Cytoplasm Of Syncytiotrophoblast Cells Research Articles

Fetal growth at term and placental oxidative stress in a tissue micro-array model: a histological and immunohistochemistry study.

This study examines 8-hydroxyguanine (8-oxo-Gua) staining in placental tissue samples based on fetal size at birth as well as its relationships with placental histology and other pregnancy variables. This prospective cohort study included women > 18 years with a singleton pregnancy, a live fetus, fluency in Italian, and delivery at term. A total of 165 pregnancies were included in the study. The nuclear syncytiotrophoblast 8-oxo-Gua staining score in LGA was substantially greater than in late FGR (p < 0.05), although the cytoplasm score was lower in SGA and LGA than in AGA (p < 0.05). Furthermore, a sex-specific pattern of 8-oxo-Gua staining was discovered in single-term placentas, with more oxidative damage found in the nuclei of syncytiotrophoblast cells and stromal and endothelial cells in AGA males compared to AGA females (p < 0.05). Second, the histological pattern of late FGR placentae differed by gender. Finally, a significant correlation (p < 0.05) was found between high-intensity 8-oxo-Gua staining in the cytoplasm of syncytiotrophoblast cells and thrombi in the chorionic plate or villi in males. On the other hand, female fetuses demonstrated a significant connection (p < 0.05) between high-intensity 8-oxo-Gua staining in endothelial and stromal cells and high birthweight MoM values. Our findings indicated a significant variation in the oxidative stress pattern between male and female placentae, implying that fetal growth is regulated differently in the two sexes.

Preeclampsia serum induces human glomerular vascular endothelial cell hyperpermeability via the HMGB1-Caveolin-1 pathway

To explore new ideas about the pathogeny of preeclampsia (PE) proteinuria, this study focused on whether severe PE serum (PES) could induce high-molecular-weight protein (HMWP) hyperpermeability in glomerular endothelial cells (GEC) via the HMGB1-Caveolin-1 (CAV-1) pathway. Normal pregnancy serum (NPS) and severe PES were used to treat primary human GEC monolayer for 24 h. The CAV-1 inhibitor methyl-beta-cyclodextrin (MBCD), the HMGB1 inhibitor glycyrrhizicacid (GA), recombinant HMGB1 (rHMGB1) were also used to treat GEC monolayer that were stimulated by NPS or severe PES. The dynamic permeability of GEC to HMWP was detected by Evans blue-labeled BSA and CAV-1 expression in GEC was analyzed by immunofluorescence staining and Western blotting. We detected HMGB1 expression in placenta and serum in normal pregnancy and severe PE. The results showed that severe PES significantly promoted GEC hyperpermeability and CAV-1 expression. By inhibiting CAV-1 expression, MBCD reversed severe PES-induced GEC monolayer permeability. HMGB1 expression in PE placenta and serum was significantly increased. Compared with that in normal placenta, HMGB1expression was increased in the cytoplasm of syncytiotrophoblast cells in PE placenta. GA decreased the severe PES-induced hyperpermeability and CAV-1 expression in GEC. rHMGB1 induced high expression levels of CAV-1 and HMWP hyperpermeability in GEC. In conclusion, HMGB1 is increased in severe PE patients and induces the expression of CAV-1 in GEC. High expression of CAV-1 in GEC can promote HMWP hyperpermeability, which may contribute to the development of PE proteinuria.

Expression of nuclear factor of activated T cells 5 and monocyte chemoattractant protein-1 and their relationship with macrophage infiltration in placenta of severe preeclampsia

