Skip to main content
Log in

Intrauterine Lipopolysaccharide-Induced Chorioamnionitis in a Sheep: Does It Affect the Auditory System?

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

Abstract

Background

Fetal exposure to in utero inflammation such as chorioamnionitis is related to central nervous system injury. We hypothesized that chorioamnionitis can provoke inflammatory changes in the perilymph and alter hearing outcome.

Methods

Pregnant ewes were randomized into 2 groups: intrauterine injection with lipopolysaccharide (LPS; n = 19) or saline (n = 21). In the first experiment, fetal perilymph samples were taken for cytokine analysis. In the second experiment, consecutive bone-conducted auditory brain stem responses were obtained from 1 to 7 months after birth.

Results

Perilymph samples showed a significant elevation in interleukin 8 in the LPS group. Auditory brain stem response analysis demonstrated higher response thresholds and a prolongation of absolute peak V and interpeak intervals I to V and III to V in the LPS group compared to sham treatment.

Conclusion

Our study confirms the hypothesis that an intrauterine inflammation by LPS can result in a fetal perilymphatic inflammatory response and functional impaired hearing outcomes after birth in a sheep model.

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

Access this article

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

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Gantert M, Been JV, Gavilanes AW, Garnier Y, Zimmermann LJ, Kramer BW. Chorioamnionitis: a multiorgan disease of the fetus? J Perinatol. 2010;30 suppl:S21–S30.

    PubMed  Google Scholar 

  2. Wu YW, Colford JM Jr. Chorioamnionitis as a risk factor for cerebral palsy: a meta-analysis. JAMA. 2000;284(11):1417–1424.

    CAS  PubMed  Google Scholar 

  3. Leviton A, Paneth N, Reuss ML, et al. Maternal infection, fetal inflammatory response, and brain damage in very low birth weight infants. Developmental Epidemiology Network Investigators. Pediatr Res. 1999;46(5):566–575.

    CAS  PubMed  Google Scholar 

  4. Shatrov JG, Birch SC, Lam LT, Quinlivan JA, McIntyre S, Mendz GL. Chorioamnionitis and cerebral palsy: a meta-analysis. Obstet Gynecol. Aug 2010;116(2 Pt 1):387–392.

    PubMed  Google Scholar 

  5. Wu YW, Escobar GJ, Grether JK, Croen LA, Greene JD, Newman TB. Chorioamnionitis and cerebral palsy in term and near-term infants. JAMA. 2003;290(20):2677–2684.

    CAS  PubMed  Google Scholar 

  6. Mikkola K, Ritari N, Tommiska V, et al. Neurodevelopmental outcome at 5 years of age of a national cohort of extremely low birth weight infants who were born in 1996–1997. Pediatrics. 2005;116(6):1391–1400.

    PubMed  Google Scholar 

  7. Mackay DF, Smith GC, Dobbie R, Cooper SA, Pell JP. Obstetric factors and different causes of special educational need: retrospective cohort study of 407,503 schoolchildren. BJOG. 2013; 120(3):297–307.

    CAS  PubMed  Google Scholar 

  8. Marlow N, Wolke D, Bracewell MA, Samara M. Neurologic and developmental disability at six years of age after extremely preterm birth. N Engl J Med. 2005;352(1):9–19.

    CAS  PubMed  Google Scholar 

  9. Pappas A, Kendrick DE, Shankaran S, et al. Chorioamnionitis and early childhood outcomes among extremely low-gestational-age neonates. JAMA Pediatr. 2014;168(2):137–147.

    PubMed  PubMed Central  Google Scholar 

  10. van Vliet EO, de Kieviet JF, van der Voorn JP, Been JV, Oosterlaan J, van Elburg RM. Placental pathology and long-term neurodevelopment of very preterm infants. Am J Obstet Gynecol. 2012; 206(6):489 e1–7.

    Google Scholar 

  11. Smit AL, Stokroos RJ, Litjens SG, Kremer B, Kramer BW. Potential role for lipopolysaccharide in congenital sensorineural hearing loss. J Med Microbiol. 2010;59(Pt 4):377–383.

    CAS  PubMed  Google Scholar 

  12. Suppiej A, Franzoi M, Vedovato S, Marucco A, Chiarelli S, Zanardo V. Neurodevelopmental outcome in preterm histological chorioamnionitis. Early Hum Dev. 2009;85(3):187–189.

    PubMed  Google Scholar 

  13. Soraisham AS, Trevenen C, Wood S, Singhal N, Sauve R. Histological chorioamnionitis and neurodevelopmental outcome in preterm infants. J Perinatol. 2013;33(1):70–75.

