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.

Effect of Leptin on Cytotrophoblast Proliferation and Invasion

The effects of leptin on cytotrophoblast proliferation and invasion activity were investigated. Immunohistochemistry was used to determine the placental expression of leptin in first-trimester pregnancy. By using RT-PCR and quantitative real-time PCR, the expression of leptin in cytotrophoblast and the effect of leptin on cytotrophoblast secretion were detected. The potential of cell proliferation, invasiveness and migration was assessed by MTT, Transwell invasion assay and migration assay respectively when the cytotrophoblast was cultured with different concentrations of leptin. The results showed that： （1） Leptin was distributed diffusely around cell membrane, in cytoplasma, and on nuclear mem- brane of cytotrophoblast; （2） Leptin mRNA was expressed in cytotrophoblast. Ten ng/mL leptin could promote the secretion of cytotrophoblast significantly （P〈0.01）; （3） After culture with different concentrations of leptin for 24 h or longer, the proliferation of cytotrophoblast was inhibited, while in 24 h leptin could promote cytotrophoblast invasion and migration. Leptin at a concentration of 500 ng/mL could promote cytotrophoblast invasiveness and migration significantly as compared with controls （P〈0.05）. It was suggested that leptin could inhibit cytotrophoblast proliferation, and promote cytotro- phoblast invasion and migration activity.

Special epithelioid trophoblastic tumor:A case report

BACKGROUND Epithelioid trophoblastic tumor(ETT)is a special type of gestational trophoblastic tumor.However,its pathogenesis has been incompletely elucidated.ETT rarely occurs in the ovaries and fallopian tubes,unlike placental site trophoblastic tumor,requiring a histopathological biopsy and immunohistochemistry for further diagnosis.CASE SUMMARY A 29-year-old woman with irregular vaginal bleeding and elevated serum chorionic gonadotropin(β-hCG)levels presented similar symptoms to ectopic pregnancy.Transvaginal ultrasound revealed abnormal echoes of the left adnexa.Postoperatively,the pathology of the left ovary and fallopian tube was reported as ETT.The patient was followed up with regular hCG measurements and ultrasounds.The blood hCG values showed an upward trend 3 mo after the operation and then chemotherapy was prescribed.The current health status is normal.CONCLUSION For women of childbearing age with elevated serumβ-hCG levels,practitioners should consider ETT and be alert to the poor prognosis of the disease.After surgery,the patient’s condition should be closely observed to prevent recurrence and metastasis.Postoperative chemotherapy is only helpful for treating the disease to a certain extent.

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.

Possible link between congenital uterine malformations and epitheliod trophoblastic tumor

Background: Epitheloid trophoblast tumor (ETT) is a tenuous type of gestational trophoblastic disease. Although clinically ETT behave in variable fashion, it is considered as a potentially malignant tumor, fatal malignancy occurs in 10% of the cases. Case and Conclusion: A 41 years old patient, who previously underwent Tompkins operation because of congenital uterine septum was admitted to our clinic due to irregular bleeding. Despite of serum hCG levels under the upper limit of normal, histopathology analysis of D&C obtained endometrial samples confirmed the presence of ETT by immunostainings. Henceforth we performed prompt abdominal hysterectomy and preserved the normal structured ovaries. According to the müllerianosis theory of endometriosis aberrant differentiation or migration could cause spreading of cells throughout the fetal organogenesis of the uterus. These cells in an apoptosis week environment might correlate with the initiation of ETT. As a conclusion we suggest further studies to assess the link between ectopic cells and ETT, to gain a better understanding in the pathomechanism of the tumor.

Gestational Trophoblastic Neoplasia: Clinical and Therapeutic Profile in Madagascar

Gestational trophoblastic disease (GTD) develops from abnormal cellular proliferation of trophoblasts following fertilization. This includes complete and partial hydatidiform mole (HM) and gestational trophoblastic neoplasia (GTN). The aim of this study was to report the epidemiological, clinical and therapeutic profile of gestational trophoblastic neoplasia (GTN) over period of ten years in the department of Oncology Radiotherapy at the University Hospital Joseph Ravoahangy Andrianavalona (HJRA) Antananarivo Madagascar. Medical records of women diagnosed with GTD in the department of Oncology Radiotherapy at HJRA from January 1st, 2007 to September 2017 were retrospectively reviewed. Only patients with the FIGO diagnosis GTN were included, while those with the histological diagnosis of hydatidiform mole (HM), also sometimes classified as GTD, were not included in this study. Also excluded were all cases with incomplete or missing data. Twenty four patients were included. Median age of patients at the time of diagnosis was 37 years (range 18 - 60). Most patients developed GTN following molar pregnancy (75%), had disease duration from antecedent pregnancy of less than 6 months (58.20%), and had the pre-treatment hCG level more than 10,000 IU/L (58.27%). At diagnosis, 14 patients (58.33%) had localized disease (M0). Most common metastatic sites at initial diagnosis were the liver and brain (20.83%). After a median follow-up from initial diagnosis of six months (range 1 - 24), 58.33% were lost to follow up. This represented an increase in the percentage of patients lost to follow up prior to completion of therapy, when compared with our previous results for an earlier time period. GTN in Malagasy woman displays an aggressive clinic profile. Finding ways to increase treatment compliance provides the best way to minimize recurrences of this potentially deadly disease.

