Molar Tissue Research Articles

Retained Molar Tissues: A Clinical Dilemma

Abstract Background: Hysteroscopic resection of retained molar tissues is a safe procedure that can be considered as an alternative option to conventional nonselective blind suction curettage. Case: A 33-year-old woman, gravida 1, para 0, had retained molar tissues after conventional suction evacuation. This retention was treated with hysteroscopic resection of the retained molar tissue and chemotherapy. Results: This patient had an unremarkable follow-up course. Conclusions: This case highlights the utilization of various modalities, such as ultrasound, immunostaining for the presence of Ki-67, and ultrasound-guided curettage to arrive at the correct diagnosis and management. (J GYNECOL SURG 30:244)

NLRP7 inter-domain interactions: the NACHT-associated domain is the physical mediator for oligomeric assembly.

Mutations in NLRP7 (NOD-like-receptor family, pyrin domain containing 7) are responsible for a type of recurrent pregnancy loss known as recurrent hydatidiform mole (HYDM1). This condition is characterized by abnormal growth of the placenta, a lack of proper embryonic development and abnormal methylation patterns at multiple imprinted loci in diploid biparental molar tissues. The role of NLRP7 protein in the disease manifestation is currently not clear. In order to better understand how the effects of HYDM1 are associated with mutations on the structure of NLRP7, we performed an inter-domain interaction screen using a yeast two-hybrid system. Additionally, we generated in silico structural models of NLRP7 in its non-activated and activated forms. Our observations from the yeast two-hybrid screen and modeling suggest that the NACHT-associated domain (NAD) of the NLRP7 protein is central to its oligomeric assembly. Upon activation, the NAD and a small part of the leucine rich repeat (LRR) of one molecule emerged out of the protective LRR domain and interact with the NACHT domain of the second molecule to form an oligomer. Furthermore, we investigated the molecular basis for the pathophysiological effect of four missense mutations, three HYDM1-causing and one rare non-synonymous variant, on the protein using confocal microscopy of transiently transfected NLRP7 in HEK293T cells and in silico structural analysis. We found that with the two clinically severe missense mutations, L398R and R693W, the normal molecule to molecule interaction was apparently affected thus decreasing their oligomerization potential while aggresome formation was increased; these changes could disturb the normal downstream functions of NLRP7 and therefore be a possible molecular effect underlying their pathophysiological impact.

Hysteroscopy in Pregnancy-Related Conditions: Descriptive Analysis in 273 Patients

Study ObjectiveTo describe the feasibility of office hysteroscopy in patients with pregnancy-related problems such as retained trophoblastic tissue, persistent molar tissue, pregnancy with in situ intrauterine device (IUD), isthmocele, embryoscopy, and osseous metaplasia. DesignRetrospective cohort chart review of use of hysteroscopy in 273 patients with pregnancy-related conditions (Canadian Task Force classification II-2). SettingUniversity tertiary-care hospital. PatientsOffice hysteroscopy with the indication of pregnancy-related conditions such as retained trophoblastic tissue, pregnancy with IUD, molar pregnancy, cesarean scar defects, and fetal death were studied. The study included 273 patients: 185 with retained trophoblastic tissue, 14 with persistent molar tissue, 7 with an in situ IUD, 22 with symptomatic isthmocele, 41 with embryoscopy, and 4 with osseous metaplasia. InterventionDiagnostic and operative office hysteroscopy. Measurements and Main ResultsVariables studied included resolution of abnormal uterine bleeding in patients with persistent trophoblastic tissue, normalization of β-human chorionic gonadotropin levels in patients with persistent molar tissue, continuation of pregnancy after retrieval of lost IUDs, resolution of postmenstrual bleeding in patients with symptomatic isthmocele, rate of uncontaminated embryonic tissue after embryoscopic biopsy, and successful extraction of bony tissue in patients with osseous metaplasia. Office hysteroscopy enabled resolution of most cases of retained trophoblastic tissue (91.8%) and all 14 cases of persistent molar tissue. 7 IUDs were extracted from pregnant patients. Fifteen isthmoceles resolved with office hysteroscopy, and 7 were resected in the operating room. A normal karyotype was obtained in 37 embryoscopies (90.2%). Four osseous metaplasia cases resolved with either office hysteroscopy (75%) or resectoscopy in the operating room (25%). ConclusionOffice hysteroscopy is a safe and minimally invasive treatment for pregnancy-related conditions, with good clinical and functional results.