    CAS  PubMed  Google Scholar 

  14. Hendson L, Russell L, Robertson CM, et al. Neonatal and neurodevelopmental outcomes of very low birth weight infants with histologic chorioamnionitis. J Pediatr. 2011;158(3):397–402.

    PubMed  Google Scholar 

  15. Smit AL, Been JV, Zimmermann LJ, et al. Automated auditory brainstem response in preterm newborns with histological chorioamnionitis. J Matern Fetal Neonatal Med. 2014;6:1–6.

    Google Scholar 

  16. Wollack C. The auditory acuity of the sheep (Ovis aries). J Audit Res. 1963;3:121–132.

    Google Scholar 

  17. Fay R, Popper A, eds. Comparative Hearing: Mammals. New York: Springer-Verlag; 1994.

    Google Scholar 

  18. Gavilanes AW, Gantert M, Strackx E, et al. Increased EEG delta frequency corresponds to chorioamnionitis-related brain injury. Front Biosci (Schol Ed). 2010;2:432–438.

    Google Scholar 

  19. Kuypers E, Collins JJ, Jellema RK, et al. Ovine fetal thymus response to lipopolysaccharide-induced chorioamnionitis and antenatal corticosteroids. PLoS One. 2012;7(5):e38257.

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Wolfs TG, Kallapur SG, Polglase GR, et al. IL-1alpha mediated chorioamnionitis induces depletion of FoxP3+ cells and ileal inflammation in the ovine fetal gut. PLoS One. 2011;6(3):e18355.

    CAS  PubMed  PubMed Central  Google Scholar 

  21. Collins JJ, Kuypers E, Nitsos I, et al. LPS-induced chorioamnionitis and antenatal corticosteroids modulate Shh signaling in the ovine fetal lung. Am J Physiol Lung Cell Mol Physiol. 2012; 303(9):L778–L787.

    CAS  PubMed  PubMed Central  Google Scholar 

  22. Kramer BW, Moss TJ, Willet KE, et al. Dose and time response after intraamniotic endotoxin in preterm lambs. Am J Respir Crit Care Med. 2001;164(6):982–988.

    CAS  PubMed  Google Scholar 

  23. Keogh MJ, Bennet L, Drury PP, et al. Subclinical exposure to low-dose endotoxin impairs EEG maturation in preterm fetal sheep. Am J Physiol Regul Integr Comp Physiol. 2012;303(3): R270-R278.

    CAS  PubMed  Google Scholar 

  24. Newnham JP, Moss TJ, Kramer BW, Nitsos I, Ikegami M, Jobe AH. The fetal maturational and inflammatory responses to different routes of endotoxin infusion in sheep. Am J Obstet Gynecol. 2002;186(5):1062–1068.

    CAS  PubMed  Google Scholar 

  25. Smit AL, Seehase M, Stokroos RJ, et al. Functional impairment of the auditory pathway after perinatal asphyxia and the short-term effect of perinatal propofol anesthesia in lambs. Pediatr Res. 2013;74(1):34–38.

    CAS  PubMed  Google Scholar 

  26. Sohmer H, Friedman I. Prolonged conductive hearing loss in rat pups causes shorter brainstem transmission time. Hear Res. 1992;61(1–2):189–196.

    CAS  PubMed  Google Scholar 

  27. Stockard JE, Stockard JJ, Westmoreland BF, Corfits JL. Brainstem auditory-evoked responses. Normal variation as a function of stimulus and subject characteristics. Arch Neurol. 1979;36(13): 823–831.

    CAS  PubMed  Google Scholar 

  28. Hall JW. ABR analysis and interpretation. In: Hall JW, ed. New Handbook of Auditory Evoked Responses. Boston: Pearson; 2006:212–257.

    Google Scholar 

  29. Ashwal S, Staddon T, Geller M, Longo LD. Brainstem auditory evoked responses in the newborn lamb. Studies during postnatal development and acute hypoxia. Biol Neonate. 1984; 45(2):58–68.

    CAS  PubMed  Google Scholar 

  30. Woods JR Jr, Plessinger MA. The fetal auditory brain stem response: serial measurements at two stimulus intensities. Otolaryngol Head Neck Surg. 1985;93(6):759–764.

    PubMed  Google Scholar 

  31. Anniko M, Hellstrom S, Schmidt SH, Spandow O. Toxic effects on inner ear of noxious agents passing through the round window membrane. Acta Otolaryngol Suppl. 1989;457:49–56.

    CAS  PubMed  Google Scholar 

  32. Suzuki M, Harris JP. Expression of intercellular adhesion molecule-1 during inner ear inflammation. Ann Otol Rhinol Laryngol. 1995;104(1):69–75.

