CXCL12/CXCR4 Expression in Trophoblasts Takes Part in Materno-fetal Immune Tolerance and Vascular Remodeling

Summary： In this study, we investigated the expression of CXCL12 （SDF-1）/CXCR4 in trophoblasts and the role they play in the gestation. Immunochemistry was used to detect the expression of CXCR4 and CXCLI 2 in human villi and placenta. Highly purified extra-viUous trophoblasts （EVTs） ere detected for CXCR4 and CXCL12 in vitro by immunocytochemistry. The chemotaxis of CXCL12 was tested in transweU and the chemotactic activity was quantitatively examined. It was suggested that both CXCR4 and CXCL12 were expressed in trophoblasts and were decreased with the gestation time P〈0.05）. In a certain coverage, CXCL12 exhibited chemotactic activity which was positively correlated with its concentration [（r）=0.68, P〈0.01], the maximum chemotactic index （CI） was 1.62±0.12. Our results suggest that interaction between CXCR4 and CXCL12 is involved in materno-fetal immunological tolerance in all three trimesters of gestation and contributes to the invasion of EVTs during pregnancy.

Increased Apoptosis in Chorionic Trophoblasts of Human Fetal Membranes with Labor at Term

Objective: To determine the association of apoptosis in the layers of human fetal membranes distal to rupture site with labor at term. Study Design: Fetal membranes were collected from elective cesarean sections (n = 8) and spontaneous vaginal deliveries (n = 8) at term. The extent of apoptosis within fetal membrane layers was determined using terminal deoxynucleotidyl transferase deoxy-UTP-nick end labeling (TUNEL) assay and western blots for pro-apoptotic active caspase-3 and anti-apoptotic Bcl-2. Results: Apoptotic index in chorionic trophoblasts of membranes distal to rupture site obtained after vaginal delivery was 3-fold higher than those obtained from elective cesarean (11.57% ± 4.98% and 4.05% ± 2.4% respectively;p = 0.012). The choriodecidua layers after vaginal deliveries had higher expression of the pro-apoptotic active caspase-3 and less expression of the anti-apoptotic Bcl-2 than those obtained from elective cesarean sections. Conclusions: Labor at term is associated with increased apoptosis in chorionic trophoblast cells of human fetal membranes distal to rupture site.

Impact of Silencing MMP9 Gene on the Biological Behaviors of Trophoblasts

This study examined the effect of MMP9 gene on the biological behaviors of trophoblasts and explore the relation between MMP9 gene and the ＂superficial implantation of placenta＂. In vitro cultured trophoblasts （TEV-1 cells） were transfected with synthesized double-stranded MMP9 RNA （siRNA） by using lipofectamine2000TM technique and the expressions of MMP9 mRNA and protein and the growth and invasiveness of the TEV-1 cells were determined. Our results showed that siRNA transfection could significantly inhibit the expression of MMP9 gene in the TEV-1 cells and the growth and invasiveness of the TEV-1 cells transfected RNA was significantly reduced （P0.01）. We are led to conclude that silencing of MMP9 gene with siRNA can inhibit the growth and invasiveness of trophoblasts and increasing the expression of MMP9 might help prevent and treat preeclampsia.

Effect of Different Concentrations of Neogenin on Proliferation,Apoptosis and Related Proliferative Factors in Human Trophoblasts

The underlying effect of different concentrations of neogenin on proliferation, apoptosis and the related proliferative factors in human trophoblasts was explored in order to understand the function of neogenin during placentation. TEV-1 cell line was cultured and the expression of netrin-1 was detected by using indirect cellular immunofluorescence. Exponentially growing TEV-1 cells were treated by different concentrations of neogenin (0, 1, 5, 10, 50 ng/mL) for 24 h. Cell viability was measured by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. TEV-1 cell apoptosis was assessed by flow cytometry (FCM). The expression of netrin-1 mRNA and protein in TEV-1 cells was examined by using real-time PCR and Western blot, respectively. It was found that immunoreactivity for netrin-1 was observed in cytoplasm of the trophoblasts. Immediately after treatment with different concentrations of neogenin for 24 h, the netrin-1 expression began to increase. Real-time PCR revealed that the expression level of netrin-1 mRNA was 37.59±10.25 times higher than control group when TEV-1 cells were exposed to 50 ng/mL neogenin (P<0.01), and the same tendency was seen by using Western blot. MTT results showed that proliferation of TEV-1 cells was independent of neogenin. Meanwhile, apoptosis was significantly increased to (22.15±6.15)% at 50 ng/mL neogenin and (6.55±0.25)% without neogenin (P<0.01). It is suggested that neogenin regulates proliferation and apoptosis of TEV-1 cells. And it can enhance the ability of TEV-1 cells to express netrin-1 in a dose-dependent manner. Neogenin may play an important biological role in the normal human pregnancy and contribute to the physiological pregnancy process.

