Hanping Chen

Reduced plasma adiponectin and elevated leptin in pre-eclampsia

Objective: To clarify the role of adipocytokine, adiponectin, and leptin in the pathogenesis of pre‐eclampsia (PE) and determine the relationships between plasma adiponectin and leptin levels. Method: A total of 73 women in the third trimester of pregnancy were recruited, 53 women with PE (study patients) and 20 age‐ and BMI‐matched normotensive women (healthy controls). They were divided into 3 groups: the 20 normotensive pregnant women (group 1); 32 women with mild pre‐eclampsia (group 2); and 21 women with severe pre‐eclampsia (group 3). The plasma levels of adiponectin and leptin are measured simultaneously and their correlation and balance were evaluated by enzyme‐linked immunosorbent assay. Results: Compared with controls, levels of adiponectin were significantly lower in women with mild or severe PE (P < 0.01 for both groups) whereas levels of leptin were significantly higher in women with mild or severe PE (P < 0.05 and P < 0.01, respectively). There was a negative correlation between plasma levels of adiponectin and leptin in pre‐eclamptic women (r = − 0.76, P < 0.01). Moreover, the adiponectin level to leptin level ratio was significantly lower in pre‐eclamptic women than that in healthy controls (P < 0.01). In the pre‐eclamptic women serum levels of triglycerides, total cholesterol and low‐density lipoprotein cholesterol were significantly increased (P < 0.01 for all), while high‐density lipoprotein cholesterol was significantly decreased compared to levels in normotensive pregnant women (P < 0.01). Conclusions: These findings suggest that there is an imbalance between adiponectin and leptin in the plasma of pre‐eclamptic women. Reduced adiponectin and elevated leptin levels may be involved in the pathogenesis of PE and associated with the development of severe disease.

Interactions Between Inflammatory and Oxidative Stress in Preeclampsia

Objective: Oxidative stress and a generalized inflammatory state are features of preeclampsia (PE). The objective of this study was to compare the levels of products of inflammatory reaction and oxidative stress markers in patients with PE, and to determine the relationship between oxidative stress and inflammation in PE. Methods: Plasma concentrations of high-sensitive C-reactive protein (hs-CRP), interleukin (IL)-6, tumor necrosis factor-alpha (TNF-α), malondialdehyde (MDA), and 8-isoprostane were measured in 53 women with PE and 20 age- and BMI-matched normotensive women. Results: The plasma concentrations of hs-CRP, IL-6, TNF-α, and 8-isoprostane were significantly higher in women with PE than in those with normotensive pregnancies, and these parameters, except for 8-isoprostane, were markedly elevated in those with severe PE (SPE), rather than mild PE (MPE). Moreover, plasma levels of 8-isoprostane, not MDA, were significantly correlated with the plasma levels of hs-CRP, IL-6, and TNF-α in patients with PE. Conclusions: These findings suggest that oxidative stress and inflammatory reaction are closely associated with PE, and the interactions between them may participate in the pathogenesis of PE.

Termination of early pregnancy in the scarred uterus with mifepristone and misoprostol

Objective: To analyze the safety and possibility of terminating early pregnancy up to 49 days gestation after cesarean section with mifepristone and misoprostol. Methods: One‐hundred and ninety‐two early pregnant women were recruited, of which, 35 cases with uterine cicatrix and 157 cases were no‐uterine cicatrix as control group. All of them took 25 mg of mifepristone, b.i.d. for 3 days and 600 μg of misoprostol on the 4th day. Results: Of the 35 cases with uterine cicatrix, 33 achieved complete abortion after medical abortion. The complete abortion rate was 94.29% (95% CI 81–99%) in the cicatrix group and 89.81% (95% CI 75–91%) in the control group. There were no obvious complications detected in the cicatrix group. Conclusion: For the termination of early pregnancy in scarred uterus, administration of mifepristone and misoprostol is safe and effective, and a further large series study needs be done to confirm its acceptability as a routine medication in such situations.