Objective To explore the relationship between expression of nuclear factor of activated T cells 5 (NFAT5), monocyte chemoattractant protein-1(MCP-1) and CD68 marked macrophages in placental tissues of severe preeclampsia (sPE) . Methods Placental samples were collected from 30 normal ful-term healthy singleton pregnant women (control group), 31 singleton pregnant women with early-onset sPE(EPE) and 30 patients with late-onset sPE(LPE) who underwent elective cesarean section in the Third Affiliated Hospital of Zhengzhou University between January 2015 and January 2016. Immunohistochemistry was used to detect the expression and distribution of NFAT5 and MCP-1 in placental tissues and CD68 marked macrophage in decidual tissues. Real time-polymerase chain reaction technique was applied to analyze the expression of NFAT5 mRNA and MCP-1 mRNA in placental tissues. The correlations between placental NFAT5 mRNA and MCP-1 mRNA levels and CD68 marked macrophage were analyzed. One-way ANOVA, t-test, Chi-square test and Pearson's correlation analysis were used for statistics. Results (1) In all of the three groups, NFAT5 protein was expressed in nucleus and cytoplasm of syncytiotrophoblast cells, but less expressed in villi vascular endothelial cells; MCP-1 protein was expressed in cytoplasm of both syncytiotrophoblast cells and villi vascular endothelial cells. Positive NFAT5 expression rate in the EPE group was higher than in the LPE group [94%(29/31) vs 70%(21/30), χ2=5.720, P=0.017] and the control group [53%(16/30), χ2=12.743, P=0.001], respectively, the same results were abtained for MCP-1 expression [90%(28/31) vs 70%(21/30) and 43%(13/30), χ2=3.985 and 15.276, P=0.046 and 0.001]. (2) The NFAT5 mRNA level was higher in the EPE group than in the LPE and control group (1.07±0.03 vs 0.92±0.02 and 0.90±0.04, both P=0.001), respectively, and so was the MCP-1 mRNA level (1.08±0.12 vs 1.02±0.08 and 0.99±0.02, both P=0.001), respectively. (3) The number of macrophage in the EPE group was higher than that in the LPE group [(26.18±1.17) vs (9.78±0.31), t=75.358, P<0.001], and that in the LPE group was higher than that in the control group (9.78 ±0.31 vs 9.47±0.61, t=2.481, P<0.05). (4) In the EPE group, the expression of NFAT5 mRNA was positively correlated with the expression of both MCP-1 mRNA (r=0.554, P=0.001) and macrophage count (r=0.527, P=0.003). However, the level of MCP-1 mRNA was positively correlated with macrophage count only (r=0.395, P=0.031). Conclusions The increased expression of NFAT5 and MCP-1 in the placenta of patients with sPE, especially in the EPE, implies that NFAT5 and MCP-1 may contribute to the pathogenesis of EPE. Key words: Pre-eclampsia; NFATC transcription factors; Chemokine CCL2; Macrophages

Placental expression of lipoprotein lipase and endothelial lipase in women with severe preeclampsia

Objective To investigate the effect of abnormal lipid metabolism in the pathogenesis of preeclampsia.Methods Thirty women with severe preeclampsia who delivered by cesarean section in the International Peace Maternity & Child Health Hospital from November 1,2011 to June 30,2012,were included as the study group.Thirty normal pregnant women delivered during the same period by cesarean section were included as the control group.The mRNA levels of lipoprotein lipase (LPL) and endothelial lipase (EL) in the placentas were quantified by real-time polymerase chain reaction.The expression of LPL/EL protein was detected by Western-blot assay and the distribution on the placenta was determined by immunohistochemical staining.The maternal serum level of lipid markers was detected by automatic biochemical analyzer.Difference between the two groups was compared with t-test or rank-sum test.Results (1) The triglyceride (TG) concentration [(3.35±0.80) mmol/L vs (2.75± 0.92) mmol/L,t =3.082,P=0.003] and atherosclerosis index (AI) (2.76±0.46 vs 2.47±0.34,t=3.066,P=0.003) increased in the study group compared with the control group,while the concentration of high-density lipoprotein-cholestrol (HDL-c) decreased[(1.64 ± 0.34) mmol/L vs (1.85 ± 0.22) mmol/L,t=-3.157,P =0.003].(2) The median level of LPL mRNA expression in placenta of the study group was higher than that of the control [1.26 (0.46-1.58) vs 0.52 (0.34-0.84),Z=-2.587,P=0.010],whereas the expression of EL mRNA was lower [0.65 (0.48-0.76) vs 1.32 (0.94-1.62),Z=-4.154,P=0.000].(3) Immunohistochemical analysis showed that the placenta EL and LPL located in cytoplasm of syncytiotrophoblast cells at the materno-placental interface and of endothelial cells at the feto-placental interface.(4) Compared with the control group,the median level of LPL protein expression in placenta inthe study group increased [0.68(0.46-0.83) vs 0.31(0.15-0.55),Z=3.335,P=0.001],and the expression of EL protein decreased [0.13 (0.11 0.16) vs 0.70(0.56 0.81),Z=-5.711,P=0.000].The expression of LPL protein was negatively correlated with that of EL protein (r=-0.501,P=0.000).Conclusions Abnormal lipid metabolism contributes to the pathogenesis of severe preeclampsia. Key words: Pre-eclampsia; Lipoprotein lipase; Endothelial lipase; Placenta