Upregulation of sFlt-1 by Trophoblasts Induces the Barrier Dysfunction of Glomerular Endothelial Cells

This study examined the effect of over-expression of sFlt-1 by trophoblasts on the barrier function of glomerular endothelial cells and the role of VEGF in this process in order to explore the pathogenesis of glomerular disease in preeclampsia. SFlt-1 expression in the human trophoblasts （TEV-1 cells） was enhanced by transfecting sFlt-1 plasmid DNA into TEV-1 cells. The monolayer barrier fimction of glomerular endothelial cells （ciGEnCs） was determined by measuring the fluorescence intensity of bovine serum albumin （BSA） that crossed the monolayer of glomerular endothelial cells. The results showed that the over-expression of sFlt-1 by TEV-1 cells led to the barrier dysfunction of ciGEnCs, and the exogenous VEGF could alleviate the ciGEnCs dysfunction resulting from the over-expression of sFlt- 1 to a certain extent. It was concluded that the dysregulation of sFlt- 1 and VEGF in preeclamptic pregnancy may contribute to the barrier dysfunction of glomerular endothelial cells, and VEGF may play an important role in maintaining the barrier function of glomerular endothelial cells, but it may not be the sole factor.

Focal adhesion kinase signaling is necessary for the hydrogen sulfide-enhanced proliferation,migration,and invasion of HTR8/SVneo human trophoblasts

Objective:Hydrogen sulfide(H_(2)S)has been elucidated that it promotes migration and invasion in human placenta trophoblasts.However,the signaling pathway underlying H_(2)S-based regulation of trophoblasts remains unknown.Hence,we investigated the potential effect of sodium hydrosulfide(NaHS),an exogenous H_(2)S donor,on extravillous trophoblasts.Methods:The Cell Counting Kit-8 was used to detect the proliferative activity of trophoblasts and to screen the optimal concentration of NaHS.The migration and invasion of HTR8/SVneo cells were measured by Transwell assays.Gene expression was determined by quantitative real-time PCR analysis.Protein expression was determined by western blot.Results:We found that NaHS could promote the proliferation,migration,and invasion of HTR8/SVneo cells.The phosphorylation of focal adhesion kinase(FAK),Src,and extracellular signal-regulated kinase(ERK)were activated by NaHS.Moreover,NaHS also upregulated the expression of matrix metalloproteinase-2(MMP-2)and MMP-9,downregulated the expression of E-cadherin in HTR8/SVneo cells.The application of NaHS could increase the expression of cystathionine-β-synthase.Conclusion:Both FAK-Src signaling and the upstream signaling cascade of ERK activation play a significant important role in NaHS-induced proliferation,migration,and invasion via upregulating activity of MMP-2,MMP-9,and downregulating E-cadherin in HTR8/SVneo cells.These novel findings may provide a strong foundation for the clinical application of H_(2)S donor drugs.

Upregulation of CD81 in trophoblasts induces an imbalance of Treg/Th17 cells by promoting IL-6 expression in preeclampsia

