Skip to main content

Advertisement

SpringerLink
Log in

Food allergens are transferred intact across the rat blood-placental barrier in vivo

  • Original Paper
  • Published:
Medical Molecular Morphology Aims and scope Submit manuscript

Abstract

We investigated the mechanism of transplacental macromolecular transport in rats on the nineteenth day of pregnancy using tracers, transmission electron microscopy and immunohistochemistry. The blood-placental barrier of full-term rat placentas was composed of a trilaminar layer of trophoblast cells that separates the fetal capillaries from the maternal blood spaces: a layer of cytotrophoblasts lining the maternal blood space and a bilayer of syncytiotrophoblast surrounding the fetal capillaries. Horseradish peroxidase, intravenously injected into the maternal circulation, was found in the maternal blood spaces, the interspaces between the cytotrophoblasts and the syncytiotrophoblast I, many pits and small vesicles in the syncytiotrophoblast I, vesicles of the syncytiotrophoblast II, fetal connective tissue and fetal capillaries. Intravenously injected ovalbumin was detected in the maternal blood spaces, a trilaminar layer and the fetal capillaries. Neonatal Fc receptor (FcRn), a receptor for IgG, was localized at the maternal side of the blood-placental barrier. These results show that the structure of the rat blood-placental barrier is quite similar to the human blood-placental barrier, and non-specific macromolecules and food allergens may penetrate through the blood-placental barrier of the full-term placenta from the maternal to fetal circulation mediated by FcRn.

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

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Chan-Yeung M, Ferguson A, Chan H, Dimich-Ware H, Watson W, Manfreda J, Becker A (1999) Umbilical cord blood mononuclear cell proliferative response to house dust mite does not predict the development of allergic rhinitis and asthma. J Allergy Clin Immunol 104:317–321

    Article  CAS  PubMed  Google Scholar 

  2. Marks GB, Zhou J, Yang HS, Joshi PA, Bishop GA, Britton WJ (2002) Cord blood mononuclear cell cytokine responses in relation to maternal house dust mite allergen exposure. Clin Exp Allergy 32:355–360

    Article  CAS  PubMed  Google Scholar 

  3. Smillie FI, Elderfield AJ, Patel F, Cain G, Tavenier G, Brutsche M, Craven M, Custovic A, Woodcock K (2001) Lymphoproliferative responses in cord blood and at one year: no evidence for the effect of in utero exposure to dust mite allergens. Clin Exp Allergy 31:1194–1204

    Article  CAS  PubMed  Google Scholar 

  4. Vance GH, Lewis SA, Grimshaw KE, Wood PJ, Briggs RA, Thornton CA, Warner JO (2005) Exposure of the fetus and infant to hens’ egg ovalbumin via the placenta and breast milk in relation to maternal intake of dietary egg. Clin Exp Allergy 35:1318–1326

    Article  CAS  PubMed  Google Scholar 

  5. Edelbauer M, Loibichler C, Witt A, Gerstmayr M, Putschögl B, Urbanek R, Szépfalusi Z (2003) Dose-dependent and preterm-accentuated diaplacental transport of nutritive allergens in vitro. Int Arch Allergy Immunol 130:25–32

    Article  PubMed  Google Scholar 

  6. Szépfalusi Z, Loibichler C, Hänel-Dekan S, Dehlink E, Gerstmayr M, Pichler J, Eiwegger T, Horvat R, Urbanek R (2006) Most of diaplacentally transferred allergen is retained in the placenta. Clin Exp Allergy 36:1130–1137

    Article  PubMed  Google Scholar 

  7. Edwards D, Jones CJ, Sibley CP, Nelson DM (1993) Paracellular permeability pathways in the human placenta: a quantitative and morphological study of maternal–fetal transfer of horseradish peroxidase. Placenta 14:63–73

    Article  CAS  PubMed  Google Scholar 

  8. Brownbill P, Edwards D, Jones C, Mahendran D, Owen D, Sibley C, Johnson R, Swanson P, Nelson DM (1995) Mechanisms of alphafetoprotein transfer in the perfused human placental cotyledon from uncomplicated pregnancy. J Clin Invest 96:2220–2226

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  9. Nishikawa M, Iwano H, Yanagisawa R, Koike N, Inoue H, Yokota H (2010) Placental transfer of conjugated bisphenol A and subsequent reactivation in the rat fetus. Environ Health Perspect 118:1196–1203

