Study Of Clinical Significance And Pathogenesis On Premature Aging Of Placenta

Although there is no definitive conception on placental senescence until today, it is widely believed that after 37 weeks in normal pregnancy the placenta progressively ages and has morphological and physiological senescence. Placental growth slows, even ceases during the last few weeks of gestation and the incidence of placental abnormalities , such as infarcts, calcification, basal membrane thicken , or massive perivillous fibrin deposition increase, often companied with placental function decline. These structural and functional changes of term placenta are often considered as placental aging.Premature aging of placenta means that placenta appears the aging change on structure before term. At the same time, placental functional capacity decline. This is usually diagnosed by appearance of grade Ⅲ placental maturation on ultrasonic image before 37 weeks of gestation. It is widely reported that pregnancies demonstrating grade Ⅲ maturational changes prior to 37 weeks, especially prior to 34 weeks, had significantly higher incidences of perinatal complications such as preeclampsia, oligohydramnios, fetal growth retardation et al. So preterm grade Ⅲ placenta is considered as a sensitive predictor of poor perinatal outcome. However, Pathological base and pathogensis of the ultrasonic appearance of premature aging of placenta are not still understood. It is important to find the relation among ultrasonicimage, placental function and pathological changes in premature aging of placenta and to explore it's pathogensis. This will help to prevent the occurrence and development of FGR and preeclamapsia.The strong echoes detected in the placenta by antenatal ultrasonic scan correspond to depositions of fibrin and calcium. Many studies indicated that apoptotic cells present in the placenta during the whole pregnant period. With the progression of pregnancy, the number of apoptotic cells increase significantly. More apoptotic cells appear in the case of pathologic pregnancies such as postterm pregnancy, FGR and preeclamapsia. Apoptosis within placenta is often related to fibrosis and calcification. It occurs before calcification and apoptosis body can become the core of calcification .On the other hand, the pregnant complications associated with the ultrasonic image of premature aging, such as FGR, preeclamapsia, have been proved to be related to imbalance between prostanoids. The imbalance between prostanoids can be detected two month before clinical symptom of the complications occurs. It mainly is the decrease of prostacyclin . Recent researches show that prostanoids not only can regulate vascular reactivity but also affect proliferation, differentiation and apoptosis of various cell types. It is known that thromboxane can inhibit differentiation and enhance apoptosis of cultured human trophoblasts, but the effect of prostacyclin on trophoblasts is unknown. In order to understand the pathological base under the aging image as well as the role of apoptosis and the decrease of prostacyclin on the pathogenesis of premature aging of placenta, we started this research.Methodsl.The perinatal outcomes of 54 pregnant women with prematurely aging placenta diagnosed ultrasonographically were analyzed retrospectively in Nanfanghospital from January 2000 to May 2005, and 248 pregnant women without prematurely aging placenta diagnosed ultrasonographically during the period were selected at random to serve as control. The gestational ages and the incidences of pregnant complications such as preeclampsia ,FGR, SGA and oligohydrmnios were compared in the two groups.For analysis of birth weight and Apgar scores,each patient in the group with prematurely aging placenta was randomly matched with two normally pregnant woman who had deliveried by the same mean of delivery at the same gestational week.For analysis of the concentration of E3 in mothern blood and the Doppler indices of blood stream of umbilical artery, each patients in the group with prematurely aging placenta was randomly matched with one normally pregnant women who had detected either of the two tests at the same gestational week2. The placental samples were collected immediately after delivery from 15 pregnant women with prematurely aging placenta diagnosed ultrasonographically and 15 normally pregnant women gestational-matched. All these pregnant women received prenatal