG. Mechanical strain activates BNP gene transcription through a p38/NF-kappaB-dependent mechanism. J Clin Invest. 1999;104(11):1603–1612.

    Article  CAS  Google Scholar 

  23. Gargiulo AR, Khan-Dawood FS, Dawood MY. Epidermal growth factor receptors in uteroplacental tissues in term pregnancy before and after the onset of labor. J Clin Endocrinol Metab. 1997;82(1):113–117.

    Article  CAS  Google Scholar 

  24. Pasetto N, Petrozza V, Ticconi C, et al. Influence of labour on epidermal growth factor receptor distribution of the human chorion at term gestation. Gynecol Obstet Invest. 1993;35(2):99–102.

    Article  CAS  Google Scholar 

  25. Romero R, Wu YK, Oyarzun E, Hobbins JC, Mitchell MD. A potential role for epidermal growth factor/alpha-transforming growth factor in human parturition. Eur J Obstet Gynecol Reprod Biol. 1989;33(1):55–60.

    Article  CAS  Google Scholar 

  26. Varner MW, Dildy GA, Hunter C, Dudley DJ, Clark SL, Mitchell MD. Amniotic fluid epidermal growth factor levels in normal and abnormal pregnancies. J Soc Gynecol Investig. 1996;3(1):17–19.

    Article  CAS  Google Scholar 

  27. Ackerman WEt, Rovin BH, Kniss DA. Epidermal growth factor and interleukin-1beta utilize divergent signaling pathways to synergistically upregulate cyclooxygenase-2 gene expression in human amnion-derived WISH cells. Biol Reprod. 2004;71(6):2079–2086.

    Article  CAS  Google Scholar 

  28. Xia G, Martin AE, Besner GE. Heparin-binding EGF-like growth factor downregulates expression of adhesion molecules and infiltration of inflammatory cells after intestinal ischemia/reperfusion injury. J Pediatr Surg. 2003;38(3):434–439.

    Article  Google Scholar 

  29. Ning Y, Zeineldin R, Liu Y, Rosenberg M, Stack MS, Hudson LG. Down-regulation of integrin alpha2 surface expression by mutant epidermal growth factor receptor (EGFRvIII) induces aberrant cell spreading and focal adhesion formation. Cancer Res. 2005;65(20):9280–9286.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Unidad de Medicina Materno Fetal, Centro de Investigaciones Médicas, División de Obstetricia y Ginecología, Pontificia Universidad Católica de Chile, Marcoleta 391, Santiago, Chile

    Jorge A. Carvajal MD, PhD, Ana M. Delpiano MSc, Mauricio A. Cuello MD & José A. Poblete MD

Authors
  1. Jorge A. Carvajal MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ana M. Delpiano MSc
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mauricio A. Cuello MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. José A. Poblete MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jorge A. Carvajal MD, PhD.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Carvajal, J.A., Delpiano, A.M., Cuello, M.A. et al. Mechanical Stretch Increases Brain Natriuretic Peptide Production and Secretion in the Human Fetal Membranes. Reprod. Sci. 20, 597–604 (2013). https://doi.org/10.1177/1933719112459219

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1177/1933719112459219

Keywords

Search

Navigation