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PubMed1992

[Polyploidy and polyteny in the trophoblast cells of the mink].

According to cytophotometry, trophoblast cells in the mink placenta are both diploid and polyploid, the ploidy level ranging from 2c to 64c. A great number of mink trophoblast cells were seen to divide mitotically. In addition to the ordinary mitotic figures, polyploid mitoses as well as abnormal mitotic figures were observed. Non-classic polytene chromosomes, peculiar to the mammalian trophoblast, appeared in the mink trophoblast cells to have the highest ploidy. A relatively low ploidy degree is due, probably, to a lesser invasive activity of the mink trophoblast cells as compared to the rodent giant trophoblast cells.

Animals↗
PubMed1992

[Trophoblast: its functional regulation and pathophysiological profiles].

The trophoblast of the human placenta is composed of two layers: syncytiotrophoblast and cytotrophoblast. Cytotrophoblast displays highly proliferative and invasive properties, while syncytiotrophoblast displays little potential for proliferation. Regulatory factors involved in processes of proliferation and differentiation of the trophoblast still remain to be elucidated. Immunohistologically, myc product was predominantly localized to cytotrophoblastic cells. A close similarity between cytologic localization of myc product and tritiated thymidine labeling of placental explant suggests that myc protein expression is linked to trophoblast proliferation. A similar pattern of cytological localization was observed with the use of anti-PDGF antibody, supporting a possibility that PDGF also plays a role in the trophoblast proliferation. Human trophoblast produces two major proteins, hCG and hPL. hCG stimulates progesterone production by corpus luteum. hPL exerts lipolytic action which assures glucose supply to the fetus. In situ hybridization with cDNA probes for hCG(alpha, beta) and hPL revealed that mRNA expression of hCG alpha and probably hCG beta are initiated before syncytial formation, whereas hPL mRNA is expressed only in fully differentiated syncytiotrophoblast. hCG levels in maternal serum are the highest in early pregnancy and thereafter decline, while hCG alpha and hPL levels increase throughout pregnancy. In patients with choriocarcinoma, serum hPL levels are extremely low despite high levels of hCG. In this context, hCG beta mRNA levels remarkably declined in term placenta compared to early placenta, and hPL mRNA was little observed in choriocarcinoma. EGF and EGF receptor (EGF-R) in 4-5 weeks placenta were almost exclusively localized to cytotrophoblasts, whereas EGF and EGF-R in 6-12 weeks placenta were predominantly localized to syncytiotrophoblasts. In the second and third trimester placentas, EGF was mainly localized to cytotrophoblasts, while EGF-R was predominantly localized to syncytiotrophoblasts. It is of great interest that the cytologic localization of EGF and EGF-R in human placenta varies according to the age of gestation. The fact that mitotically active cytotrophoblasts in 4-5 weeks placenta were positive for both EGF and EGF-R expression suggests that EGF and EGF-R may be involved in the control of multiplication of cytotrophoblasts very early in the first trimester. On the other hand, the fact that mitotically inactive syncytiotrophoblasts in 6-12 weeks placenta were positive for both EGF and EGF-R expression suggests that EGF and EGF-R may play a role in the induction of differentiated function of trophoblast in 6-12 weeks gestation. In fact, EGF stimulated hCG and hPL production and secretion by cultured early placental tissues.(ABSTRACT TRUNCATED AT 400 WORDS)

Biomarkers, Tumor↗
PubMed1992

Color Doppler flow as an indicator of trophoblastic activity in tubal pregnancies detected by transvaginal ultrasound.

OBJECTIVE: To evaluate the potential benefits of transvaginal color Doppler in the diagnostic evaluation of tubal pregnancies. METHODS: Fifty-two women with suspected tubal pregnancy were examined by transvaginal ultrasonography and color Doppler. Those with positive scans were referred for exploratory laparoscopy. The area of the tubal pregnancy was examined by color flow imaging and the resistance indexes (RIs) of the artery blood flows were calculated. The pulsatility indexes (PIs) of both uterine arteries were also measured and serum beta-hCG was quantitated. RESULTS: Tubal pregnancy was diagnosed by transvaginal ultrasonography in 38 of the patients. There were two false-negative and two false-positive results. Color flow in the trophoblastic tissue was detected in 50% of the tubal pregnancies, and the mean (+/- standard deviation) RI of the trophoblastic flows was 0.51 +/- 0.12. The RIs of the trophoblastic flows tended to decrease at higher beta-hCG levels, and 88.2% of the cases with detectable trophoblastic flow had beta-hCG above 800 mIU/mL. The average PI of the uterine arteries was 2.28 +/- 0.89. The PIs of the ipsilateral uterine arteries were significantly lower in the patients with trophoblastic flow than in those without it. CONCLUSION: By monitoring trophoblastic activity, color Doppler may differentiate between active and inactive disease and could assist in choosing the correct treatment.

