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Brain Natriuretic Peptide (BNP) Produced by the Human Chorioamnion May Mediate Pregnancy Myometrial Quiescence

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Abstract

We aim to demonstrate that Brain Natriuretic Peptide (BNP) is synthesized and released from the fetal membranes and mediates pregnancy myometrial quiescence. Myometrium and fetal membranes (FM) were obtained from term and preterm pregnancies at the time of cesarean section, either in labor or not in labor. BNP was measured in term and preterm FM, in culture cells, and conditioned media. We found BNP (but not ANP or CNP) inhibited contractions of preterm, but not term, human myometrium. BNP (both protein and mRNA) was detected in all tissues, conditioned media and cultured cells. BNP was higher in samples from preterm women not in labor compared to those at term not in labor. BNP concentrations were significantly reduced in women in spontaneous preterm labor. We conclude that locally produced BNP may be involved in generating myometrial quiescence during pregnancy. Further, a premature decrease of BNP production may cause preterm labor.

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References

  1. Carvajal JA, Weiner CP. Mechanisms Underlying Myometrial Quiescence During Pregnancy. Fetal Matern Med Rev. 2003;14:209–237.

    Article  Google Scholar 

  2. Smith R. Parturition. N Engl J Med. 2007;356:271–283.

    Article  CAS  PubMed  Google Scholar 

  3. Lopez Bernal A. The regulation of uterine relaxation. Semin Cell Dev Biol. 2007;18:340–347.

    Article  CAS  PubMed  Google Scholar 

  4. 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;16:638–643.

    Article  CAS  PubMed  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 Invest. 2006;13: 343–349.

    Article  CAS  Google Scholar 

  6. 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;188:84–91.

    Article  CAS  PubMed  Google Scholar 

  7. Collins PL, Idriss E, Moore JJ. Human fetal membranes inhibit spontaneous uterine contractions. J Clin Endocrinol Metab. 1993;77:1479–1484.

    CAS  PubMed  Google Scholar 

  8. Collins PL, Idriss E, Moore JJ. Fetal membranes inhibit prostaglandin but not oxytocin-induced uterine contractions. Am J Obstet Gynecol. 1995;172(4 pt 1):1216–1223.

  9. Collins PL, Moore JJ, Idriss E, Kulp TM. Human fetal membranes inhibit calcium L-channel activated uterine contractions. Am J Obstet Gynecol. 1996;175:1173–1179.

    Article  CAS  PubMed  Google Scholar 

  10. Emery SP, Idriss E, Richmonds C, Collins PL. Human fetal membranes release a Ca++ channel inhibitor. Am J Obstet Gynecol. 1998;179:989–993.

    CAS  Google Scholar 

  11. Carroll EM, Gianopoulos JG, Collins PL. Abnormality of calcium channel inhibitor released from fetal membranes in preterm labor. Am J Obstet Gynecol. 2001;184:356–362.

    Article  CAS  PubMed  Google Scholar 

  12. Buxton IL. Regulation of uterine function: a biochemical conundrum in the regulation of smooth muscle relaxation. Mol Pharmacol. 2004;65:1051–1059.

    Article  CAS  PubMed  Google Scholar 

  13. Price SA, Bernal AL. Uterine quiescence: the role of cyclic AMP. Exp Physiol. 2001;86:265–272.

    Article  CAS  PubMed  Google Scholar 

  14. Yuan W, Lopez Bernal A. Cyclic AMP signaling pathways in the regulation of uterine relaxation. BMC Pregnancy Childbirth. 2007;7(suppl 1):S10.

  15. Europe-Finner GN, Phaneuf S, Tolkovsky AM, Watson SP, Lopez Bernal A. Down-regulation of G alpha s in human myometrium in term and preterm labor: a mechanism for parturition. J Clin Endocrinol Metab. 1994;79:1835–1839.

    CAS  PubMed  Google Scholar 

  16. Lindeman KS, Forrester DJ, Hirshman CA, Emala CW. Myometrial adenylyl cyclase protein decreases on the last day of pregnancy in the rat. Biol Reprod. 2000;62:1422–1426.

    Article  CAS  PubMed  Google Scholar 

  17. Sanborn BM, Yue C, Wang W, Dodge KL. G protein signaling pathways in myometrium: affecting the balance between contraction and relaxation. Rev Reprod. 1998;3:196–205.

    Article  CAS  PubMed  Google Scholar 

  18. Arkinstall SJ, Jones CT. Influence of pregnancy on G-protein coupling to adenylate cyclase activation in guinea-pig myometrium. J Endocrinol. 1990;127:15–21.