The disturbance of maternal immune tolerance to a semiallogeneic fetus is recognized as one of the key pathologies of preeclampsia(PE),in which an imbalance between the inflammation-limiting regulatory T cells(Tregs)and the inflammationmediating Th17 cells plays an essential role.Previously,we reported that the abnormal upregulation of tetraspannin CD81 in trophoblast cells(fetal component)participated in the pathogenesis of PE.However,as one of the potential immune regulatory molecules,whether CD81 induces PE by interfering with the balance of the maternal immune system has not yet been clarified.Thus,we investigated the relationship between the upregulation of CD81 in trophoblast cells and the imbalance of Treg and Th17 cells in mothers.Here,we demonstrated that upregulation of CD81 in trophoblast cells was accompanied by a decrease in Treg cells and an increase in Th17 cells in both the basal plate(placental maternal side)and peripheral blood of patients with PE.In vitro culture of naïve T cells with medium from the CD81-overexpressing trophoblast cell line HTR-8 resulted in enhanced differentiation of T cells into Th17 cells and decreased the formation of Tregs,which was dependent on the paracrine signaling of IL-6 in trophocytes,induced by CD81.In a CD81-induced PE rat model,we found a significant shift of T cell differentiation towards Th17 cells,and administration of IL-6 antibody mitigated the PE phenotype and the imbalance of the Treg/Th17 cells.These results define a vital regulatory cascade involving trophocyte-derived CD81,IL-6,and maternal Treg/Th17 cells in the pathogenesis of PE and suggests new therapeutic approaches based on CD81 and IL-6 downregulation to prevent human PE.

Uterine epithelioid trophoblastic tumor with the main manifestation of increased human chorionic gonadotropin:A case report

BACKGROUND Epithelioid trophoblastic tumor(ETT)is an extremely rare malignant gestational trophoblastic neoplasm commonly presenting with abnormal vaginal bleeding,abdominal pain,and increased human chorionic gonadotropin(hCG).This study reported a case of uterine ETT with the main manifestation being increased hCG.CASE SUMMARY A 39-year-old female was referred to the Ningbo Maternal and Child Hospital of China in December 2022,complaining of increased hCG levels for 1 month.Magnetic resonance imaging revealed gestational trophoblastic tumor,and hysteroscopic electrotomy and curettage of intrauterine hyperplasia were performed.The patient was diagnosed with uterine ETT through postoperative pathological examination and immunohistochemical results.Total laparoscopic hysterectomy and bilateral salpingectomy were performed,and hCG levels returned to normal.The patient was without recurrence during the postoperative 3-month follow-up.CONCLUSION This study reported a case of uterine ETT with the main manifestation being increased hCG,highlighting that ETT should be considered in the presence of abnormal hCG.A total laparoscopic hysterectomy is recommended.

Relationship between expression of hepatocyte grow factor and apoptosis of trophoblasts in hypertensive disorder complicating pregnancy

The aim of this study was to investigate the expression of hepatocyte growth factor(HGF)and Fas in placentas of uncomplicated pregnant women and those with hypertensive disorder complicating pregnancy(HDCP),and elucidate the possible relationship between HGF and apopto-sis of trophoblasts.Reverse transcription-polymerase chain reaction(RT-PCR)was undertaken to examine the concentra-tion of HGF mRNA and Fas mRNA obtained from 34 cases of HDCP and 30 cases of uncomplicated pregnancy.The expression of HGF mRNA in mild preeclampsia,severe preeclampsia and eclampsia cases was significantly lower than that in the uncomplicated cases(0.43P0.12,0.38P0.09,0.19P0.17 versus 0.67P0.19,P<0.05),while the expres-sion of Fas mRNAin mild preeclampsia,severe preeclampsia and eclampisa cases was significantly higher than that in the uncomplicated cases(1.58P0.26,2.96P0.14,5.98P1.17 versus 1.01P0.36,P<0.05).For HGF mRNA and Fas mRNA,there was no difference between gestational hyper-tension cases and control cases.Decreased HGF mRNA or increased Fas mRNA was found along with the progress of HDCP.Negative correlation was found between the expressions of HGF and Fas.These results indicate that HGF inhibits the apoptosis mediated by Fas,and the reduced expression of HGF in HDCP may be responsible for the apoptosis of trophoblasts.