A pre-clinical murine model of oral implant osseointegration

Many of our assumptions concerning oral implant osseointegration are extrapolated from experimental models studying skeletal tissue repair in long bones. This disconnect between clinical practice and experimental research hampers our understanding of bone formation around oral implants and how this process can be improved. We postulated that oral implant osseointegration would be fundamentally equivalent to implant osseointegration elsewhere in the body. Mice underwent implant placement in the edentulous ridge anterior to the first molar and peri-implant tissues were evaluated at various timepoints after surgery.Our hypothesis was disproven; oral implant osseointegration is substantially different from osseointegration in long bones. For example, in the maxilla peri-implant pre-osteoblasts are derived from cranial neural crest whereas in the tibia peri-implant osteoblasts are derived from mesoderm. In the maxilla, new osteoid arises from periostea of the maxillary bone but in the tibia the new osteoid arises from the marrow space. Cellular and molecular analyses indicate that osteoblast activity and mineralization proceeds from the surfaces of the native bone and osteoclastic activity is responsible for extensive remodeling of the new peri-implant bone. In addition to histologic features of implant osseointegration, molecular and cellular assays conducted in a murine model provide new insights into the sequelae of implant placement and the process by which bone is generated around implants.

Novel NLRP7 mutations in familial recurrent hydatidiform mole: are NLRP7 mutations a risk for recurrent reproductive wastage?

ObjectiveFamilial recurrent hydatidiform mole is an exceedingly rare clinical condition. Affected women are predisposed to molar pregnancies of diploid, biparental origin rather than androgenetic origin. At present, NLRP7 and KHDC3L (C6orf221) are the only genes known to be associated with familial recurrent hydatidiform mole. This study investigated the genetic dispositions in two large Turkish families with recurring molar conceptuses. Study designCopy number variation analysis was performed followed by NLRP7 gene sequencing. The finding of a mono-allelic condition in one family led to investigation of the adjacent NLRP2 gene and recently associated KHDC3L gene. Sampled molar tissues were genotyped using microsatellite markers. ResultsIn one family, a homozygous single nucleotide insertion that caused a frameshift leading to an early stop codon, c.2940_2941insC (p.Glu981ArgfsX13), was identified in the affected sisters. In the other family, a heterozygous 60-kb deletion eliminating substantial portions of the NLRP2 and NLRP7 genes on one allele was found. Screening of NLRP2 and KHDC3L genes revealed no alterations that were considered to be pathological. Genotyping of six independent molar conceptions revealed that five were of diploid, biparental origin and one was of diandric, triploid origin. ConclusionsTwo novel protein-truncating mutations in the NLRP7 gene were found to be associated with familial recurrent hydatidiform mole. Mutations in the NLRP7 gene causing recurrent biparental hydatidiform mole may also be associated with other forms of recurrent reproductive wastage.

Partial molar pregnancy after intracytoplasmic sperm injection occurring as a result of diploid sperm usage

Partial molar pregnancies are rare conceptions characterized by having 69 rather than 46 chromosomes, the additional chromosome complement usually occurring as a result of fertilization of the ovum by two sperm. Although assisted conception with intracytoplasmic sperm injection (ICSI) should prevent the development of a partial molar pregnancy, occasional cases have been described after assisted conception using ICSI. The objective of this study was to investigate the cause of partial molar pregnancy in a couple who had undertaken assisted conception with ICSI. Fluorescent microsatellite genotyping of DNA from the couple and tissue from their partial molar pregnancy was performed in order to confirm diagnosis and investigate the origin of the additional chromosome set. Genotyping confirmed that the partial molar tissue was triploid with an additional chromosome complement from the father. Genotyping of additional loci proximal to the centromere demonstrated that the two paternal sets of chromosomes originated in a single sperm with a double complement of paternal DNA resulting from non-reduction at the second meiotic division. This study confirms that partial molar pregnancy may occur after assisted conception with ICSI and that this occurs as a result of fertilization with a diploid sperm.