    Article  CAS  PubMed  Google Scholar 

  19. Europe-Finner GN, Phaneuf S, Watson SP, Lopez Bernal A. Identification and expression of G-proteins in human myometrium: up-regulation of G alpha s in pregnancy. Endocrinology. 1993;132:2484–2490.

    Article  CAS  PubMed  Google Scholar 

  20. Europe-Finner GN, Phaneuf S, Cartwright E, Mardon HJ, Lopez Bernal A. Expression of human myometrial G alpha s messenger ribonucleic acid transcript during pregnancy and labour: involvement of alternative splicing pathways. J Mol Endocrinol. 1997;18:15–25.

    Article  CAS  PubMed  Google Scholar 

  21. Gsell S, Eschenhagen T, Kaspareit G, et al. Apparent up-regulation of stimulatory G-protein alpha subunits in the pregnant human myometrium is mimicked by elevated smoothelin expression. Faseb J. 2000;14:17–26.

    Article  CAS  PubMed  Google Scholar 

  22. Price SA, Pochun I, Phaneuf S, Lopez Bernal A. Adenylyl cyclase isoforms in pregnant and non-pregnant human myometrium. J Endocrinol. 2000;164:21–30.

    Article  CAS  PubMed  Google Scholar 

  23. Mhaouty-Kodja S, Bouet-Alard R, Limon-Boulez I, Maltier JP, Legrand C. Molecular diversity of adenylyl cyclases in human and rat myometrium. Correlation with global adenylyl cyclase activity during mid- and term pregnancy. J Biol Chem. 1997;272:31100–31106.

    Article  CAS  PubMed  Google Scholar 

  24. Brodt-Eppley J, Myatt L. Prostaglandin receptors in lower segment myometrium during gestation and labor. Obstet Gynecol. 1999;93:89–93.

    CAS  PubMed  Google Scholar 

  25. Grigsby PL, Sooranna SR, Adu-Amankwa B, et al. Regional expression of prostaglandin E2 and F2alpha receptors in human myometrium, amnion, and choriodecidua with advancing gestation and labor. Biol Reprod. 2006;75:297–305.

    Article  CAS  PubMed  Google Scholar 

  26. Dong YL, Fang L, Kondapaka S, Gangula PR, Wimalawansa SJ, Yallampalli C. Involvement of calcitonin gene-related peptide in the modulation of human myometrial contractility during pregnancy. J Clin Invest. 1999;104:559–565.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Goharkhay N, Lu J, Felix JC, Wing DA. Expression of calcitonin gene-related peptide-receptor component protein (CGRP-RCP) in human myometrium in differing physiological states and following misoprostol administration. Am J Perinatol. 2007;24:497–500.

    Article  PubMed  Google Scholar 

  28. Yallampalli C, Gangula PR, Kondapaka S, Fang L, Wimalawansa S. Regulation of calcitonin gene-related peptide receptors in the rat uterus during pregnancy and labor and by progesterone. Biol Reprod. 1999;61:1023–1030.

    Article  CAS  PubMed  Google Scholar 

  29. Engstrom T, Bratholm P, Vilhardt H, Christensen NJ. Effect of pregnancy on rat myometrial beta 2-adrenoceptor mRNA and isoproterenol-induced relaxation of isolated uterine strips. J Endocrinol. 1997;153:393–399.

    Article  CAS  PubMed  Google Scholar 

  30. Gaspar R, Ducza E, Mihalyi A, et al. Pregnancy-induced decrease in the relaxant effect of terbutaline in the late-pregnant rat myometrium: role of G-protein activation and progesterone. Reproduction. 2005;130:113–122.

    Article  CAS  PubMed  Google Scholar 

  31. Litime MH, Pointis G, Breuiller M, Cabrol D, Ferre F. Disappearance of beta-adrenergic response of human myometrial adenylate cyclase at the end of pregnancy. J Clin Endocrinol Metab. 1989;69:1–6.

    Article  CAS  PubMed  Google Scholar 

  32. Zuo J, Lei ZM, Rao CV. Human myometrial chorionic gonadotropin/luteinizing hormone receptors in preterm and term deliveries. J Clin Endocrinol Metab. 1994;79:907–911.

    CAS  PubMed  Google Scholar 

  33. Grammatopoulos DK. The role of CRH receptors and their agonists in myometrial contractility and quiescence during pregnancy and labour. Front Biosci. 2007;12:561–571.