A Defective CXCL16/CXCR6 Axis Increases the Risk of Pregnancy Loss via the Abnormal Crosstalk between Decidual γδ T Cells and Trophoblasts

Objective::The maternal-fetal interface undergoes dynamic changes to allow the fetus to grow and develop in the uterus.The interaction between decidualγδT cells and trophoblasts plays a pivotal role during successful pregnancy;however,their physiological functions in early-term human pregnancy are still not completely illustrated.This study was undertaken to illustrate the functional roles of CXCL16/CXCR6 to prevent pregnancy loss via the crosstalk between decidualγδT cells and HTR8/SVneo trophoblast cells.Methods::The percentile of CXCR6+γδT cells in the peripheral blood from normal female and recurrent spontaneous abortion(RSA)patients was analyzed by flow cytometry.The expression of CXCR6 was detected in decidual immune cells via flow cytometry,and the expression of CXCL16 was analyzed in HTR8/SVneo trophoblast cells and lentivirus(LV)-HTR8/SVneo trophoblast cells via enzyme-linked immunosorbent assay.Reverse transcriptase-polymerase chain reaction was used to verify the expression of the CXCL16 gene in LV-HTR8/SVneo trophoblast cells.Expression of granzyme B and cytokines and proliferation of decidualγδT cocultured with HTR8/SVneo trophoblast cells were analyzed by flow cytometry.Invasion of HTR8/SVneo trophoblast cells was assessed via Matrigel transwell assay.Adoptive transfer was induced in vivo further to illustrate that the normal expression of CXCL16/CXCR6 could prevent pregnancy loss.Results::The percentile of CXCR6+γδT cells in the peripheral blood from RSA patients was lower than normal pregnancies.The expression of CXCR6 was highest in the decidualγδT cells among decidual immune cells,and the expression of CXCL16 increased as the amount of HTR8/SVneo trophoblast cells increased.Expression of granzyme B in the decidualγδT cells was downregulated by cocultured with HTR8/SVneo cells dependent of CXCL16,and HTR8/SVneo trophoblast cells induced the Th2 cytokines production in the decidualγδT cells.Both the expression of CXCR6 in the decidualγδT cells and proliferation of the decidualγδT cells were promoted by HTR8/SVneo trophoblast cells.On the other hand,decidualγδT cells enhanced the invasion of HTR8/SVneo trophoblast cells and thus promoted embryo implantation.In vivo study was taken further and shown that low expression of CXCL16/CXCR6 results in pregnancy loss because of dialog disorder between decidualγδT cells and trophoblasts.Conclusions::Low expression of CXCL16/CXCR6 results in pregnancy loss because of the dialog disorder between decidualγδT cells and trophoblasts,and it showed a light on the effective strategy of adoptive transfer of CXCR6+γδT cells on the treatment of RSA.This observation provides a scientific basis on which a potential strategy can be applied to the early-detect and treatment of RSA.

Human HAND1 inhibits the conversion of cholesterol to steroids in trophoblasts

Steroidogenesis from cholesterol in placental trophoblasts is fundamentally involved in the establishment and maintenance of pregnancy.The transcription factor gene heart and neural crest derivatives expressed1(Hand1)promotes differentiation of mouse trophoblast giant cells.However,the role of HAND1 in human trophoblasts remains unknown.Here,we report that HAND1 inhibits human trophoblastic progesterone(P4)and estradiol(E2)from cholesterol through downregulation of the expression of steroidogenic enzymes,including aromatase,P450 cholesterol side-chain cleavage enzyme(P450 scc),and 3β-hydroxysteroid dehydrogenase type 1(3β-HSD1).Mechanically,although HAND1 inhibits transcription of aromatase by directly binding to aromatase gene promoter,it restrains transcription of P450 scc by upregulation of the methylation status of P450 scc gene promoter through its binding to ALKBH1,a demethylase.Unlike aromatase and P450 scc,HAND1 decreases 3β-HSD1 m RNA levels by the reduction of its RNA stability through binding to and subsequent destabilizing protein Hu R.Finally,HAND1 suppresses circulating P4 and E2 levels derived from JEG-3 xenograft and attenuates uterine response to P4 and E2.Thus,our results uncover a hitherto uncharacterized role of HAND1 in the regulation of cholesterol metabolism in human trophoblasts,which may help pinpoint the underlying mechanisms involved in supporting the development and physiological function of the human placenta.