Challenges in the diagnosis and treatment of gestational trophoblastic neoplasia worldwide

Gestational trophoblastic neoplasia(GTN) is a rare tumor that originates from pregnancy that includes invasive mole, choriocarcinoma(CCA), placental site trophoblastic tumor and epithelioid trophoblastic tumor(PSTT/ETT). GTN presents different degrees of proliferation, invasion and dissemination, but, if treated in reference centers, has high cure rates, even in multi-metastatic cases.The diagnosis of GTN following a hydatidiform molar pregnancy is made according to the International Federation of Gynecology and Obstetrics(FIGO)2000 criteria: four or more plateaued human chorionic gonadotropin(hCG)concentrations over three weeks; rise in hCG for three consecutive weekly measurements over at least a period of 2 weeks or more; and an elevated but falling hCG concentrations six or more months after molar evacuation. However,the latter reason for treatment is no longer used by many centers. In addition,GTN is diagnosed with a pathological diagnosis of CCA or PSTT/ETT. For staging after a molar pregnancy, FIGO recommends pelvic-transvaginal Doppler ultrasound and chest X-ray. In cases of pulmonary metastases with more than 1cm, the screening should be complemented with chest computed tomography and brain magnetic resonance image. Single agent chemotherapy, usually Methotrexate(MTX) or Actinomycin-D(Act-D), can cure about 70% of patients with FIGO/World Health Organization(WHO) prognosis risk score ≤ 6(low risk), reserving multiple agent chemotherapy, such as EMA/CO(Etoposide,MTX, Act-D, Cyclophosphamide and Oncovin) for cases with FIGO/WHO prognosis risk score ≥ 7(high risk) that is often metastatic. Best overall cure rates for low and high risk disease is close to 100% and > 95%, respectively. The management of PSTT/ETT differs and cure rates tend to be a bit lower. The early diagnosis of this disease and the appropriate treatment avoid maternal death,allow the healing and maintenance of the reproductive potential of these women.

Effect of hypoxia on expression of placental trophoblast cells SATB1 and β-catenin and its correlation with the pathogenesis of preeclampsia

Objective: To study the effect of hypoxia on the expression of placental trophoblast cells SATB1 and β-catenin and its correlation with the pathogenesis of preeclampsia. Methods: Trophoblastic cell lines HRT8/SVneo were cultured, SATB1 and β-catenin expression and cell biological behavior were determined after hypoxia reoxygenation treatment; cell biological behavior and the expression of related genes were determined after the transfection of SATB1 and β-catenin siR NA; preeclampsia placenta and normal placenta tissues were collected and the expression of SATB1 and β-catenin were determined. Results: OD value, cell migration rate, m RNA contents of SATB1 and β-catenin of H/R group were significantly lower than those of Nor group, cell apoptosis rate was higher than that of Nor group and the number of invasive cells was less than that of Nor group; OD value and bcl-2 mRNA content of SATB1-siRNA group were lower than those of NC group; cell apoptosis rate as well as Bax, Caspase-3, caspase-6 and caspase-9 mRNA contents were higher than those of NC group; cell migration rate as well as CTSB, CTSD, MMP2 and MMP9 mRNA contents of β-catenin-siRNA group were lower than those of NC group; the number of invasive cells was less than that of NC group; the expression levels of SATB1 and β-catenin in preeclampsia placenta tissue were significantly lower than those in normal placenta tissue. Conclusions: Hypoxia can inhibit the expression of SATB1 and β-catenin in the pathogenesis of preeclampsia, which can affect the proliferation, apoptosis, migration and invasion of cells.

