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The Effect of Repeated Umbilical Cord Occlusions on Pulmonary Surfactant Protein mRNA Levels in the Ovine Fetus

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Abstract

Objectives

In this study we sought to determine the effect of brief repeated umbilical cord occlusions (rUCO) on surfactant protein (SP) mRNA levels in the fetal sheep lung at two different gestational ages.

Methods

Fourteen fetuses at 112 to 115 days’ gestation (control n = 7, rUCO n = 7) and 15 fetuses at 130 to 133 days’ gestation (control n = 7, rUCO n = 8) were studied over 4 successive days with rUCO of 90 seconds duration pe formed every 30 minutes for 3 to 5 hours each day in the rUCO animals. Blood samples were collected for corticotrophin (ACTH) and Cortisol measurements. Animals were killed within 1 hour of the final cord occlusion. SP-A, -B, -C, and -D mRNA levels were determined in lung tissue using a ribonuclease protection assay.

Results

Cord occlusions resulted in temporary increases in circulating ACTH on day 1 with both gestational ages, but the elevations were blunted by day 4. Plasma Cortisol levels increased transiently with the larger effect being observed on day 4, in particular with the near-term group. With advancing gestational age there was a significant (P <.05) increase in the level of SP-A (control 112—115 days: 0.01 ± 0.01 vs control 130–133 days: 0.07 ± 0.02 fmol/mgRNA), SP-B (control 112–115 days: 0.02 ± 0.01 vs control 130–133 days: 0.07 ± 0.01 fmol/mg RNA) and SP-C (control 112–115 days: 0.13 ± 0.09 vs control 130–133 days: 0.51 ± 0.10 fmol/mg RNA), but not SP-D mRNA levels (control 112–115 days: 0.002 ± 0.002 vs control 130–133 days: 0.01 ± 0.002 fmol/mg RNA). At 112 to 115 days, there was no significant change in any of the SP mRNA levels following rUCO compared to controls. However, the same regime of rUCO at 130 to 133 days resulted in an 85% reduction in SP-A and SP-B mRNA content and a 66% reduction in SP-C mRNA levels compared to controls.

Conclusion

The surprising decrease in SP-A and SP-B mRNA levels, which contrasts with other studies, suggests intermittent asphyxial episodes impact differently on surfactant apoprotein mRNA expression than does prolonged hypoxia.

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References

  1. Dawes GS, Lobb MO, Mandruzzato G, Moulden M, Redman CW, Wheeler T. Large fetal heart rate decelerations at term associated with changes in fetal heart rate variation. Am J Obstet Gynecol 1993;168:105–111.

    Article  CAS  PubMed  Google Scholar 

  2. Westgate JA, Bennet L, Gunn AJ. Fetal heart rate variability changes during brief repeated umbilical corc occlusion in near term fetal sheep. Br J Obstet Gynaecol 1999;106:664–671.

    Article  CAS  PubMed  Google Scholar 

  3. Giussani DA, Unno N, Jenkins SL, et al. Dynamics of cardiovascular responses to repeated partial umbilical corc compression in late-gestation sheep fetus. Am J Physiol 1997;273:H2351–H2360.

    CAS  PubMed  Google Scholar 

  4. Green LR, Homan J, White SE, Richardson BS. Cardiovascular and metabolic responses to intermittent umbilical cord occlusion in the preterm ovine fetus. J Soc Gynecol Investig 1999;6:56–63.

    Article  CAS  PubMed  Google Scholar 

  5. Green LR, Kawagoe Y, Homan J, White SE, Richardson BS. Adaptation of cardiovascular responses to repetitive umbilical corc occlusion in the late gestation ovine fetus. J Physiol 2001;535:879–888.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Clapp JF, Peress NS, Wesley M, Mann LI. Brain damage after intermittent partial cord occlusion in the chronically instrumented fetal lamb. Am J Obstet Gynecol 1988;159:504–509.

    Article  CAS  PubMed  Google Scholar 

  7. Falkowski A, Hammond R, Han V, Richardson B. Apoptosis in the preterm and near term ovine fetal brain and the effect of intermittent umbilical cord occlusion. Dev Brain Res 2002;136:165–173.

    Article  CAS  Google Scholar 

  8. Rocha E, Hammond R, Richardson B. Necrotic cell injury in the preterm and near-term ovine fetal brain after intermittent umbilical cord occlusion. Am J Obstet Gynecol 2004;191:488–496.

    Article  PubMed  Google Scholar 

  9. Mescher EJ, Platzker AC, Ballard PL, Kitterman JA, Clements JA, Tooley WH. Ontogeny of tracheal fluid, pulmonary surfactant, and plasma corticoids in the fetal lamb. J Appl Physiol 1975;39:1017–1021.