Epithelioid trophoblastic tumor of the lower uterine segment and cervical canal:A case report

BACKGROUND Epithelioid trophoblastic tumor(ETT) is the rarest type of gestational trophoblastic tumor(GTT). It has been reported that more than 50% of ETTs arise in the uterine cervix or the lower uterine segment. Here, we report a case of ETT within the lower uterine segment and cervical canal and discuss its manifestations,possible causes, and related influencing factors.CASE SUMMARY A 35-year-old woman(gravida 7, miscarriage 3, induction 2 with 1 being twins,para 2 of cesarean section, live 2), who had amenorrhea for 9 mo after breastfeeding for 22 mo after the last cesarean section, was diagnosed with ETT. The lesion was present in the lower uterine segment and endocervical canal with severe involvement of the anterior wall of the lower uterine segment and the front wall of the lower uterine segment where the cesarean incisions were made.Laboratory tests showed slight elevation of serum beta-human chorionic gonadotropin. Intraoperative exploration showed the presence of a normal-sized uterus body with an enlarged tumor in the lower uterine segment. The surface of the lower uterine segment was light blue, the entire lesion was approximately about 8cm × 8 cm × 9 cm, with compression and displacement of the surrounding tissue.Histological examination diagnosed ETT. Immunohistochemical analysis showed positive expression of p63, with a Ki-67 proliferation index of 40%.CONCLUSION A search of the PubMed database using the search terms "cesarean section" and "epithelioid trophoblastic tumor" retrieved nine articles, including 13 cases of ETT and ETT-related lesions, all 13 cases had a history of cesarean section, and the lesions were all located at the cesarean section incision on the anterior wall of the lower uterine segment. The present case is the 14th reported case of ETT after cesarean section. Therefore, we deduced that cesarean section trauma had an important effect on the occurrence of ETT at this site.

UCK2 promotes the proliferation,migration,and invasion of trophoblast cells in preeclampsia by activating the STAT3 pathway

Background:Preeclampsia(PE),characterized by hypertension and proteinuria,leads to serious maternal and infant complications.Uridine-cytidine kinase 2(UCK2)belongs to the UCK family,a class of enzymes that catalyzes the conversion of uridine and cytidine to monophosphate form.However,the role of UCK2 in PE has not been reported.Methods:The expression of UCK2 was detected in the placenta of PE patients and N(ω)-nitro-L-arginine methyl esterinduced PE mouse model.Through forced up-regulation or down-regulation of UCK2 in vitro,we examined the effects of UCK2 on the proliferation,apoptosis,migration,and invasion of trophoblast cells.Stattic,the inhibitor of STAT3 pathway,was used to investigate whether the STAT3 pathway mediates the biological function of UCK2 in trophoblast cells.Results:The present study found that UCK2 showed low expression in the placenta of PE patients and PE mouse model.MTT(3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide)and flow cytometry assays verified that up-regulation of UCK2 promoted the proliferation of trophoblast cells,while the silence of UCK2 suppressed cell proliferation.Besides,flow cytometry and TdT-mediated dUTP Nick-End Labeling assays demonstrated that knockdown of UCK2 resulted in apoptosis of trophoblast cells.The wound healing and transwell assays showed that the migration and invasion activities of the trophoblast cells were facilitated by the overexpression of UCK2 and were blocked by the silence of UCK2.Furthermore,the expression of phosphorylated STAT3 was increased with the upregulation of UCK2 and decreased with the inhibition of UCK2.When the STAT3 pathway was blocked by its inhibitor stattic,the promotion effects of UCK2 on trophoblast cells were suppressed.Conclusion:UCK2 promotes the proliferation,migration,and invasion of trophoblast cells,and these effects may be partly mediated by the activation of the STAT3 pathway.

Primary ovarian choriocarcinoma occurring in a postmenopausal woman:A case report

BACKGROUND Nongestational ovarian choriocarcinoma(NGOC)is a rare but aggressive neoplasm with limited sensitivity to chemotherapy and a very poor prognosis.Few cases of NGOC have been reported,and there is limited information regarding its clinical features,treatment protocols,or prognosis.CASE SUMMARY A postmenopausal woman in her 5th decade of life visited our clinic because of abnormal vaginal bleeding and an abdominal mass.Although she had been menopausal for more than eight years and her last abortion occurred nine years ago,she had an increased level of serumβ-human chorionic gonadotropin(β-hCG).Thus,an ovarian neoplasm of trophoblastic origin was suspected,and exploratory laparotomy was performed.Based on the patient’s clinical history and the histopathological examination and immunohistochemistry results obtained postoperatively,we concluded that she most likely had primary NGOC.Cytoreductive surgery was performed in combination with adjuvant chemotherapy comprising bleomycin,etoposide,and cisplatin.Serumβ-hCG levels decreased to normal after two cycles,and there was no evidence of recurrence after four cycles of chemotherapy.CONCLUSION Even in postmenopausal women,ovarian choriocarcinoma should be considered in the initial differential diagnosis for an adnexal mass.