Effects of maternal diabetes on trophoblast cells

Diabetes mellitus(DM)is a health condition characterized by hyperglycemia over a prolonged period.There are three main types of DM:DM type 1(DM1),DM2 and gestational DM(GDM).Maternal diabetes,which includes the occurrence of DM1 and DM2 during pregnancy or GDM,increases the occurrence of gesttional complications and adverse fetal outcomes.The hyperglycemic intrauterine environment affects not only the fetus but also the placental development and function in humans and experimental rodents.The underlying mechanisms are still unclear,but some evidence indicates alterations in trophoblast proliferation,apoptosis and cell cycle control in diabetes.A proper coordination of trophoblast proliferation,differentiation and invasion is required for placental development.Initially,increased expression of proliferative markers in junctional and labyrinth zones of rat placentas and villous cytotrophoblast,syncytiotrophoblast,stromal cells and fetal endothelial cells in human placentas is reported among diabetics.Moreover,reduced apoptotic index and expression of some apoptotic genes are described in placentas of GDM women.In addition,cell cycle regulators including cyclins and cyclin-dependent kinase inhibitors seem to be affected by the hyperglycemic environment.More studies are necessary to check the balance between proliferation,apoptosis and differentiation in trophoblast cells during maternal diabetes.

Expression and Immune Effect of Toll-Like Receptor 4 in Human Trophoblast Cells

This study investigated the expression and immune effect of TLR4 in human trophoblast cells. The expression level of TLR4 mRNA in normal and LPS-stimulated human term trophoblast cells （1 mg/L LPS, 12 h） was detected by RT-PCR. In LPS-stimulated human term trophoblast cells of TLR4-blocked group and non-TLR4-blocked group, and normal term trophoblast cells of blank control group, apoptosis rate was measured by flow cytometry （FCM）, and the level of TNF-α determined by using enzyme linked immunosorbent assay （ELISA） respectively. RT-PCR results showed that the expression level of TLR4 mRNA in LPS-stimulated human trophoblast cells was significantly higher than that in normal cells （P〈0.01）. FCM revealed that there was significant difference in apoptosis rate of LPS-stimulated human term trophoblast cells between TLR4-blocked group and non-TLR4-blocked group （P〈0.05）, or between TLR4 antibody-blocked group and blank control group. ELISA indicated that the level of TNF-α in LPS-stimulated human trophoblast cells also had statistical differences between TLR4 antibody-blocked group and non-TLR4 antibody-blocked group （P〈0.05）. Our results suggest that TLR4 plays an important role in the immunological mechanism of apoptosis and secretion of TNF-α of human term trophoblast cells stimulated by LPS.

IL-24 Expression at Maternal-fetal Interface and Its Roles in Trophoblast Invasion

In this study, the expression of IL-24 at maternal-fetal interface and the roles in extravillous trophoblast （the TEV-1 cell line） invasion were examined. Immunohistochemistry was used to detect the expression of IL-24 in villi and decidual tissue. The proliferation of TEV-1 cells under the effect of IL-24 was measured by MTT assay. The invasiveness of TEV-1 cells under the effect of recombinant IL-24 （rhIL-24） was examined by transwell system. Immunohistochemical detection showed that IL-24 was expressed in the villi and decidual tissue, and distributed in villous column, trophoblasts, stroma and blood vessels. The proliferation of TEV-1 cells was not inhibited by rhIL-24 of various concentrations. The examination of invasion in vitro showed that rhIL-24 could inhibit the invasion of TEV-1 cells in a concentration-dependent manner. The results suggested IL-24 could inhibit the invasion of TEV-1 cells. Therefore, IL-24 produced by maternal-fetal interface in human first trimester pregnancy may influence the invasion of trophoblasts and is involved in normal pregnancy.

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.

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.

A COMPARATIVE STUDY OF TRANSVAGINAL ULTRASONOGRAPHY AND PELVIC ARTERIOGRAM IN ASSESSMENT OF PATIENTS WITH GESTATIONAL TROPHOBLASTIC TUMOUR

Objective:To compare the reliability of transvaginal ultrasonography with pelvic arteriography in the assessment of patients with gestational trophoblastic disease. Methods. Transvaginal ultrasonography was performed in 24 patients with gestational trophoblastic tumour. Within one week after ultrasound investigation, pelvic arteriography was carried out in each patient. Of 24 cases, 16 patients hadn’t been treated by chemical reagent, 5 had accepted 2 to 5 courses of chemotherapy, and 3 had achieved complete remission before both investigations performed. Results. In 3 patients with complete remission, 2 had no evidence of abnormal findings either on transvaginal ultrasonography or on pelvic arteriography, 1 showed intramyometrial lesions by both methods. In the remaining 21 patients, all demostrated a abnormal uterine image, and 5 of them accompanied with the finding of parametrium metastatic signs by transvaginal ultrasonography; these abnormal results were confirmed by pelvic arteriographic imaging. However, in two cases without clinical and ultrasonic signs of parametrium metastasis, pelvic arteriography indicated the early metastasis of parametrium ves- sels. Conclusions. Even though it is difficult to predict the early parametrium metastasis in patients with gestational trophoblastic disease by B-ultrasonic investigation, our data would support the introduction of transvaginal ultrasonography in the diagnosis and evaluation of gestational trophoblastic tumour.