    Article  CAS  PubMed  Google Scholar 

  34. Grammatopoulos DK, Hillhouse EW. Role of corticotropin-releasing hormone in onset of labour. Lancet. 1999;354:1546–1549.

    Article  CAS  PubMed  Google Scholar 

  35. Challis JRG, Matthews SG, Gibb W, Lye SJ. Endocrine and paracrine regulation of birth at term and preterm. Endocr Rev. 2000;21:514–550.

    CAS  PubMed  Google Scholar 

  36. Weiner CP, Knowles RG, Nelson SE, Stegink LD. Pregnancy increases guanosine 3,’5’-monophosphate in the myometrium independent of nitric oxide synthesis. Endocrinology. 1994;135:2473–2478.

    Article  CAS  PubMed  Google Scholar 

  37. Buhimschi I, Yallampalli C, Dong YL, Garfield RE. Involvement of a nitric oxide-cyclic guanosine monophosphate pathway in control of human uterine contractility during pregnancy. Am J Obstet Gynecol. 1995;172:1577–1584.

    Article  CAS  PubMed  Google Scholar 

  38. Telfer JF, Itoh H, Thomson AJ, et al. Activity and expression of soluble and particulate guanylate cyclases in myometrium from nonpregnant and pregnant women: down-regulation of soluble guanylate cyclase at term. J Clin Endocrinol Metab. 2001;86:5934–5943.

    Article  CAS  PubMed  Google Scholar 

  39. Carvajal JA, Germain AM, Huidobro-Toro JP, Weiner CP. Molecular mechanism of cGMP-mediated smooth muscle relaxation. J Cell Physiol. 2000;184:409–420.

    Article  CAS  PubMed  Google Scholar 

  40. Yallampalli C, Izumi H, Byam-Smith M, Garfield RE. An L-arginine-nitric oxide-cyclic guanosine monophosphate system exists in the uterus and inhibits contractility during pregnancy. Am J Obstet Gynecol. 1994;170(1 pt 1):175–185.

  41. Zhou XB, Wang GX, Ruth P, Huneke B, Korth M. BK(Ca) channel activation by membrane-associated cGMP kinase may contribute to uterine quiescence in pregnancy. Am J Physiol Cell Physiol. 2000;279:C1751–1759.

    Article  CAS  PubMed  Google Scholar 

  42. Bradley KK, Buxton IL, Barber JE, McGaw T, Bradley ME. Nitric oxide relaxes human myometrium by a cGMP-independent mechanism. Am J Physiol. 1998;275(6 pt 1): C1668-C1673.

  43. Buxton IL, Kaiser RA, Malmquist NA, Tichenor S. NO-induced relaxation of labouring and non-labouring human myometrium is not mediated by cyclic GMP. Br J Pharmacol. 2001;134:206–214.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Cea LB. Natriuretic peptide family: new aspects. Curr Med Chem Cardiovasc Hematol Agents. 2005;3:87–98.

    Article  CAS  PubMed  Google Scholar 

  45. Graham CH, Watson JD, Blumenfeld AJ, Pang SC. Expression of atrial natriuretic peptide by third-trimester placental cytotrophoblasts in women. Biol Reprod. 1996;54:834–840.

    Article  CAS  PubMed  Google Scholar 

  46. 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;76:907–911.

    CAS  PubMed  Google Scholar 

  47. 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;203:602–607.

    Article  CAS  PubMed  Google Scholar 

  48. 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;297:181–188.

    CAS  PubMed  Google Scholar 

  49. Buhimschi CS, Buhimschi IA, Zhao G, et al. Biomechanical properties of the lower uterine segment above and below the reflection of the urinary bladder flap. Obstet Gynecol. 2007;109:691–700.

    Article  PubMed  Google Scholar 

  50. Suga S, Nakao K, Hosoda K, et al. Receptor selectivity of natriuretic peptide family, atrial natriuretic peptide, brain natriuretic peptide, and C-type natriuretic peptide. Endocrinology. 1992;130:229–239.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  52. Lundin-Schiller S, Mitchell MD. Prostaglandin production by human chorion laeve cells in response to inflammatory mediators. Placenta. 1991;12:353–363.

    Article  CAS  PubMed  Google Scholar 

  53. Okita JR, Sagawa N, Casey ML, Snyder JM. A comparison of human amnion tissue and amnion cells in primary culture by morphological and biochemical criteria. In Vitro. 1983;19: 117–126.