The expression of TUSC3 in Preeclampsia and the function in trophoblast cell

Objective:In this study,we aimed to explore the expression of TUSC3 in Preeclampsia and to research the potential function of TUSC3 in placental trophoblast cells.Methods:We collected 10 cases of normal placental tissues and preeclampsia placental tissues,respectively.These parturient received treatment at the First Affiliated Hospital of Hainan Medical University between June 1,2020,and December 31,2022.The expression of TUSC3 in placenta was detected by immunohistochemistry.The effect of TUSC3 on the migration and invasion of HTR8/SVneo cells was analyzed by migration assay and Transwell assay.Results:The expression of TUSC3 was slightly increased in placental villis in preeclampsia.Immunohistochemistry and qRT-PCR were used to detect the expression of TUSC3 protein and mRNA in placental tissues.TUSC3 was markedly upregulated in PE placental tissues(P<0.01).The results of migration assay and Transwell assay showed that the migration rate and the number of invasive cells were significantly decreased in HTR8 overexpressing TUSC3(P<0.01).Conclusions:TUSC3 was markedly increased in PE placental tissues and inhibited trophoblast cells migration and invasion.

Exosome-derived miR-146a-5p from decidual macrophages in preeclampsia inhibits the viability and invasive ability of trophoblast cells by targeting HIF1α

Objective:To investigate the effect of exosomes secreted by decidual macrophages on trophoblast cells and their molecular mechanism.Methods:The decidual tissues of patients with preeclampsia(PE)and normal-term pregnant women were collected.Macrophages were obtained by the density gradient method and then flow cell sorting,then the exosomes were extracted.The structure of the exosomes was observed by transmission electron microscope.The expression of CD63,a marker protein of the exocrine body,was detected by western blot,and the exosomes were identified.CCK-8 was used to detect the effect of exosomes on trophoblast cell viability.Transwell migration experiment was used to detect the influence on migration ability.The expression of miR-146a-5p in exosomes was detected by qPCR.The effect of exosomes on the expression of HIF1αprotein in trophoblasts was detected by western blot and detection of the binding site between miR-146a-5p and HIF1αby double luciferase reporter gene was conducted.Results:The exosomes of macrophages present a"cake"structure with a middle depression about 30-130 nm in diameter,and CD63 is highly expressed,which conforms to the characteristics of exosomes.Compared with the normal group,the exosomes of decidual macrophages in the PE group inhibited the activity and migration of trophoblast cells(P<0.001).The expression of miR-146a-5p in the exosomes of decidual macrophages in the PE decreased significantly,and after exosomes of PE decidual macrophages treating trophoblast cells,the protein expression of HIF1αin trophoblast cells was significantly increased.There are targeted binding sites between miR-146a-5p and HIF1α.Conclusion:PE decidual macrophage exosomes can inhibit the viability and migration of trophoblast cells,which may be related to the decreased expression of miR-146a-5p in exosomes,thus promoting HIF1αprotein expression of trophoblast cells.