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  10. Roopenian DC, Akilesh S (2007) FcRn: the neonatal Fc receptor comes of age. Nat Rev Immunol 7:715–725

    Article  CAS  PubMed  Google Scholar 

  11. Leach JL, Sedmak DD, Osborne JM, Rahill B, Lairmore MD, Andeeson CL (1996) Isolation from human placenta of the IgG transporter, FcRn, and localization to the syncytiotrophoblast: implications for maternal–fetal antibody transport. J Immunol 157:3317–3322

    CAS  PubMed  Google Scholar 

  12. Rath T, Kuo TT, Baker K, Qiao SW, Kobayashi K, Yoshida M, Roopenian D, Fiebiger E, Lencer WI, Blumberg RS (2012) The immunologic functions of neonatal Fc receptor for IgG. J Clin Immunol [Epub ahead of print]

  13. Simister NE (2003) Placental transport of immunoglobulin G. Vaccine 28:3365–3369

    Article  Google Scholar 

  14. Kristoffersen EK, Matre R (1996) Co-localization of the neonatal Fc gamma receptor and IgG in human placental term syncytiotrophoblasts. Eur J Immunol 26:1668–1671

    Article  CAS  PubMed  Google Scholar 

  15. Nakata K, Kobayashi K, Ishikawa Y, Yamamoto M, Funada Y, Kotani Y, Blumberg RS, Karasuyama H, Yoshida M, Nishimura Y (2010) The transfer of maternal antigen-specific IgG regulates the development of allergic airway inflammation early in life in an FcRn-dependent manner. Biochem Biophys Res Commun 395:238–243

    Article  CAS  PubMed  Google Scholar 

  16. Watson ED, Cross JC (2005) Development of structures and transport functions in the mouse placenta. Physiology (Bethesda) 20:180–193

    Article  CAS  Google Scholar 

  17. Maltepe E, Bakardjiev AI, Fisher SJ (2010) The placenta: transcriptional, epigenetic, and physiological integration during development. J Clin Invest 120:1016–1025

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  18. El-Hashash AH, Warburton D, Kimber SJ (2010) Genes and signals regulating murine trophoblast cell development. Mech Dev 127(1–2):1–20

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  19. Adamson SL, Lu Y, Whiteley KJ, Holmyard D, Hemberger M, Pfarrer C, Cross JC (2002) Interactions between trophoblast cells and the maternal and fetal circulation in the mouse placenta. Dev Biol 250:358–373

    Article  CAS  PubMed  Google Scholar 

  20. Ain R, Canham LN, Soares MJ (2003) Gestation stage-dependent intrauterine trophoblast cell invasion in the rat and mouse: novel endocrine phenotype and regulation. Dev Biol 260:176–190

    Article  CAS  PubMed  Google Scholar 

  21. Coan PM, Conroy N, Burton GJ, Ferguson-Smith AC (2006) Origin and characteristics of glycogen cells in the developing murine placenta. Dev Dyn 235:3280–3294

    Article  CAS  PubMed  Google Scholar 

  22. Pijnenborg R, Vercruysse L (2010) Animal models of deep trophoblast invasion. In: Pijinenborg R, Brosens I, Romero R (eds) Placental bed disorders. Cambridge University Press, Cambridge, pp 127–139

    Chapter  Google Scholar 

  23. Jacob HJ, Lazer J, Dwinell MR, Moreno C, Geurts AM (2010) Gene targeting in the rat: advantages and opportunities. Trends Genet 26:510–518

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  24. Furukawa S, Hayashi S, Usuda K, Abe M, Hagio S, Ogawa I (2011) Toxicological pathology in the rat placenta. J Toxicol Pathol 24:95–111

    Article  PubMed Central  PubMed  Google Scholar 

  25. Soares MJ, Chakraborty D, Karim Rumi MA, Konno T, Renaud SJ (2012) Rat placentation: An experimental model for investigating the hemochorial maternal–fetal interface. Placenta 33:233–243

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  26. Jacob HJ, Kwirwk AE (2002) Rat genetics: attaching physiology and pharmacology to the genome. Nat Rev Genet 3:33–42

    Article  CAS  PubMed  Google Scholar 

  27. Shin BC, Fujikura K, Suzuki T, Tanaka S, Takata K (1997) Glucose transporter GLUT3 in the rat placental barrier: a possible machinery for the transplacental transfer of glucose. Endocrinology 138:3997–4004