Detection of Sugar Chain Expression in Hydatidiform Mole Using Lectin Histochemistry

BackgroundHydatidiform moles carry a significant risk for developing persistent gestational trophoblastic disease. Lectins are useful tools to identify cellular glycosylation pattern and changes in glycosylation that occur during growth, development, differentiation and also, during disease states.ObjectivesConsidering the changes in glycosylation that occur during cell proliferation, differentiation and transformation, the aim of the present study was to evaluate the sugar chain expression in hydatidiform mole by using HRP-conjugated lectins.Materials and MethodsLectin histochemistry with a panel of HRP-conjugated lectins comprising SBA, PNA, VVA, UEA-1, LTA, GS-І (B4) and WGA were performed in 20 molar (partial & complete moles) formalin-fixed, paraffin-embedded tissue samples.ResultsThe partial and complete moles generally showed similar reactivity with all used lectins. None of lectins reacted with villous cytotrophoblasts, whereas 4 of 7 lectins comprising WGA, LTA, UEA-І and PNA (after pretreatment with neuraminidase) showed a moderate to strong reactivity with villous syncytiotrophoblasts in both partial and complete hydatidiform moles. The villous stroma reacted with all used lectins except VVA.ConclusionsOur histochemical findings showed a relatively heavy glycosylation of syncytiotrophoblasts of both partial and complete molar tissues, which was prominent in apical portion. This may play a role in their capacity to increase trophoblastic proliferation.

Complete mole in a dichorionic twin pregnancy after intracytoplasmic sperm injection

A dichorionic twin pregnancy with complete hydatidiform mole and coexistent fetus is a rare and challenging situation, whose pathogenesis has not been yet fully understood. We present a case of a 39-year-old woman who underwent intracytoplasmic sperm injection with two embryos transfer. The 12-week gestation ultrasound examination revealed normal fetus and placenta with features of hydatidiform mole, leading to pregnancy termination. Autopsy and histological examinations diagnosed a complete mole coexisting with a normal fetus, and the genetic analysis showed a diploid fetus with biparental genome and molar tissue with paternal diploidy. This case highlighted that complete molar pregnancies may still occur even though pregnancy is achieved after intracytoplasmic sperm injection. A review of the literature was performed by collecting data from the few similar reported cases and by commenting on the pathogenesis of this rare condition.

Diagnostic value of lectins in differentiation of molar placentas.

Distinction of hydatidiform moles from non-molar specimens and subclassification of hydatidiform moles as complete and partial are important for clinical practice, but diagnosis based solely on histomorphology suffers from poor interobserver reproducibility. Nowadays, pathologists rely on molecular techniques, however these methods are technically difficult, relatively expensive, and time consuming, and cannot be applied in all laboratories. Therefore, a relatively easy, time- and cost-effective ancillary tool, would be helpful. This study aimed to assess the role of lectins in differential diagnosis of molar placentas. Lectin histochemistry with a panel of HRP-conjugated lectins comprising SBA, DBA, MPA, PNA, VVA, UEA-1, LTA, GS-І (B4), and WGA were performed in 20 non-molar (hydropic and non-hydropic spontaneous abortions) and 20 molar (partial and complete moles), formalin-fixed paraffin-embedded tissue samples. On the basis of staining intensity, sections were graded and Kruskal-Wallis non-parametric statistical test was used to compare differences between samples. There was a significant difference between the reactivities of LTA and UEA-І with syncytiotrophoblasts of molar and non-molar specimens (P<0.001). These lectins generally showed a moderate reactivity with syncytiotrophoblasts of molar group but did not react with this cell population in non-molar group. Furthermore, WGA showed relatively increased reaction with syncytiotrophoblasts of molar tissues compared with abortions, however, this did not reach to statistical significance (P=0.07). No major differences were seen in other lectins reactivities between the studied groups. The present study showed that UEA-1 and LTA lectins may be used as cytochemical probes in differentiating molar from non-molar placentas, but did not differentiate partial moles from complete moles.

Nanoporous anodic oxidation titanium enhances cell proliferation and differentiation of immortalized mouse embryonic cells

Biological integration of dental implants into the surrounding tissue determines clinical success and the attraction of bone cells. Titanium and its alloys are widely used biomaterials with high mechanical strength and excellent biocompatibility; nanotopographies are currently under investigation for efficiency in promoting cell functions. The purpose of this study was to carry out nanoporous anodic oxidation (NAO) surface treatment on titanium and to observe the responses of immortalized mouse embryonic (ME) cells. The titanium surface was modified in two ways; by NAO via hydrofluoric acid and by microporous anodic oxidation (MAO). The ME cells were solely obtained from mesenchymal mouse (embryonic day 14.5) molar tissue (tooth germ). Field emission scanning electron microscopy was used to visualize the titanium surface morphology as well as the attachment and morphological features of the ME cells. Cytotoxicity, cell proliferation, and alkaline phosphatase activity were assayed as well. The nano- and microporous structures of the modified titanium surfaces were well formed, with diameters of 100nm and 1–3μm, respectively. ME cells were well attached to the NAO and MAO treated surfaces, resulting in no cytotoxicity to ME cells. Cell proliferation was significantly higher for the cells at the NAO treated surface than cells at the MAO treated surface. Alkaline phosphatase activity on the NAO treated surface increased from 1 to 3weeks. Hence it was concluded that NAO treated surfaces provide an attractive substrate for ME cell adhesion, proliferation, and differentiation, and may serve as useful materials for the construction of dental implants.