    Article  CAS  PubMed  Google Scholar 

  10. Platzker AC, Kitterman JA, Mescher EJ, Clements JA, Tooley WH. Surfactant in the lung and tracheal fluid of the fetal lamb and acceleration of its appearance by dexamethasone. Pediatrics 1975;56:554–561.

    CAS  PubMed  Google Scholar 

  11. Randell SH, Silbajoris R, Young SL. Ontogeny of rat lung type II cells correlated with surfactant lipid and surfactant apoprotein expression. Am J Physiol 1991;260:L562–L570.

    Article  CAS  PubMed  Google Scholar 

  12. Schellhase DE, Emrie PA, Fisher JH, Shannon JM. Ontogeny of surfactant apoproteins in the rat. Pediatr Res 1989;26:167–174.

    Article  CAS  PubMed  Google Scholar 

  13. Cockshutt AM and Possmayer F. Metabolism of surfactant lipids and proteins in the developing lung. In: Robertson B, Van Golde LMG, Batenburg JJ, eds. Pulmonary surfactant: from molecular biology to clinical practice. Amsterdam, the Netherlands: Elsevier, 1992:339–377.

    Google Scholar 

  14. Moya FR, Gross I. Prevention of respiratory distress syndrome. Semin Perinatol 1988;12:348–358.

    CAS  PubMed  Google Scholar 

  15. Jobe AH and Ikegami M. Lung development and function in preterm infants in the surfactant treatment era. Annu Rev Physiol 2000;62:825–846.

    Article  CAS  PubMed  Google Scholar 

  16. deMello DE. Pulmonary pathology. Semin Neonatol 2004;9:311–329.

    Article  PubMed  Google Scholar 

  17. Hawgood S, Derrick M, and Poulain F. Structure and properties of surfactant protein B. Biochim Biophys Acta 1998;1408:150–160.

    Article  CAS  PubMed  Google Scholar 

  18. Johansson J. Structure and properties of surfactant protein C. Biochim Biophys Acta 1998;1408:161–172.

    Article  CAS  PubMed  Google Scholar 

  19. Whitsett JA, Weaver TE. Hydrophobic surfactant proteins in lung function and disease. N Engl J Med 2002;347:2141–2148.

    Article  PubMed  Google Scholar 

  20. Nogee LM. Alterations in SP-B and SP-C expression in neonatal lung disease. Annu Rev Physiol 2004;66:601–623.

    Article  CAS  PubMed  Google Scholar 

  21. McCormack FX and Whitsett JA. The pulmonary collectins, SP-A and SP-D, orchestrate innate immunity in the lung. J Clin Invest 2002;109:707–712.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Braems GA, Yao LJ, Inchley K, et al. Ovine surfactant protein cDNAs: use in studies on fetal lung growth and maturation after prolonged hypoxemia. Am J Physiol Lung Cell Mol Physiol 2000;278:L754–L764.

    Article  CAS  PubMed  Google Scholar 

  23. Braems G. Fetal hypoxemia on a molecular level: adaptive changes in the hypothalamic-pituitary-adrenal (HPA) axis and the lungs. Eur J Obstet Gynecol Reprod Biol 2003;110 Suppl 1:S63–S69.

    Article  CAS  PubMed  Google Scholar 

  24. Gagnon R, Langridge J, Inchley K, Murotsuki J, Possmayer F. Changes in surfactant-associated protein mRNA profile in growth-restricted fetal sheep. Am J Physiol 1999;276:L459–L465.

    Article  CAS  PubMed  Google Scholar 

  25. Cock ML, Albuquerque CA, Joyce BJ, Hooper SB, Harding R. Effects of intrauterine growth restriction on lung liquid dynamics and lung development in fetal sheep. Am J Obstet Gynecol 2001;184:209–216.

    Article  CAS  PubMed  Google Scholar 

  26. Green LR, Kawagoe Y, Fraser M, Challis JR, Richardson BS. Activation of the hypothalamic-pituitary-adrenal axis with repetitive umbilical cord occlusion in the preterm ovine fetus. J Soc Gynecol Investig 2000;7:224–232.

    Article  CAS  PubMed  Google Scholar 

  27. Kawagoe Y, Green LR, Fraser M, Challis JRG, Richardson BS. ACTH and cortisol responses to repetitive umbilical corc occlusion are altered during the latter part of gestation in the ovine fetus. J Soc Gypnecol Invest 1999;6 Suppl:115A–115A.

    Google Scholar 

  28. Matthews SG, Yang K, and Challis JR. Changes in glucocorticoid receptor mRNA in the developing ovine pituitary and the effects of exogenous cortisol. J Endocrinol 1995;144:483–490.

    Article  CAS  PubMed  Google Scholar 

  29. Unno N, Giussani DA, Hing WK, Ding XY, Collins JH, Nathanielsz after repeated partial umbilical cord occlusions in the late gestation ovine fetus. Endocrinology 1997;138:259–263.

