Placental barrier breakage in preeclampsia: ultrastructural evidence I. de Luca Brunori a,b,* , L. Battini c,d , E. Brunori c,d , P. Lenzi c,d , A. Paparelli c,d , M. Simonelli c,d , V. Valentino c,d , A.R. Genazzani c,d a Department of Reproductive Medicine and Child Development, University of Pisa, S. Chiara Hospital, Via Roma 55, Pisa 56100, Italy b Lung’Arno Simonelli 3, Pisa 56100, Italy c Department of Human Morphology and Applied Biology, University of Pisa, S. Chiara Hospital, Via Roma 55, Pisa 56100, Italy d Stella Maris Foundation IRCCS, University of Pisa, S. Chiara Hospital, Via Roma 55, Pisa 56100, Italy Accepted 8 April 2004 Abstract Objective: It is known that the placenta acts as an immunological barrier between the mother and fetal ‘‘graft’’ allowing two antigenically different organisms to tolerate one another. Preeclampsia may be considered as a fetal rejection consequent to severe damage at placental endothelial and syncytiotrophoblast level. In order to verify this placental barrier damage we undertook the present study by electron microscopy. Study design: 14 placentae from preeclaptic women, and the same number of placentae from healthy controls were examined. Results: The results showed that endothelial cells from preeclamptic placentae express various and severe alterations, consisting of swollen and bulbous cytoplasm, degenerated inter-endothelial junctions with consequent crossing of fetal blood cells outside the vessels. Conclusions: These lesions could be the ultrastructural evidence of the placental barrier breakage leading to rejective reaction we presumed to be basis of preeclampsia. # 2004 Elsevier Ireland Ltd. All rights reserved. Keywords: Preeclampsia; Placental ultrastructure; Electron microscopy; HLA-DR 1. Introduction Preeclampsia is a severe gestational pathology, more common in primigravidae, which represents a danger both for the mother and her fetus. The aetiology of this pathol- ogy is still undefined, although it is generally accepted that implantation, which is an outstanding example of succes- sive interactions between two genetically distinct tissues [1,2], is impaired in preeclampsia. In fact, an abnormal trophoblastic invasion occurs in early pregnancy [3,4] and later, the placental endothelial cells dysfunction is accepted to be the common pathophysiological factor observed in preeclampsia [5–8]. This endothelial cell dysfunction is both apparant from morphological para- meters, e.g. endotheliosis and ultrastructural changes in placental bed and uterine boundary vessels [9,10], and biochemical parameters, e.g. a disturbance of the prostacyclin/thromboxane A 2 balance [5], and increase of V-CAM-1 plasmatic levels [11]. The placenta acts as an immunological barrier between the mother and the fetal ‘‘graft’’, allowing two antigenically different organisms to tolerate one another. During the course of pregnancy this barrier becomes extremely thin, less than 2 mm at term, which is only slightly greater than the pulmonary alveolar blood/air barrier [12]. It is clear that any damage to this barrier from various ischemic risk factors (metabolic, hormonal, genetic, immnological) may be responsible for lesions of the syncytiothrophoblast and villous vessels endothelial cells [13]. In this condition a mixing of maternal and fetal blood is possible with trigger- ing of a maternal rejective reaction as we hypothesised by using immunohistochemical technique and HLA-DR mono- clonal antibody. In particular we demonstrated an intense and widespread HLA-DR expression in the villous stroma of preeclamptic placentae [14]. To verify if the hypothesis of preeclampsia as a fetal rejection, which we followed according to different authors [3,15,16], could be supported by an ultrastructural evidence of the placental endothelial and syncytial damage, we undertook the current case-control study by electron micro- scopy in placentae from preeclamptic and physiological pregnancies. European Journal of Obstetrics & Gynecology and Reproductive Biology 118 (2005) 182–189 * Corresponding author. Tel.: þ39 050 42335; fax: þ39 050 42335. E-mail address: delucabrunori@hotmail.com (I. de Luca Brunori). 0301-2115/$ – see front matter # 2004 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ejogrb.2004.04.024