Expression of endothelial nitric oxide synthase traffic inducer in the placentas of women with pre-eclampsia

To investigate the expression of endothelial nitric oxide synthase traffic inducer (NOSTRIN) in the placenta of women with pre‐eclampsia (PE) and discuss its role in the pathogenesis of PE.

Role of hemeoxygenase-2 in pregnancy-induced hypertension

We conducted this study to observe the level of hemeoxygenase-2 (HO-2) expression in placentas of 56 term pregnant women, 42 with a diagnosis of pregnancy-induced hypertension (PIH) and 14 normal pregnancies by using immunohistochemistry and a high resolution pathological image analysis system (HPIAS-1000). ANOVA and the post-hoc test (Tukey) were used for statistical analysis. PF0.05 was considered significant. HO-2 is one of the isoenzyme of hemeoxygenase which catalyses the oxidation of heme in the presence of NADPH and cytochrome P-450 to produce carbon monoxide (CO) and bilirubin w1x. They are considered to promote vasodilation and protection of endothelium and other cells from oxidative injury, respectively w2,3x. In this study we found that the expression of HO-2 in normal pregnancy revealed a dark brownish-yellow color in the syncytiotrophoblast (STB) and villous endothelial cells (Fig. 1). However, interrupted light brownish color was noted in these cells of moderate and severe PIH women (Fig. 2). The level of HO-2 expression in STB and endothelial cells of moderate and severe PIH placentas were reduced compared with normal pregnancy

Fetal origin of single nucleated erythroblasts and free DNA in the peripheral blood of pregnant women

Objectives: To investigate the feasibility of using single fetal nucleated erythroblasts (FNRBCs) and free DNA in maternal blood for non‐invasive prenatal diagnosis. Methods: Single FNRBCs were isolated from 51 of 116 samples of maternal blood analyzed by micromanipulation after density gradient centrifugation. Furthermore, the nested polymerase chain reaction (PCR) method was used to amplify the SRY gene of single FNRBCs. Primer extension pre‐amplification and nested PCR were used to amplify the SRY gene of the plasma DNA extracted from 65 samples of maternal blood. Results: The detection rate of single FNRBCs was 90.20% (46/51). The concordance rates between real fetal sex and sex determined by amplification of the SRY gene from single cells and from free DNA analysis were 82.61% (38/46) and 90.77% (59/65), respectively. Conclusions: Single nucleated erythroblasts and free DNA in maternal blood are of fetal origin and can be valuable fetal material sources for non‐invasive prenatal diagnosis.

Neurokinin B and urotensin II levels in pre-eclampsia

Objective. To verify neurokinin B (NKB) and urotensin II (UII) plasma levels in pre-eclampsia (PE) and to determine the relationship between plasma NKB and UII levels. Method. A total of 60 women in the third trimester of pregnancy were recruited, 40 women with PE (study patients) and 20 age- and BMI-matched normotensive women (healthy controls). They were divided into three groups: the 20 normotensive pregnant women (Group 1); 20 women with mild PE (Group 2); 20 women with severe PE (Group 3). The plasma levels of NKB and UII were measured simultaneously by enzyme-linked immunosorbent assay. Results. Compared with controls, levels of NKB were significantly higher in women with mild or severe PE (p < 0.01 for both groups), levels of UII were significantly higher in women with mild or severe PE (p < 0.01 for both groups). Moreover, there was a positive correlation between plasma levels of NKB and UII in pre-eclamptic women (r = 0.783, p < 0.01). Conclusions. These findings suggest that there was an elevation of NKB and UII in the plasma of pre-eclamptic women. NKB and UII may be involved in the pathophysiology of PE and associated with the development of severe disease.

Placental and umbilical cord levels of neurokinin B and neurokinin B receptor in pre-eclampsia.