    Article  CAS  PubMed  Google Scholar 

  30. Schellhase DE, Emrie PA, Fisher JH, Shannon JM. Ontogeny of surfactant apoproteins in the rat. Pediatr Res 1989;26:167–174.

    Article  CAS  PubMed  Google Scholar 

  31. Xu J, Yao LJ, Possmayer F. Regulation of mRNA levels for pulmonary surfactant-associated proteins in developing rabbit lung. Biochim Biophys Acta 1995;1254:302–310.

    Article  PubMed  Google Scholar 

  32. Tan RC, Ikegami M, Jobe AH, Yao LY, Possmayer F, Ballard PL. Developmental and glucocorticoid regulation of surfactant protein mRNAs in preterm lambs. Am J Physiol 1999;277:L1142–L1148.

    Article  CAS  PubMed  Google Scholar 

  33. Flecknoe SJ, Wallace MJ, Harding R, Hooper SBJ. Determination of alveolar epithelial cell phenotypes in fetal sheep: evidence for the involvement of basal lung expansion. J Physiol 2002;542:245–253.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Bachurski CJ, Ross GF, Ikegami M, Kramer Bw, Jobe AH. Intra-amniotic endotoxin increases pulmonary surfactant proteins and induces SP-B processing in fetal sheep. Am J Physiol Lung Cell Mol Physiol 2001;280:L279–L285.

    Article  CAS  PubMed  Google Scholar 

  35. Miakotina OL, Synder JM. TNF-alpha inhibits SP-A gene expression in lung epithelial cells via p38 MAPK. Am J Physiol Lung Cell Mol Physiol 2002;283:L418–L427.

    Article  CAS  PubMed  Google Scholar 

  36. Hallman M, Glumoff V, Ramet M. Surfactant in respiratory distress syndrome and lung injury. Comp Biochem Physiol A Mol Integr Physiol 2001;129:287–294.

    Article  CAS  PubMed  Google Scholar 

  37. Pryhuber GS, Khalak R, Zhao Q. Regulation of surfactant proteins A and B by TNF-alpha and phorbol ester independent of NF-kappa B. Am J Physiol 1998;274:L289–L295.

    Article  CAS  PubMed  Google Scholar 

  38. Hill DJ, Strain AJ, Milner RD. Presence of transforming growth factor-beta-like activity in multiple fetal rat tissues. Cell Biol Int Rep 1986;10:915–922.

    Article  CAS  PubMed  Google Scholar 

  39. Beers MF, Solarin KO, Guttentag SH, et al. TGF-beta1 inhibits surfactant component expression and epithelial cell maturation in cultured human fetal lung. Am J Physiol 1998;275:L950–L960.

    CAS  PubMed  Google Scholar 

  40. Liggins GC, Kitterman JA, Campos GA, et al. Pulmonary maturation in the hypophysectomised ovine fetus. Differential responses to adrenocorticotrophin and cortisol. J Dev Physiol 1981;3:1–14.

    CAS  PubMed  Google Scholar 

  41. Ballard PL, Hawgood S, Liley H, et al. Regulation of pulmonary surfactant apoprotein SP 28–36 gene in fetal human lung. Proc Natl Acad Sci U S A 1986;83:9527–9531.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Polk DH, Ikegami M, Jobe AH, et al. Postnatal lung function in preterm lambs: Effects of a single exposure to betamethasone and thyroid hormones. Am J Obstet Gynecol 1995;172:872–881.

    Article  CAS  PubMed  Google Scholar 

  43. Polk DH, Ikegami M, Jobe AH, Sly P, Kohan R, Newnham J. Preterm lung function after retreatment with antenatal betamethasone in preterm lambs. Am J Obstet Gynecol 1997;176:308–315.

    Article  CAS  PubMed  Google Scholar 

  44. Jauniaux E, Ramsay B, Peellaerts C, Scholler Y. Perinatal features of pregnancies complicated by nuchal cord. Am J Perinatol 1995;12:255–258.

    Article  CAS  PubMed  Google Scholar 

  45. Rhoades DA, Latza U, Mueller BA. Risk factors and outcomes associated with nuchal cord. A population-based study. J Reprod Med 1999;44:39–45.

    CAS  PubMed  Google Scholar 

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Correspondence to Alan D. Bocking MD.

Additional information

Supported by the Canadian Institutes of Health Research and the Dr D. Whaley Post-Doctoral Fellowship.

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Nardo, L., Zhao, L., Green, L. et al. The Effect of Repeated Umbilical Cord Occlusions on Pulmonary Surfactant Protein mRNA Levels in the Ovine Fetus. Reprod. Sci. 12, 510–517 (2005). https://doi.org/10.1016/j.jsgi.2005.07.004

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  • DOI: https://doi.org/10.1016/j.jsgi.2005.07.004

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