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Chorioamnionitis and preeclampsia account for the majority of preterm births worldwide. Thus far, adequate methods for early detection or prevention of these diseases are lacking. In preeclampsia, accelerated villous maturation is believed to compensate placental insufficiency. However, little is known about the effects of placental inflammation in chorioamnionitis on villous maturation. Therefore, we established a set of morphological parameters to evaluate histological villous maturity in pregnancies complicated by chorioamnionitis and preeclampsia. Preterm placentas complicated by chorioamnionitis or preeclampsia were compared to idiopathic preterm placentas and term controls. Histological villous maturation was analyzed by means of 17 histological markers. Fourteen of these markers provided information on absolute and relative numbers of the terminal villi (TV), the extent of their vascularization (using CD31-stained sections) and their exchange capacities. In addition, the numbers of syncytial bridges, syncytial apoptotic knots and shed syncytiotrophoblasts were counted. Accelerated villous maturation in preeclampsia was demonstrated by means of histological villous remodeling and confirmed by 11 relevant markers. Chorioamnionitis, however, only showed increased area of fetal capillaries. In preeclampsia, placentas may transition from growth to maturation earlier than placentas in normal pregnancies, whereas in chorioamnionitis placental changes are more acute and therefore less elaborated at a structural level. Regression analysis suggests the number of all villi and the number of terminal villi as a percentage of all villi as parameters to evaluate histological villous maturity in preeclamptic placentas and to assist diagnosis. However, we would recommend to analyze all 11 relevant parameters to judge placental maturity in detail.

Optimale feto-maternale gas en nutriënten uitwisseling gaat via placental terminale villi (TV) dat bevat fetal capillairen (FC) met vasculo-syncytial membranes(VSM) waar diffusie ten hoogste is. TV maturiteit is verstoord bij preeclampsie (PE) en chorioamnionitis (CA). In de eerste cohort van normale vroeg- (control) en tijdig-geboren (Term), en CA of PE (n=6/groep), wilde wij eerder verkregen resultaten valideren en inter-observer variatie evalueren. In de tweede cohort (PE and control,n=10/groep), toetste wij welke van CD31 of CD34 endothelial merker better is. In eerste en tweede cohort placentas gekleurd voor CD31 or CD34 en hematoxylin/eosine werd 18 placental maturiteit parameters gemeten: %, oppervlakte en omtrek van TV en FC; VSM lengte en diffusie afstand. The Bland-Altman gevolgd door One sample t-test zijn gebruikt voor inter-observer variatie analyse. Met One-way ANOVA of Wilcoxon Signed-rank test, worden de resultaten van de eerste en tweede cohort getoetst. Preesclampsia placentas had verhoogde foetale capillaires dan control. De resultaten uit de eerder gemaakte analyse kon worden bevestigd [P > 0.05 voor 16 parameters in control. Bij andere groepen, kreeg wij een inter-observer variatie bij de volgende parameters: %TV (P=0.007 voor PE en P=0.05 voor CA);voor PE de TV omtrek van (P=0.04), oppervlakte van FC (P=0.04) en de percentage van de oppervlakte van FC (P=0.02); de oppervlakte TV (P=0.02) en de omtrek FC (0.004) voor groep Term]. Endothelial CD31 and CD34 kleuringen gave vergelijkbaar resultaten.

Haptoglobin is an acute phase protein that can be divided into the phenotypes Hp 1 1, Hp 2 1 and Hp 2 2 by different alpha-unities. The main function of haptoglobin is binding of free hemoglobin, however, in the meantime it appears, that in addition it has immunmodulatory properties and modulates lymphocyte and monocyte immune answer (Sadrzadeh and Bozorgmehr 2004). Haptoglobin also influences decidual lymphocytes and their cytokine expression (von Rango 2005). Thereby it is significant for the development of pregnancy which involves important immunological processes (Nauta 2006). The aim of this work was, to analyze haptoglobin protein and mRNA expression by means of PCR, Western blot and immunohistochemistry within the female cycle and the early pregnancy in humans. Moreover, a possible connection between fecundity and the haptoglobin phenotype was examined. Finally, the haptoglobin production was compared in different tissues to rank the expression in endometrium and decidua quantitatively. Haptoglobin mRNA and protein expression could be shown during the whole menstrual cycle. It was predominantly expressed within the stroma. Haptoglobin mRNA as well as the protein expression decreased with the beginning luteal phase and reincreased at the time of a possible implantation, suggesting a specific regulation and function of the haptoglobin in this period. Haptoglobin was also found to be expressed continuously in the early pregnancy up to the 16th pregnancy week. The expression was high at the time of the strongest extravillous trophoblast invasion in the first trimester. With the beginning of the second trimester expression decreased, then the mRNA and protein expression rose again clearly. The immunohistochemistry showed a clear haptoglobin expression in the glandular epithelium and in the stroma. During pregnancy maternal rejection of the embryo must be prevented. At the time of the implantation and in the early pregnancy many leucocytes migrate into the uterine wall. There haptoglobin may exert its function. Haptoglobin restrains antibody activation and proliferation/activation of T-lymphocytes (Oh et al. 1987, Arredouani et al. 2003, Frings et al. 2002). Furthermore, it prevents the migration of macrophages and B-cells in inflammatory tissue (Hanasaki et al. 1995, Nauta et al. 2006) and increases the expression of antiinflammatory cytokines (Arredouani et al. 2001). Thus haptoglobin can suppress a possible immune answer. The exact timing of haptoglobin expression in the female reproductive tract supposes an influence of haptoglobin on the immunological processes during a pregnancy. No significant difference was found concerning the haptoglobin phenotype and genotype between fertile and infertile women. The analysis of haptoglobin mRNA expression in different tissues showed that beside the predominant expression site the liver a high expression could be found also in reproductive organs like ovaries, tubes and testicles. In the endometrium Haptoglobin expression was clearly low, nevertheless, at the beginning of pregnancy expression strongly increased. This also points to the fact that haptoglobin function is important for the success of pregnancy.