Mixed germ cell testicular tumor presenting as metastatic cutaneous choriocarcinoma

To the Editor: A 38-year-old man, with polysubstance abuse and hepatitis C infection, was admitted to the hospital with nausea and coffee-ground emesis. He reported a 2-week history of two anterior chest nodules. Cutaneous examination revealed a 2.1- × 1.7-cm firm, pink nodule with punctate hemorrhagic crust and overlying pseudovesiculation on his right upper lateral chest wall. Adjacent to this nodule was a 0.5- × 0.5-cm papule with similar features (Fig 1). Additionally, he was found to have a unilateral enlarged, firm testicular mass with greatest dimension of 4.2 cm. The remainder of his physical examination was unremarkable. Laboratory tests showed a hemoglobin level of 4.9 g/dL. The patient had a normal basic metabolic panel, white blood cell and platelet count, as well as liver and coagulation function tests. The β-human chorionic gonadotropin (β-hCG) was remarkably elevated at 55,540.0 mIU/mL. The erythrocyte sedimentation rate was 44 mm/h. Values for antinuclear antibodies, carcinoembryonic antigen, CA19-9, α-fetoprotein, prostate-specific antigen, and haptoglobin were all normal. His hepatitis C virus quantitative viral load was 143,577 IU/mL. Metastatic workup revealed retroperitoneal lymphadenopathy, numerous bilateral lung masses, and a duodenal mass. Brain magnetic resonance imaging showed multiple enhancing hemorrhagic masses. The cells were negative for placental alkaline phosphatase, a marker for seminoma. Testicular orchiectomy revealed mixed germ cell tumor, with more than 95% of choriocarcinoma and less than 5% seminoma. Biopsy of the chest nodule revealed cutaneous metastasis of choriocarcinoma. Within the dermis was a dense, nodular, and interstitial infiltrate of poorly differentiated atypical and hyperchromatic cytotrophoblasts, admixed with several multinucleated hyperchromatic and atypical syncytiotrophoblasts (Fig 2, A and B). The β-hCG was diffusely positive in the cytoplasm of syncytiotrophoblastic cells and placental alkaline phosphatase was negative, thus confirming the diagnosis (Fig 2, C). In a mixed germ cell tumor, any admixture of a pure germ cell tumor, such as choriocarcinoma, can exist. Choriocarcinoma can rarely be found in its pure form; however, it is most commonly seen as a component of a mixed germ cell tumor. In both forms, choriocarcinoma has a biphasic pattern consisting of mononucleated cytotrophoblast cells that lie in sheets to form villus-like structures and a plexiform arrangement of syncytiotrophoblast cells that secrete β-hCG.1Ulbright T.M. The most common, clinically significant misdiagnoses in testicular tumor pathology, and how to avoid them.Adv Anat Pathol. 2008; 15: 18-27Crossref PubMed Scopus (52) Google Scholar Choriocarcinoma has a marked tendency to metastasize early. Skin metastasis is rare with only 12 cases previously reported and generally correlates with a poor prognosis.2Chen X. Xu L. Chen X. Teng X. Zheng S. Testicular choriocarcinoma metastatic to skin and multiple organs. Two case reports and review of literature.J Cutan Pathol. 2009; 37: 486-490Crossref Scopus (13) Google Scholar Cosnow and Fretzin3Cosnow I. Fretzin D.F. Choriocarcinoma metastatic to skin.Arch Dermatol. 1974; 109: 551-553Crossref PubMed Scopus (26) Google Scholar reported the first case in 1974, and a patient with these findings died 10 days after the initiation of chemotherapy.4Cheng D.C. Jennings T.A. Slominski A. Mihm Jr., C.M. Choriocarcinoma presenting as a cutaneous metastasis.J Cutan Pathol. 1995; 22: 374-377Crossref PubMed Scopus (30) Google Scholar A third case described a patient who died 3 months after the appearance of his cutaneous metastatic lesion to the upper back.5Satoko S. Yoshihiro N. Hiroshi H. Metastatic testicular choriocarcinoma of the skin: report and review of the literature.Am J Dermatopathol. 1996; 18: 633-636Crossref PubMed Scopus (37) Google Scholar First-line treatment of testicular choriocarcinoma is chemotherapy. Our patient was treated with right radical orchiectomy and chemotherapy. He received whole-brain radiation therapy and two cycles of chemotherapy with etoposide and cisplatin. The patient is currently alive 6 months after his presentation. Mixed germ cell tumors usually present with testicular enlargement, pain, or distant metastases. Cutaneous metastases are usually violaceous to red, hemorrhagic, infiltrative subcutaneous nodules located on the trunk, back, head, and scalp.5Satoko S. Yoshihiro N. Hiroshi H. Metastatic testicular choriocarcinoma of the skin: report and review of the literature.Am J Dermatopathol. 1996; 18: 633-636Crossref PubMed Scopus (37) Google Scholar In young men, metastatic testicular choriocarcinoma should be included in the differential diagnosis of papules or nodules in these locations.