    CAS  PubMed  Google Scholar 

  33. Gong S, Zeng X, Yan Z, Wang J. Expression of intercellular adhesion molecule-1 in immune response of inner ear. J Tongji Med Univ. 1998;18(4):208–211.

    CAS  PubMed  Google Scholar 

  34. Abbott NJ, Ronnback L, Hansson E. Astrocyte-endothelial interactions at the blood-brain barrier. Nat Rev Neurosci. 2006;7(1): 41–53.

    CAS  PubMed  Google Scholar 

  35. Laborada G, Nesin M. Interleukin-6 and interleukin-8 are elevated in the cerebrospinal fluid of infants exposed to chorioamnionitis. Biol Neonate. 2005;88(2):136–144.

    CAS  PubMed  Google Scholar 

  36. Griffiths SK, Pierson LL, Gerhardt KJ, Abrams RM, Peters AJ. Noise induced hearing loss in fetal sheep. Hear Res. 1994; 74(1–2):221–230.

    CAS  PubMed  Google Scholar 

  37. Jiang ZD, Brosi DM, Wilkinson AR. Comparison of brainstem auditory evoked responses recorded at different presentation rates of clicks in term neonates after asphyxia. Acta Paediatr. 2001; 90(12):1416–1420.

    CAS  PubMed  Google Scholar 

  38. Jiang ZD, Brosi DM, Shao XM, Wilkinson AR. Maximum length sequence brainstem auditory evoked responses in term neonates who have perinatal hypoxia-ischemia. Pediatr Res. 2000;48(5): 639–645.

    CAS  PubMed  Google Scholar 

  39. Amin SB, Wang H. Histologic chorioamnionitis and acute neurologic impairment in premature infants. J Matern Fetal Neonatal Med. 2010;23(10):1165–1171.

    PubMed  PubMed Central  Google Scholar 

  40. Mason JA, Herrmann KR. Universal infant hearing screening by automated auditory brainstem response measurement. Pediatrics. 1998;101(2):221–228.

    CAS  PubMed  Google Scholar 

  41. Boksa P. Effects of prenatal infection on brain development and behavior: a review of findings from animal models. Brain Behav Immun. 2010;24(6):881–897.

    PubMed  Google Scholar 

  42. Meyer U, Feldon J, Fatemi SH. In-vivo rodent models for the experimental investigation of prenatal immune activation effects in neurodevelopmental brain disorders. Neurosci Biobehav Rev. 2009;33(7):1061–1079.

    CAS  PubMed  Google Scholar 

  43. Meyer U, Feldon J, Yee BK. A review of the fetal brain cytokine imbalance hypothesis of schizophrenia. Schizophr Bull. 2009; 35(5):959–972.

    PubMed  Google Scholar 

  44. Rezaie P, Dean A. Periventricular leukomalacia, inflammation and white matter lesions within the developing nervous system. Neuropathology. 2002;22(3):106–132.

    PubMed  Google Scholar 

  45. Gavilanes AW, Strackx E, Kramer BW, et al. Chorioamnionitis induced by intraamniotic lipopolysaccharide resulted in an interval-dependent increase in central nervous system injury in the fetal sheep. Am J Obstet Gynecol. 2009;200(4):437 e1–8.

    Google Scholar 

  46. Kastenbauer S, Klein M, Koedel U, Pfister HW. Reactive nitrogen species contribute to blood-labyrinth barrier disruption in suppurative labyrinthitis complicating experimental pneumococcal meningitis in the rat. Brain Res. 2001;904(2):208–217.

    CAS  PubMed  Google Scholar 

  47. Ghiani CA, Mattan NS, Nobuta H, et al. Early effects of lipopolysaccharide-induced inflammation on foetal brain development in rat. ASN Neuro. 2011;3(4):233–245.

    CAS  Google Scholar 

  48. Ruebhausen MR, Brozoski TJ, Bauer CA. A comparison of the effects of isoflurane and ketamine anesthesia on auditory brainstem response (ABR) thresholds in rats. Hear Res. 2012;287(1–2):25–29.

    CAS  PubMed  Google Scholar 

  49. Stronks HC, Aarts MC, Klis SF. Effects of isoflurane on auditory evoked potentials in the cochlea and brainstem of guinea pigs. Hear Res. 2010;260(1–2):20–29.

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Adriana L. Smit MD.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Smit, A.L., Lambermont, V.A., Stokroos, R.J. et al. Intrauterine Lipopolysaccharide-Induced Chorioamnionitis in a Sheep: Does It Affect the Auditory System?. Reprod. Sci. 23, 257–263 (2016). https://doi.org/10.1177/1933719115602759

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1177/1933719115602759

Keywords

Navigation