    Article  CAS  PubMed  Google Scholar 

  54. Hennan JK, Diamond J. Evidence that spontaneous contractile activity in the rat myometrium is not inhibited by NO-mediated increases in tissue levels of cyclic GMP. Br J Pharmacol. 1998;123:959–967.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Villar IC, Panayiotou CM, Sheraz A, et al. Definitive role for natriuretic peptide receptor-C in mediating the vasorelaxant activity of C-type natriuretic peptide and endothelium-derived hyperpolarising factor. Cardiovasc Res. 2007;74: 515–525.

    Article  CAS  PubMed  Google Scholar 

  56. Rose RA, Giles WR. Natriuretic peptide C receptor signalling in the heart and vasculature. J Physiol. 2008;586: 353–366.

    Article  CAS  PubMed  Google Scholar 

  57. Lev-Sagie A, Bar-Oz B, Salpeter L, Hochner-Celnikier D, Arad I, Nir A. Plasma concentrations of N-terminal Pro-B-Type natriuretic peptide in pregnant women near labor and during early puerperium. Clin Chem. 2005;51: 1909–1910.

    Article  CAS  PubMed  Google Scholar 

  58. Bar-Oz B, Lev-Sagie A, Arad I, Salpeter L, Nir A. N-terminal pro-B-type natriuretic peptide concentrations in mothers just before delivery, in cord blood, and in newborns. Clin Chem. 2005;51:926–927.

    Article  CAS  PubMed  Google Scholar 

  59. Itoh H, Sagawa N, Nanno H, Mori T, Mukoyama M, Nakao K. Impaired guanosine 3,’5’-cyclic phosphate production in severe pregnancy-induced hypertension with high plasma levels of atrial and brain natriuretic peptides. Endocr J. 1997;44:389–393.

    Article  CAS  PubMed  Google Scholar 

  60. Lauria MR, Standley CA, Sorokin Y, et al. Brain natriuretic peptide and cyclic guanosine-3, ′5′ monophosphate in preeclampsia. J Matern Fetal Med. 1996;5:128–131.

    CAS  PubMed  Google Scholar 

  61. Fleming SM, O’Byrne L, Grimes H, Daly KM, Morrison JJ. Amino-terminal pro-brain natriuretic peptide in normal and hypertensive pregnancy. Hypertens Pregnancy. 2001;20: 169–175.

    Article  CAS  PubMed  Google Scholar 

  62. Resnik JL, Hong C, Resnik R, et al. Evaluation of B-type natriuretic peptide (BNP) levels in normal and preeclamptic women. Am J Obstet Gynecol. 2005;193:450–454.

    Article  CAS  PubMed  Google Scholar 

  63. Kale A, Kale E, Yalinkaya A, Akdeniz N, Canoruc N. The comparison of amino-terminal probrain natriuretic peptide levels in preeclampsia and normotensive pregnancy. J Perinat Med. 2005;33:121–124.

    Article  CAS  PubMed  Google Scholar 

  64. Girsen A, Ala-Kopsala M, Makikallio K, Vuolteenaho O, Rasanen J. Cardiovascular hemodynamics and umbilical artery N-terminal peptide of proB-type natriuretic peptide in human fetuses with growth restriction. Ultrasound Obstet Gynecol. 2007;29:296–303.

    Article  CAS  PubMed  Google Scholar 

  65. 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;79:176–182.

    CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Departamento de Obstetricia y Ginecología, Unidad de Medicina Materno Fetal, Santiago, Chile

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

  2. Department of Obstetrics and Gynecology, Faculty of Medicine, Santiago, Chile

    Paola C. Casanello PhD & Luis A. Sobrevia PhD

  3. Centro de Investigaciones Mídicas, Pontificia Universidad Católica de Chile, Marcoleta 391, Santiago, Chile

    Carl P. Weiner MD

  4. Department of Obstetrics and Gynecology, University of Kansas School of Medicine, Kansas City, Kansas, USA

    Carl P. Weiner MD

Authors
  1. Jorge A. Carvajal MD, PhD
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  2. Ana M. Delpiano MS
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  3. Mauricio A. Cuello MD
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  4. José A. Poblete MD
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  5. Paola C. Casanello PhD
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  6. Luis A. Sobrevia PhD
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  7. Carl P. Weiner MD
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Correspondence to Jorge A. Carvajal MD, PhD.

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Carvajal, J.A., Delpiano, A.M., Cuello, M.A. et al. Brain Natriuretic Peptide (BNP) Produced by the Human Chorioamnion May Mediate Pregnancy Myometrial Quiescence. Reprod. Sci. 16, 32–42 (2009). https://doi.org/10.1177/1933719108324137

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