    Article  CAS  PubMed  Google Scholar 

  28. Metz J, Aoki A, Forssmann WG (1978) Studies on the ultrastructure and permeability of the hemotrichorial placenta. I. Intercellular junctions of layer I and tracer administration into the maternal compartment. Cell Tissue Res 192:391–407

    Article  CAS  PubMed  Google Scholar 

  29. Aoki A, Metz J, Forssmann WG (1978) Studies on the ultrastructure and permeability of the hemotrichorial placenta. II. Fetal capillaries and tracer administration into the fetal blood circulation. Cell Tissue Res 192:409–422

    Article  CAS  PubMed  Google Scholar 

  30. Kawahata K, Takahashi J, Yasuda Y, Tanimura I (1990) Studies on the ultrastructure and polystyrene particle permeability of trophoblastic layers in the rat placenta. Jpn J Zootech Sci 61:433–437

    Google Scholar 

  31. Hu D, Cross JC (2010) Development and function of trophoblast giant cells in the rodent placenta. Int J Dev Biol 54:341–354

    Article  CAS  PubMed  Google Scholar 

  32. Van der Aa EM, Peereboom-Stegeman JH, Noordhoek J, Gribnau FW, Russel FG (1998) Mechanisms of drug transfer across the human placenta. Pharm World Sci 20:139–148

    Article  PubMed  Google Scholar 

  33. Takizawa T, Anderson CL, Robinson JM (2005) A novel Fc gamma R-defined, IgG-containing organelle in placental endothelium. J Immunol 175:2331–2339

    CAS  PubMed  Google Scholar 

  34. Israel EJ, Patel VK, Taylor SF, Marshak-Rothstein A, Simister NE (1995) Requirement for a beta 2-microglobulin-associated Fc receptor for acquisition of maternal IgG by fetal and neonatal mice. J Immunol 154:6246–6251

    CAS  PubMed  Google Scholar 

  35. Hatae T, Fujita M, Sagara H (1986) Helical structure in the apical tubules of several absorbing epithelia. Kidney proximal tubule, visceral yolk sac and ductuli efferentes. Cell Tissue Res 244:39–46

    Article  CAS  PubMed  Google Scholar 

  36. Kim J, Mohanty S, Ganesan LP, Hua K, Jarjoura D, Hayton WL, Robinson JM, Anderson CL (2009) FcRn in the yolk sac endoderm of mouse is required for IgG transport to fetus. J Immunol 182:2583–2589

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  37. Catunda Lemos AP, Cervenak J, Bender B, Hoffmann OI, Baranyi M, Kerekes A, Farkas A, Bosze Z, Hiripi L, Kacskovics I (2012) Characterization of the rabbit neonatal Fc receptor (FcRn) and analyzing the immunophenotype of the transgenic rabbits that overexpresses FcRn. PLoS One 7:e28869

    Article  PubMed Central  PubMed  Google Scholar 

  38. Kumagai N, Baba R, Sakuma Y, Arita K, Shinohara M, Kourogi M, Fujimoto S, Fujita M (2011) Origin of the apical transcytic membrane system in jejunal absorptive cells of neonates. Med Mol Morphol 44:71–78

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

We thank Dr. Nana Kumagai for her skillful technical assistance. This study was supported in part by a Grant-in-Aid for Scientific Research (KAKENHI) from the Ministry of Education, Science, Sports, and Culture of Japan (RB, HM and MF).

Author information

Authors and Affiliations

  1. Graduate School of Health and Nutrition Sciences, Nakamura Gakuen University, 5-7-1 Befu, Jyonan-ku, Fukuoka, 814-0198, Japan

    Yoshiko Sakuma, Kumi Arita & Mamoru Fujita

  2. Department of Anatomy, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan

    Ryoko Baba & Hiroyuki Morimoto

  3. Faculty of Medicine, School of Nursing, Fukuoka University, Fukuoka, Japan

    Yoshiko Sakuma & Kumi Arita

Authors
  1. Yoshiko Sakuma
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ryoko Baba
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kumi Arita
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Hiroyuki Morimoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Mamoru Fujita
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Mamoru Fujita.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sakuma, Y., Baba, R., Arita, K. et al. Food allergens are transferred intact across the rat blood-placental barrier in vivo. Med Mol Morphol 47, 14–20 (2014). https://doi.org/10.1007/s00795-013-0029-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00795-013-0029-9

Keywords

Search

Navigation