LOW DOSES OF HIGH FREQUENCY LOW MAGNITUDE LOADING INCREASE MODULUS & MAINTAIN GAG IN CULTURED TENDONS

Objective: The purpose of this study was to evaluate the association of telomerase activity in complete hydatidiform moles with subsequent development of persistent gestational trophoblastic tumor. Study Design: By means of the standard telomerase repeat assay, we examined telomerase activity in 4 normal placentas, 31 complete hydatidiform moles (16 cases of uneventful regression, according to serum levels of β-human chorionic gonadotropin, after evacuation and 15 cases in which persistent gestational trophoblastic disease developed after evacuation), 7 invasive moles, and 5 choriocarcinoma tissue samples. Results: Telomerase activity was detected in 13 of 15 (86.7%) complete hydatidiform moles in patients who eventually underwent chemotherapy for the treatment of persistent gestational trophoblastic tumors. All 9 patients with metastatic disease (International Federation of Gynecology and Obstetrics stage III) had telomerase activity in the initial molar tissue sample. In contrast, telomerase activity was evident in only 3 of 16 (12.5%) complete hydatidiform moles from patients with spontaneous remission after evacuation (P < .05). Telomerase activity was detected in all 7 invasive moles and all 5 choriocarcinoma tissue samples but was not detected in normal placentas. Conclusion: The presence of telomerase activity in complete hydatidiform moles is associated with the development of persistent gestational trophoblastic tumors, such as invasive moles and choriocarcinoma. (Am J Obstet Gynecol 1999;180:328-33.)

Suppression of Hydatidiform Molar Growth by Inhibiting Endogenous Brain-Derived Neurotrophic Factor/Tyrosine Kinase B Signaling

Brain-derived neurotrophic factor (BDNF)/tyrosine kinase B (TrkB) receptor signaling promotes trophoblast growth in normal and abnormal pregnancy. It also regulates the growth of malignant trophoblastic, choriocarcinoma cells. However, possible involvement of this signaling system in hydatidiform mole, another major gestational trophoblastic disease, has not been determined. Here, we found the expression of BDNF in syncytiotrophoblasts and its receptor, TrkB, in cytotrophoblasts of hydatidiform mole using real-time RT-PCR and immunoassays. In molar explant cultures, treatment with soluble TrkB ectodomain or a Trk receptor inhibitor K252a inhibited trophoblast outgrowth as well as decreased cytotrophoblast proliferation and cellular viability based on histopathological analyses and glucose metabolism monitoring. These inhibitors also increased apoptosis and caspase-3/7 activities. In an in vivo model of hydatidiform molar growth based on xenotransplantation of molar tissues into kidney capsules of SCID mice, treatment with K252a suppressed molar growth as reflected by decreased trophoblast proliferation and their invasion into mouse kidney, reduced tissue levels of chorionic gonadotropin-β, and increased apoptosis. Based on PCR array analyses to identify changes in expression profiles of cell cycle- and apoptosis-related genes in cultured molar explants, suppression of endogenous TrkB signaling led to decreases in key cell cycle-stimulatory and checkpoint genes together with the down-regulation of different antiapoptotic genes. Our findings demonstrate the importance of paracrine signaling by the BDNF/TrkB system in the proliferation and survival of molar trophoblasts. Inhibition of BDNF/TrkB signaling could provide a novel medical treatment for hydatidiform mole.

Mutations in NLRP7 are associated with diploid biparental hydatidiform moles, but not androgenetic complete moles

BackgroundNLRP7 (NALP7) has been identified as the major gene involved in the inherited predisposition to recurrent molar pregnancies, a rare recessive condition in which affected individuals have complete hydatidiform moles...