Neurokinin B (NKB) is traditionally classified as a neurotransmitter that is found in discrete neurons and immune cells [1]. Recently, it was found that the placenta—a tissue devoid of nerves—expresses the gene encoding NKB [2]. Page et al. [2] proposed that excessive secretion of NKB by the placenta could induce pre-eclampsia. We assessed the level of NKB andNKB receptor (NKR) expression in the placentas and umbilical cords of 60 primigravid women who delivered at term. Forty of the women were diagnosed with preeclampsia—according to the criteria of the International Society for the Study of Hypertension in Pregnancy [3]—and were classified as having mild (n=20) or severe (n=20) pre-eclampsia; 20 healthy pregnant women were included as controls. Specimens of placenta, umbilical artery, and umbilical vein were collected from each woman, and the blood vessels were flushed 3 times with cold phosphate-buffered saline lavage fluid to remove the blood components. Sections (4 μm) of the 3 specimens were cut from the paraffin block and immunostained separately with 50 μL of rabbit anti-human monoclonal anti-NKB antibody (Bs-0070R, Biosynthesis, China [1:150]) and 50 μL of rabbit anti-human monoclonal anti-NKR antibody (Bs-0166R, Biosynthesis, China [1:150]) for 2 hours at 28 °C, followed by incubation with biotinylated goat anti-rabbit immunoglobulin G (LHK612, Jingmei, China) for 30 minutes. For the negative control, the primary antibody was omitted. Sections were then incubated in diaminobenzidine reagent (LHK612, Jingmei, China) and counterstained with hematoxylin. Under a 400× light microscope, 3 visual fields were selected at random from every section, and the optical density valuewas assessed

Correlation of Cyr61 and CTGF in placentas from the late pre-eclamptic pregnancy.

Abstract It is thought that a shallow invasion of the maternal decidua by extravillous trophoblasts (EVT) is associated with the development of pre-eclampsia. Here, we focus on the expression of the proangiogenic proteins Cyr61 and CTGF in the human placenta during normal pregnancy compared with that in the late pre-eclamptic placenta. Cyr61 and CTGF are expressed in the extravillous trophoblast and in endothelial cells. We found the expression of Cyr61 was significantly decreased in pre-eclamptic placentas compared with matched controls. In contrast, the CTGF expression level was upregulated in pre-eclamptic placentas. There was a negative correlation between Cyr61 and CTGF. These results suggest that decreased Cyr61 and overexpressed CTGF may play a part in the development of pre-eclampsia.

Decreased Cyr61 under hypoxia induces extravillous trophoblasts apoptosis and preeclampsia

During placental development, oxygen environment is not only critical for trophoblasts migration and invasion, but also fundamental for appropriate placental perfusion. Cysteine-rich 61 (Cyr61, CCN1) was expressed in the extravillous trophoblasts (EVTs) and decreased in preeclampsia. Its regulatory properties in human first-trimester extravillous trophoblast cell line (TEV-1 cells) upon a low oxygen tension were investigated. The present study examined functional changes involved in adaptation to hypoxia of the TEV-1 cells, using cobalt chloride (CoCl2) as hypoxic mimic. It was found that hypoxia inhibited growth of TEV-1 cells and induced the increase of cell apoptosis (P<0.05). The Cyr61 expression in human EVTs was transcriptionally induced by CoCl2. Inappropriate EVTs apoptosis has been implicated in the failure of trophoblasts to fully invade and modify the uterine environment and Cyr61 down-regulation, potentially leading to preeclampsia.SummaryDuring placental development, oxygen environment is not only critical for trophoblasts migration and invasion, but also fundamental for appropriate placental perfusion. Cysteine-rich 61 (Cyr61, CCN1) was expressed in the extravillous trophoblasts (EVTs) and decreased in preeclampsia. Its regulatory properties in human first-trimester extravillous trophoblast cell line (TEV-1 cells) upon a low oxygen tension were investigated. The present study examined functional changes involved in adaptation to hypoxia of the TEV-1 cells, using cobalt chloride (CoCl2) as hypoxic mimic. It was found that hypoxia inhibited growth of TEV-1 cells and induced the increase of cell apoptosis (P<0.05). The Cyr61 expression in human EVTs was transcriptionally induced by CoCl2. Inappropriate EVTs apoptosis has been implicated in the failure of trophoblasts to fully invade and modify the uterine environment and Cyr61 down-regulation, potentially leading to preeclampsia.