Placental protein 13 and decidual zones of necrosis: an immunologic diversion that may be linked to preeclampsia.

We evaluated the role of placental protein 13 (PP13; galectin 13) in the process of trophoblast invasion and decidual necrosis. Immunohistochemical analysis for PP13, immune cells, human placental lactogen, cytokeratin, and apoptosis markers was performed on 20 elective pregnancy termination specimens between 6 and 15 weeks of gestation. Placental protein 13 was localized to syncytiotrophoblasts in the chorionic villi and to occasional multinucleated luminal trophoblasts within converted decidual spiral arterioles. Cytotrophoblasts, anchoring trophoblasts, and invasive trophoblasts did not stain for PP13. Extracellular PP13 aggregates were found around decidual veins associated with T-cell-, neutrophil- and macrophage-containing decidual zones of necrosis (ZONEs). We hypothesize that PP13 is secreted into the intervillus space, drains through the decidua basalis veins, and forms perivenous PP13 aggregates which attract and activate maternal immune cells. Thus, syncytiotrophoblast-derived PP13 may create a ZONE that facilitates trophoblast invasion and conversion of the maternal spiral arterioles.

Effects of calcium, magnesium, low-dose aspirin and low-molecular-weight heparin on the release of PP13 from placental explants.

BACKGROUND: Preeclampsia is one of the leading causes for maternal and fetal morbidity. Attempts to prevent preeclampsia have already been made using low-dose aspirin, low-molecular-weight heparin (LMWH), and calcium supplementation. Magnesium sulphate is used at the time of disease to prevent eclampsia. Here we investigated the effect of these agents on PP13 release from placental explants. METHODS: Placentas harvested after C-section of term or preterm control and preeclampsia cases or first trimester terminations were used to obtain explants. Explants were incubated for 24h with/without respective agents, harvested, weighed and subjected to PP13 determination in the culture medium and the explant. LDH was used to determine viability. Dose response curves were obtained for each drug. P < 0.05 was considered significant. RESULTS: Exposure to magnesium (0.7-7g/day) slightly decreased PP13 release from controls, and slightly increased it in preeclampsia and first trimester termination. Calcium (0. 3-6g/day) showed a tendency to decrease the release in control and preeclampsia, whereas in first trimester release was increased in a bell-shaped manner. Aspirin (0-250 mg/day) tended to decrease the release in controls but increased it in a bell-shaped manner in first trimester and preeclampsia. LMWH showed no effect from 0 to 80 mg/day in controls but tended to decrease PP13 release in preeclampsia and first trimester. CONCLUSION: This data might point to a beneficial effect of aspirin and calcium supplementation in the first trimester of pregnancy and aspirin at the time of disease, although the interaction with the maternal system still needs to be elucidated.

Placental protein 13 as an early marker for pre-eclampsia: a prospective longitudinal study.

OBJECTIVE: To assess the value of placental protein 13 (PP13) as an early marker of pre-eclampsia. DESIGN: Sequential blood samples were obtained from women with singleton viable pregnancies at 6-10, 16-20 and 24-28 weeks of gestation. Samples were tested for PP13 using a solid-phase sandwich enzyme-linked immunosorbent assay. Levels were expressed as multiples of the medians (MoM) of the unaffected population. The slope or rate of change in PP13 concentration per week of gestation was also calculated. SETTING: Thirty-five prenatal care community clinics. SAMPLE: In total, 1,366 women were recruited, and subsequently, 20 were diagnosed with pre-eclampsia, 41 with gestational hypertension and 1,178 were unaffected. MAIN OUTCOME MEASURES: Sensitivity and specificity of screening with PP13 at each gestational period and of PP13 level combined with the slope of PP13 between two testing periods. RESULTS: At 6-10 gestational weeks, PP13 levels were significantly lower among the pre-eclampsia group with a median 0.28 MoM (95% CI 0.15-0.39, P < 0.004). Using a cutoff of 0.40 MoM, the sensitivity was 80%, false-positive rate (FPR) was 20% and odds ratio was 16.0 (95% CI 5.3-48.4). Combining MoM of 6-10 weeks and slope between 6-10 and 16-20 weeks, the sensitivity was 78%, the FPR was 6% and odds ratio was 55.5 (95% CI 18.2-169.2). The gestational hypertension group was not different from the normal group. CONCLUSIONS: PP13 in the first trimester alone or in combination with the slope between the first and the second trimesters may be a promising marker for assessing the risk of pre-eclampsia.