667C > T and 1298A > C polymorphisms of MTHFR do not predict response to methotrexate in patients with gestational trophoblastic neoplasia

Objective Approximately one third of patients treated with methotrexate for gestational trophoblastic neoplasia (GTN) following a molar pregnancy are reported to develop resistance to methotrexate and need to change to different chemotherapeutic agents. Previous studies, in other clinical settings, have suggested that polymorphisms in key folate metabolising enzymes such as 5,10-methylenetetrahydrofolate reductase (MTHFR) influence both toxicity and efficacy of methotrexate. Our objective was to investigate the impact of two common functional MTHFR polymorphisms, 677C > T and 1298A > C, on the efficacy of methotrexate in women treated for GTN following a molar pregnancy. Methods DNA from 121 women treated with methotrexate for GTN was genotyped for the 677C > T and 1298A > C polymorphisms using TaqMan SNP Genotyping Assays. In 64 cases these polymorphisms were also genotyped in the antecedent molar pregnancy, using DNA extracted from archival blocks of tissue. Response to methotrexate was evaluated with reference to serial human chorionic gonadotrophin (hCG) levels in patient serum. Results No significant association was found between the genotype of the patient, or presence of the variant allele, and clinical response to methotrexate therapy for either the 677C > T or the 1298A > C SNP. No significant association was found between the genotypes of the molar tissue and response to methotrexate. In molar tissue there was a significant reduction in the expected number with the 677TT genotype suggesting the 677C > T SNP may identify a subgroup of molar pregnancies less likely to progress to GTN. Conclusion Neither the genotype for the 677C > T SNP or the 1298A > C SNP in MTHFR predict the therapeutic outcomes of women treated with single agent methotrexate for GTN.

Expression and significance of LMP2 and PPM1A in gestational trophoblastic disease

To investigate the expression of low molecular mass polypeptide-2 (LMP2) and protein phosphatase 1A (PPM1A) in gestational trophoblastic disease and elucidate their predictive value in malignant transformation of hydatidiform mole. The expressions of LMP2 and PPM1A protein in 196 complete hydatidiform moles (in which 28 cases with malignant transformation), 7 invasive moles, 5 choriocarcinomas and 20 normal chorionic villus were detected with the method of EnVision immunohistochemistry. Their clinicopathologic data were retrospectively analyzed. LMP2 and PPM1A protein expressed in cytotrophocytes, syncytiotrophoblast and extravillous trophoblast. The level of LMP2 expression in deteriorative hydatidiform mole was significantly higher than that in non-deteriorative hydatidiform mole or normal chorionic villus (6.79±2.38, 5.26±2.63 and 3.10±1.65, all P<0.01), while there were no difference compared with gestational trophoblastic neoplasms (6.42±2.68, P=0.113). The level of PPM1A expression was highest in normal chorionic villus, and decreased gradually in hydatidiform mole (non-deteriorative and deteriorative) and gestational trophoblastic neoplasms (6.30±2.98, 4.93±2.50, 4.43±2.04 and 3.33±2.06, all P<0.01); the level of PPM1A expression in deteriorative hydatidiform mole was significantly lower than that in non-deteriorative hydatidiform mole (P=0.001). The expression of LMP2 protein was correlated to theca lutein ovarian cyst, the expression of PPM1A protein was related with uterine size (P<0.05). While, there was no correlation between the expressions of the two proteins (P>0.05). High expression of LMP2 and low expression of PPM1A might play an important role in the motility and invasiveness of trophoblast cells and malignant transformation of hydatidiform mole. Testing the expression of LMP2 and PPM1A in hydatidiform mole tissues of initial uterine evacuation might be have some reference significance in judging outcomes of hydatidiform mole.

The genetics of recurrent hydatidiform moles in China: correlations between NLRP7 mutations, molar genotypes and reproductive outcomes

Hydatidiform mole (HM) is a human pregnancy with abnormal embryonic development. NLRP7 is a major autosomal recessive gene responsible for recurrent molar pregnancies and associated reproductive wastage in patients from several populations. Here, we report NLRP7 mutation analysis in 35 unrelated Chinese patients with recurrent reproductive wastage, including at least one HM. We describe three new protein-truncating mutations in NLRP7 and show the presence of three founder mutations in China and Asian populations. We determined the parental contribution to six molar tissues and show the occurrence of three diploid androgenetic moles in patients with one defective allele, while three diploid biparental moles occurred in patients with two defective alleles. We document the failure of pregnancies after assisted reproductive technologies (ARTs) in three patients with two defective alleles each and a successful pregnancy in one of two patients with one defective allele. Our data suggest that patients with a single defective allele have better reproductive outcomes than patients with two defective alleles, and some of them may benefit from ART.