Updates in the Diagnosis of Gestational Trophoblast Disease

GTD (Gestational Trophoblastic Disease) is a pathology that encompasses benign and malignant clinical forms, affects women of childbearing age, has a variable incidence and is more frequent in developing or underdeveloped countries, colliding with the economic barrier. The frequent absence of clear protocols and guidelines for the correct diagnosis of the pathology results in inadequate classification, imprecise treatment and failed post-therapeutic observation, increasing the risk of relapses, morbidity and mortality. The present study aims to point out updated national and international practice protocols of diagnosis of GTD, through an integrative review. Seven articles were selected and it was observed that the main international reference centers are agreed with the management suggested by the IFGO (International Federation of Gynecology and Obstetrics), being the conduct in the Hydatidiform Mole (HM): evacuation by suction and curettage under ultrasound guidance, followed by hCG monitoring every 1 - 2 weeks until normalized (usually one month for Partial Hydatidiform Mole six months for Complete Hydatidiform Mole and one year for Gestational Trophoblastic Neoplasia). Unfortunately, regarding the diagnosis of MH, the guidelines of some countries show the absence or difficulty of access to the karyotype test and ploid p57 or pelvic ultrasound accompanying the uterine curettage, contrary to what is proposed by the IFGO guideline. Establishing and complying with consistent guidelines can improve patient care, with early diagnosis of the pathology and its complications, reducing the rate of recurrence, morbidity and mortality, especially in less developed countries.

持续低水平hCG妊娠滋养细胞肿瘤1例

患者,女,29岁,孕5产2,因产后h CG持续低水平阳性5月余于2014年2月7日入院。患者曾人工流产2次后于2007年行剖宫产1次,2012年因部分性葡萄胎在我院治疗痊愈后出院,2013年再次足月剖宫产分娩一健康婴儿。因仍在葡萄胎随访期,遂于产后复查h CG,产后5月余复查血h CG波动在100~500 mI U/mL之间,因此收入院治疗。患者入院时一般状况可,无贫血貌,无咳嗽咳痰,无阴道流血等不适。

Bone morphogenetic protein-4 affects both trophoblast and non-trophoblast lineage-associated gene expression in human embryonic stem cells

Human embryonic stem cells (hESC) can be induced to differentiate to trophoblast by bone morphogenetic proteins (BMPs) and by aggregation to form embryoid bodies (EB), but there are many differences and controversies regarding the nature of the differentiated cells. Our goals herein were to determine if BG02 cells form trophoblast-like cells (a) in the presence of BMP4-plus-basic fibroblast growth factor (FGF-2) and (b) upon EB formation, and (c) whether the BMP4 antagonist noggin elicits direct effects on gene expression and hormone production in the cells. Transcriptome profiling of hESC incubated with BMP4/FGF-2 showed a down-regulation of pluripotency-associated genes, an up-regulation of trophoblast-associated genes, and either a down-regulation or no change in gene expression for many markers of the three embryonic germ layers. Yet, there was up-regulation of several genes associated with mesoderm, ectoderm, and endoderm, strongly suggesting that differentiation to trophoblast-like cells under the conditions used does not yield a homogeneous cell type. Several genes, heretofore unreported, were identified that are altered in hESC in response to BMP4-mediated differentiation. The production of human chorionic gonadotropin (hCG), progesterone, and estradiol in the differentiated cells confirmed that trophoblast-like cells were obtained. Gene expression by EB was characterized by an up-regulation of a number of genes associated with trophoblast, ectoderm, endoderm, and mesoderm, and the production of hCG and progesterone confirmed that trophoblast-like cells were formed. These results suggest that, in the presence of FGF-2, BG02 cells respond to BMP4 to yield trophoblast-like cells, which are also obtained upon EB formation. Thus, BMP4-mediated differentiation of hESC represents a viable cell system for studying early developmental events post-implantation;however, up-regulation of non-trophoblast genes suggests a somewhat diverse response to BMP4/FGF-2. Noggin altered the transcription of a limited number of genes but, not surprisingly, did not lead to secretion of hormones.

子宫上皮样滋养细胞肿瘤病例报道并文献复习

上皮样滋养细胞肿瘤（epithelioid trophoblastic tumour,ETT）是妊娠滋养细胞肿瘤（Gestational Trophoblastic neopla-sia,GTN）中很罕见的一种类型,具有特殊的组织和免疫形态表现,因其发病罕见,起病机制不清,组织形态与绒毛膜癌（choriocarcinoma,CC）、胎盘部位滋养细胞肿瘤（placental site trophoblastic tumor,PSTT）、宫颈鳞状细胞癌（cervical squamous cell carcinoma,SCC）有相似性,且对化疗不敏感,故临床诊治比较困难。为提高对该病的认识,本文结合文献复习对我院收治的1例ETT病例进行临床特征、组织学形态、免疫表现及治疗进行讨论。