Distribution of Notch family proteins in intrauterine growth restriction and hypertension complicated human term placentas

Members of the Notch family have been detected in many developmental and cell specification processes during placental development. However, Notch protein expression in Intrauterine Growth Restriction (IUGR) and Pregnancy Induced Hypertension (PIH) is not clear. In this study we aimed to clarify the immunolocalization of Notch proteins in full-term placentas after IUGR and PIH in comparison with normal placentas. Formalin-fixed, paraffin-embedded term placentas obtained by caesarean operations were processed for immunohistochemical localization of Notch 1, 2, 4 and Jagged 2. Transmission electron microscopy was also performed. In normal term placentas, all Notch proteins were intensely immunostained in the brush border of cells of the syncytiotrophoblast layer of the basal (maternal) side and the chorionic plate (fetal) side. The endothelial cells were also intensely immunostained in both sides for Notch 1. However, in IUGR and PIH placentas, the immunoreactivities of all Notch proteins were decreased significantly in the brush border of cells of the syncytiotrophoblast layer and the reaction was generally observed in the cytoplasm of syncytiotrophoblast cells in the basal and chorionic plate sides. The reactivity in endothelial cells was also significantly decreased. Our results have shown that the immunoreactivity and localization of Notch proteins is altered in pathologic placentas. Therefore, we propose that deregulated expression of Notch proteins may contribute to the disruption of trophoblast differentiation, endothelial cell function and/or feto-maternal traffic down-regulation during pregnancy or vice versa in such pathologic conditions.

Differential Distribution of Placental Leucine Aminopeptidase/Oxytocinase and Aminopeptidase A in Human Trophoblasts of Normal Placenta and Complete Hydatidiform Mole

Placental leucine aminopeptidase (P-LAP)/oxytocinase (OTase) degrades several small peptides such as oxytocin (OT), arginine vasopressin (AVP) and angiotensin III (ANGIII), and aminopeptidase A (AP-A) converts angiotensin II (ANGII) to ANGIII. These proteases play an important role in foetal growth and the maintenance of human homeostasis during pregnancy. In this study, we confirmed the distribution of P-LAP and AP-A proteins and messenger RNAs in human trophoblasts in normal placenta and complete hydatidiform mole by immunohistochemical and in-situ hybridization techniques. Immunoreactivity of P-LAP was mainly noted in the apical membrane of syncytiotrophoblasts, and the expression of messenger RNA (mRNA) for P-LAP was predominantly noted in the cytoplasm of syncytiotrophoblastic cells. However, immunoreactivity of AP-A was mainly noted in the apical membrane of cytotrophoblasts and in the basal zone of the syncytiotrophoblasts, and the expression of mRNA for AP-A was predominantly noted in cytoplasm of cytotrophoblastic cells and a little in cytoplasm of syncytiotrophoblastic cells. Thereby, the two proteases were differentially distributed both in normal placenta and hydatidiform mole throughout the gestational age. These results are useful for the further understanding of not only the pathophysiology of pregnancy, but also the pathogenesis of trophoblastic diseases.