THE ROLE OF HYSTERECTOMY IN THE THERAPY OF GESTATIONAL TROPHOBLASTIC TUMOR

To evaluate the role of hysterectomy for patients with gestational trophoblastic tumor. [WT5”BX]Methods.[WT5”BZ]We retrospectively analyzed 68 cases of gestational trophoblastic neoplasia treated by hysterectomy from 1985～1997 at PUMC hospital. Thirty eight cases were diagnosed of choriocarcinoma and 30 were invasive mole. [WT5”BX]Results.[WT5”BZ]Twenty three elder patients who didn’t desire to preserve fertility were selected for hysterectomy after shorter courses of chemotherapy, 22 of them had a complete remission(95 6%), the total aver age courses of chemotherapy was 4 2. Of twenty seven chemorefractory cases who were suspected of a refractory isolated lesion in the uterus, delayed hysterectomy as an adjunct to chemotherapy was performed, 20 of them got a complete remission(74 1%), the total average courses of chemotherapy were 9 4. Emergency hysterectomy is indicated in 18 patients with uterine perforation or life threatening hemorrhage, 17 cases had a complete remission(94 4%), the total average courses of chemotherapy were 7 6. [WT5”BX]Conclusion.[WT5”BZ]Although the development of effective chemotherapy has resulted in improved survival of patients with gestational trophoblastic tumor, hysterectomy remains an important adjuncts in the treatment of a selected subset of patients; in order to operate more completely and prevent recurrence, it’s better to perform extended hysterectomy for the indicated patients.

EXPRESSION OF P53 PROTEIN AND PROLIFERATING CELL NUCLEAR ANTIGEN IN HUMAN GESTATION TROPHOBLASTIC DISEASE

To study the relationship between p53 protein, proliferating cell nuclear antigen (PCNA) expression and benign or malignant gestational trophoblastic disease (MGTD). Methods: The histotomic sections of 48 patients with gestational trophoblastic disease and 24 patients of normal chorionic villi were stained using immunohistochemistry. The monoclonal antibodies were used to determine p53 protein and PCNA. Results: The frequency of p53 and PCNA positive expression were significantly different among the chorionic villi of normal pregnancy, hydratidiform mole (HM) and MGTD. But neither p53 nor PCNA has any relation with the clinical staging or metastasis of MGTD. Conclusion: Both P53 and PCNA are valuable in diagnosis of human gestational trophoblastic disease.

Tissue factor expression and methylation regulation in differentiation of embryonic stem cells into trophoblast

Objective:To explore tissue factor(TF)expression and methylation regulation in differentiation of human embryonic stem cells(hESCs)into trophoblast.Methods:Differentiation of hESCs into trophoblast was induced by bone morphogenetic protein 4(BMP4).Expression of gene,protein of TF and DNA methylation at different time points during induction process was detected by RTPCT,Western blot,flow cytometry and MSP-PCR method.Results:The expression of mRNA,protein level of TF could be detected during directional differentiation of hESCs to trophoblast cells,semi methylation-semi non methylation expression appeared at TF DNA promoter region,and it showed decreased methylation level and increased non methylation level with formation of trophoblast cell and increased expression of TF.Conclusions:It shows that during differentiation of hESCs into trophoblast,the differential expression of TF is related with DNA methylation level,and it is changed with the methylation or non methylated degree.It provids new platform to furtherly explore the regulation mechanisms of specific expression of tissue factor in the process of the embryonic stem cell development.

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.

In vitro Study on Human Trophoblast Cells Infected with HCMV

Human trophoblast cells were isolated and cultured in vitro in order to investigate possible pathogenesis of intrauterine infection caused by HCMV.Trophoblast cells were obtained by compound enzymes digestion and discontinuous percoll gradient.Cells and purity were identified by using immunocytochemistry assay with anti-CK7,Vim and β-hCG antibodies.HCMV AD169 strain replication in isolated trophoblast cells and cell apoptosis were detected at different time points post infection(p.i.).The results showed tha...

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.