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Endothelia of term human placentae display diminished expression of tight junction proteins during preeclampsia

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Abstract

This study explores the molecular composition of the tight junction (TJ) in human term placenta from normal women and from patients with preeclampsia, a hypertensive disorder of pregnancy. Maternal endothelial dysfunction is a critical characteristic of preeclampsia; hence, we have analyzed its impact on placental vessels. The study concentrates on the TJ because this structure regulates the sealing of the paracellular route. We have found that, in placental endothelial vessels, TJ components include the peripheral protein ZO–1 and the integral proteins occludin and claudins 1, 3, and 5. During preeclampsia, the amounts of occludin and ZO–1 exhibit no significant variation, whereas those of claudins 1, 3, and 5 diminish, suggesting the presence of leakier TJs in the endothelia of the preeclamptic placenta, possibly in response to the decreased perfusion of this organ during preeclampsia. We have unexpectedly found that, in normal placentae, the multinucleated syncytiotrophoblast layer displays claudin 4 at the basal surface of the plasma membrane, and claudin 16 along the apical and basolateral surfaces. The presence of membrane-lined channels that cross the syncytiotrophoblast constituting a paracellular pathway has been determined by transmission electron microscopy and by the co-immunolocalization of claudin 16 with the plasma membrane proteins Na+K+-ATPase and GP135. Since claudin 16 functions as a paracellular channel for Mg2+, its diffuse pattern in preeclamptic placentae suggests the altered paracellular transport of Mg2+ between the maternal blood and the placental tissue.

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Acknowledgement

We thank Dr. Oscar Arturo Martinez Rodriguez, Director of the Gynecological Hospital of La Raza Medical Center-IMSS in Mexico City, for his help in obtaining the placentae. This work was submitted in partial fulfilment of the requirements for the PhD degree awarded to Samuel Liévano (Doctorate in Biomedical Science of the National Autonomous University of Mexico; UNAM).

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Authors and Affiliations

  1. Gynecology and Obstetrics Hospital, La Raza Medical Center, Mexican Institute of Social Security (IMSS), México D.F., Mexico

    Samuel Liévano

  2. Department of Physiology, Biophysics and Neuroscience, Center for Research and Advanced Studies (CINVESTAV), Ave. Politécnico Nacional 2508, México D.F., 07360, Mexico

    Lourdes Alarcón & Lorenza González–Mariscal

  3. Department of Experimental Pathology, CINVESTAV, México D.F., Mexico

    Bibiana Chávez–Munguía

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  1. Samuel Liévano
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  2. Lourdes Alarcón
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  3. Bibiana Chávez–Munguía
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  4. Lorenza González–Mariscal
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Correspondence to Lorenza González–Mariscal.

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This work was supported by grants 45691-Q from the Mexican Council for Science and Technology (CONACYT) and 2005/1/I/012 from the Research Promotion Fund of the Mexican Institute of Social Security (IMSS/FOFOI).

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Liévano, S., Alarcón, L., Chávez–Munguía, B. et al. Endothelia of term human placentae display diminished expression of tight junction proteins during preeclampsia. Cell Tissue Res 324, 433–448 (2006). https://doi.org/10.1007/s00441-005-0135-7

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