Recurrent triploid and dispermic conceptions in patients with NLRP7 mutations

To understand the mechanisms leading to hydatidiform mole formation in patients with NLRP7 mutations, we used a combination of various approaches to characterize five products of conception, from two patients, shown by flow cytometry to contain non-diploid cells. We demonstrate that four of these conceptions are triploid and two of them originated from fertilization with more than one sperm. We show that three of these triploid conceptions fulfill the histopathological criteria of partial hydatidiform mole and one fulfills the histopathological criteria of spontaneous abortion. Our data demonstrate that some oocytes from one patient with NLRP7 mutations are not able to prevent polyspermic fertilization and highlight the importance of using several approaches to characterize the genetic complexity of molar tissues and reproductive wastage. Altogether, our previous and current data show the association of NLRP7 mutations with several types of hydatidiform moles and with triploid spontaneous abortions.

Molecular Distinction of Consecutive Molar Pregnancies

It may be difficult to differentiate the consecutive occurrence of two independent molar pregnancies from gestational trophoblastic neoplasia after the initial molar pregnancy, especially when the interval between them is short. A 25-year-woman who had had a complete hydatidiform mole 6 months earlier presented with a 6-week history of secondary amenorrhea. Serum human chorionic gonadotropin had increased to 19,857 micro-international units/mL, with no gestational sac demonstrated. Dilation and curettage was performed. Pathologic examination identified a tiny amount of hydropic villi compatible with complete hydatidiform mole. Analysis of short tandem repeat polymorphisms revealed that the molar tissues of the first and second complete hydatidiform moles were of different genetic origin. The patient went into remission spontaneously without chemotherapy. Genetic profiling was useful to discriminate a recurrent mole from suspected gestational trophoblastic neoplasia.

Hydatidiform mole mimicking an enlarged uterine fibromyoma four months after ART

AbstractHydatidiform mole is a pregnancy disorder, of a benign nature. We present a case of molar tissue within a uterine myoma, the first such entity reported in the literature. In May 2006, a thirty-eight year old infertility patient was admitted for myomectomy. She had anamnesis for chronic pelvic inflammatory disease and surgeries performed for tubal pregnancies. After the sixth intracytoplasmal spermatozoa injection procedure performed in January 2006, she conceived, but curettage was performed in March 2006 for a missed abortion. Following the routine preoperative evaluation in May 2006, four months after the last artificial reproductive technology procedure, myomectomy was performed as uneventful operation, but the histological report appeared unusual, showing degenerated chorionic villi within the uterine myoma. Molar tissue within uterine myoma might evolve even after artificial reproductive procedures. Furthermore, this finding might be misinterpreted as a fibromyoma degeneration. This is the first, and a unique case, of molar tissue within uterine myoma reported in the literature.

T9.3 Decidual cell surface and secreted factors regulate extravillous trophoblast function: important implications in placental development

Integrins are heterodimeric glycoproteins acting as membrane receptors for extracellular matrix components. The specificity of these receptors towards one particular matrix glycoprotein depends on the type of α and β subunit combination. Since integrins are involved in the migratory behaviour of cells and since cytotrophoblastic cells are constitutively invasive, we undertook to immunolocalize the α2, α5 and α6 integrin subunits in normal and hydatidiform molar trophoblast, in an implantation site as well as in decidualized and non-decidualized endometrium. α6 positivity was confined to villous cytotrophoblast and was clearly polarized towards the basement membrane. Extravillous cytotrophoblastic cells were α6-negative but became α5-positive. In contrast to normal trophoblast, villous cytotrophoblast from hydatidiform molar tissue was α5-positive. We conclude that the expression of a α5 integrin subunit on cytotropholastic cell surfaces is correlated with the appearance of an invasive phenotype. α6 and α2 integrin subunits were both localized on the surface and glandular epithelium of the endometrium and their expression was increased during the secretory phase but became low or undetectable after decidualization. In contrast, α5 subunit positivity was weak in the same epithelia during the first half of the cycle but disappeared after ovulation. Stromal cell α5 positivity was present throughout the cycle but increased dramatically in decidualized endometria. We conclude that the α5 integrin subunit which disappears from the epithelium at the end of the cycle might allow migration of the epithelial cells and repair of the endometrium after menses. We also wonder if α5 positivity is part of a change in the stromal cell phenotype induced by decidualization.