care and had their babies deliveried at Nanfan hospital and the second people hospital of Guangzhou during the period of September 2003 ~ December2000.The sample were examined with hematoxylin-eosin staining.The volum density of villi , villous capillary , and intervillous interval were measured and calculated by computer image analyzing software Q500MC which was made in German 4.3.The expression of HPL in placental samples was detected using immunohistochemical assay. Those stained sections were evaluated by the semiquantitative immunohistochemical scoring system.4.Apoptosis was analyzed by terminal deoxynucleotidyl transferase deoxyuridine triphosphaste nicked-end labeling staining(TUNEL) and the percentage of apoptosis nuclei were counted.5.Tissue- predigest- cell- culture- method was used to get the trophoblastic cells and their purity was identified by immunocytochemistry with specific monoclonal antibody to cytokerratin 7. The cells cultured for 6 days were incubated with different concentration of iloprost ( a stable analog of PGI2). The concentration of HPL in media cultured for 24 hours and 48 hours was determined by a radioimmunoassay method. After co-cultured for 48 hours, these cells were collected and apoptotic cells was detected by flow cytometry and TUNEL stainingAll data were analyzed by statistical analysis with SPSS 11.0 statistic software. ResultThe incidence of pregnant complications was significanctly higher for the study than for the control( 44.44% versus 22.17 %;P<0.001=,as were the incidences of oligohydrmnios,preeclampsiaand and SGA ( 25.93%,12.96%andl6.67% versus8.87%,1.61% and 4.84%;P<0.05=. Gestational age of the studied group were significantly lower than those in the control group[(37. 26 ±2.08) week versus (39. 27 ±2.11) week] .New birth weight of prenant women in study group was significantly heavier than that of matched control women[ (2769.81 ±561. 30) g verse (2941.96+460) g, P<0. 05]2 The pulsatility index (PI) and the ratio of peak systolic to lowest diastolic flow velocity (S/D) in umbilical artery were significance higher for the study group than for the control[ (0.79+0.15) vs (0.71±0.09) P<0.05] and [ (2.33+0.38) vs (2.00 +0.17) ,P<0.001].2. Placental tissue studied showed apparently pathological change of placental senescence such as increase of fibrosis and calcification of villis strom, villous fibrinoid necrosis, villou syncytial knots et al. The volume density of villous capillaries were significantly decreased in the studied group [ (23. 57 +1.14) vs(25. 78 ±1. 55) , P<0. 01]], The volume density of intervillis space were also siginificently reduced [ (38. 98 ± 6. 39 ) vs ( 55. 41 ± 6. 95), P<0. 001], but there were not significant difference in the volume density of villis in two groups. [ (49. 31 ± 13.56) vs(50. 84±14. 56 ),P>0. 05],3.There was no difference in the expression of HPL in placentas and the concentration of E3 in mothern blood between groups [20. 87(15. 44, 24. 92) vs 19.61 (18. 32, 20. 67), P > 0.05] and [7. 95(4. 7,12. 25)ng/ml vs 8. 7(5. 45,11. 65)ng/ml, P>0. 05]4.The percentage of apoptotic cells in premature aging placentas was significantly higher than, in controls [0. 42 (0. 29, 0. 74) vs 0.23(0.12,0.27), P<0. 001]5.The experiment of placental cell culture showed that PGI2 can promote the secretion of HPL of trophoblasts and inhibit their apoptosis. Conclusionl.The ultrasonic appearance of premature aging placenta is associated with poor pregnant outcomes.2.The tissue structure of the premature aging placentas was damaged. Their active tissue structure decreased and blood stream of umbilical artery was reduced .All these changes may contribute to the increase of pregnant complications in them..3. The expression of HPL in placentas and the concentration of E3 in mothern blood in the studied didn't significantly declined,which indicates prematurely aging placenta has still enough capability to compensate the damaged structure.4.Apoptotic index in premature aging placentas increased. This indicated apoptosis increase may be one of the pathogenesis of premature aging of placenta. Prostacyclin can inhibit trophoblastic apoptosis and accelerate the secretion of HPL,which indicates that PGI2 can protect term human trophoblasts from apoptosis. In the premature aging placenta, apoptosis increases and the secretion of HPL decreases. All these show that prostacyclin decrease may be one of pathogenesis of premature aging placenta...