Alkaline phosphatase histochemistry and biochemistry in the diagnosis of complete hydatidiform mole

The purpose of this study was a complementary method to the diagnosis and prognosis of complete hydatidiform mole (CHM) and differentiate it from the other cases of gestational trophoblatic diseases. This was done by examining the quality and quantity of the total and the placental alkaline phosphatase activity. The ALP in the tissues and sera from 12 patients were compared with 13 control normal non-pregnant and 30 control pregnant females. The enzyme activities were determined by biochemical and histochemical examination. The placental tissues were obtained from uterine curettage, or after delivery which then were frozen in a liquid nitrogen and processed for biochemical study. Cryosections were histochemically stained for ALP and PLAP by the azo coupling method. Isoenzyme specificity was evaluated by heating the tissue at 65 degrees C for 15 min while the including L-phenylalanine (50 mM), D-phenylalanine (50 mM) and L-homoarginine (50 mM) were used for chemical inhibition study. The activity of ALP and PLAP of patients were reduced in comparison with pregnant control group (P<0.05). There was no significant difference between the patients and non-pregnant control (P<0.05) group. The localization of enzyme activities in cryosections of all groups were in the basal, apical, and the cytoplasm of syncytiotrophoblast cells. The ALP in all the groups was thermostable (65 degrees C for 15 min) and was inhibited by L-phenylalanine, but no inhibition was seen with L homoarginine in patients group only. These findings suggest that the PLAP is a useful marker in the diagnosis and prognosis of hydatidiform mole.

Synthesis of leptin in human placenta.

Gender-based differences in serum leptin levels have been reported in umbilical cord blood, and leptin has been detectedin human amniotic fluid. In order to understand if leptin may be directly synthesized by human placentae an analysis made up of several steps was performed. First at all RT-PCR analysis from placenta-derived RNA was used to detect human leptin mRNA. The leptin-like immunoradioactivity detected in placentae extracts was identical to human leptin according to the criteria of charge, immunorecognition, SDS-PAGE analysis and blotting, indicating that intact leptin was found and no variants in size, charge or immunoactivity were present in the placentae. Finally an immunohistochemical analysis showed the presence of leptin in the cytoplasm of syncytiotrophoblast cells but not in the core of villi. leptin is synthesized as a single molecular variant identical to human recombinant leptin in human placentae at delivery.

Immunohistochemical Localisation of Transforming Growth Factor-&amp;beta; in First and Third Trimester Human Placenta

Recently it has been demonstrated that human placental tissue is a source of transforming growth factor-beta (TGF-beta) and that it expresses high TGF-beta mRNA activity. For a better understanding of its in vivo function, it was necessary to determine the site of TGF-beta synthesis in placenta. We have demonstrated that TGF-beta immunoreactivity is present in the cytoplasm of syncytiotrophoblast cells in both early and term placenta. The most intense staining was, however, observed in the first trimester trophoblast syncytial sprouts known to be an early stage in the development of placental villi. These results suggest the involvement of TGF-beta in the paracrine regulation of trophoblast-endometrial interaction.

Choriocarcinoma of the Testis Metastatic to the Skin

A case of choriocarcinoma of the testis metastatic to the skin is reported. In this case report the primary tumor was first diagnosed by the histopathologic findings in the cutaneous biopsy of a single nodule that appeared on the chest, with both syncytiotrophoblastic and cytotrophoblastic cells in the metastatic solid tumor islands. Using peroxidase-antiperoxidase techniques, beta-human chorionic gonadotropin (beta-HCG) was positive within the cytoplasm of syncytiotrophoblastic cells. The patient was treated with orchiectomy, chemotherapy, and radiotherapy. With these measures there was a decrease of chorionic gonadotropin serum levels to normal limits and 2 years after this treatment there is no evidence of recurrence.