Adult↗
PubMed2003

[Effect of insulin on apoptosis of cultured human trophoblast cells and its mechanism].

AIM: To explore the effect of insulin on apoptosis of cultured human trophoblast cells and its possible mechanism. METHODS: Human trophoblast cells from early pregnancy women were cultured and divided into 3 groups; normal control group; H2O2, treatment group and insulin plus H2O2 treatment group. H2O2 was used to induce apoptosis of trophoblasts cells. Apoptotic rate was detected by flow cytometry. The effects of insulin on Bcl-2 expression and caspase-3 activity were also detected. RESULTS: H2O2 might induce apoptosis of trophoblast cells and typical morphological features of apoptotic cells was observed under electron microscope. Flow cytometry detection exhibited that insulin could reduce markedly H2O2-induced apoptotic rate of trophoblasts cells (P < 0. 01). Bcl-2 expression rate inH,O, treatment group was significantly lower than that in control group (P < 0. 01), while caspase-3 activity was distinctly higher than that in control group (P < 0. 01). CONCLUSION: Insulin could inhibit apoptosis of human trophoblasts cells induced by H2O2, which be may through decreased caspase-3 activity and increased Bcl-2 protein expression.

Apoptosis↗
PubMed2004

Genome multiplication of extravillous trophoblast cells in human placenta in the course of differentiation and invasion into endometrium and myometrium. II. Mechanisms of polyploidization.

Peculiarities of the structure of interphase nuclei, mitotic activity, and Ki-67 protein intranuclear immunolocalization were studied to elucidate mechanisms of genome multiplication in proliferative and differentiating invasive extravillous trophoblast cells in the human placenta. The presence of numerous chromocenters was shown to be a characteristic feature of proliferative cell nuclei of both villous and extravillous trophoblast. At the beginning of extravillous trophoblast cell differentiation, i.e. in the proximal part of cell columns, some amount of cells with large nuclei containing enlarged chromocenters were found. DNA content was measured simultaneously with counting the number of chromocenters in similarly looking nuclei of squash preparations of placental villi. The increase in the ploidy level up to 4c-8c, accompanied by a slight increase in the number of chromocenters being not proportional to the ploidy level and not exceeding the diploid number of chromosomes of the human genome, was demonstrated. This suggests that genome multiplication of extravillous trophoblast cells may be accomplished by endoreduplication. In addition, pictures of endomitosis were seen at early steps of differentiation of EVT cells. The lack of polyploid mitotic figures or any obvious polyploidizing or restitutional mitoses suggests that these are not of considerable importance in genome multiplication of human EVT cells. However, the prevalence of metaphases at the boundary of the distal part of cell columns suggests that restitutional mitoses may be involved, even partly, in human trophoblast cell polyploidization. At later steps of differentiation, i.e. in the distal part of cell columns, the nuclear structure obviously changes, with a uniform "network" chromatin arrangement prevailing, whereas numerous chromocenters and features of endomitosis are no longer seen. The pattern of Ki-67 protein immunolocalization is also changing along the invasive pathway. In the proliferating stem cells and trophoblast cells of the proximal part of cell columns, Ki-67 was localized in the karyoplasm, chromocenters and numerous small nucleoli, whereas in the distal part of cell columns this protein was detected predominantly in 1-2 large nucleoli. The comparative analysis of the literature data on Ki-67 localization at different stages of cell cycle provided another evidence that EVT cells in the course of invasion may switch to the endoreduplication cycle. In agreement with the relevant report on rodent placentation, our present data suggest that acquirement of an invasive phenotype of EVT cells is accompanied by switching from mitotic division to endoreduplication cycle.

Cell Differentiation↗
PubMed2004

Gestational trophoblastic disease.

Gestational trophoblastic disease is a spectrum of pregnancy disorder arising from the placental trophoblastic tissues. It characterised by the secretion of a distinct tumour marker, the beta-HCG. This condition is highly curable even in the presence of metastasis. The incidence of this disease is higher in the Asian population. The major well-established risk factors for gestational trophoblastic disease are advanced maternal age and a past history of gestational trophoblastic disease. Common clinical presentations include vaginal bleeding in early trimester, uterus larger than gestational age, absence of fetal parts after 20 weeks of gestation. Ultrasonography is a reliable non-invasive tool for diagnosis of gestational trophoblastic disease in the clinical setting. All placental tissue following miscarriage or curettage should have histopathological evaluation to exclude gestational trophoblastic disease. Since this group of disorders is one of the highly curable neoplasms, early diagnosis and prompt treatment is necessary.

Female↗
PubMedDate not supplied

Expression of inhibin/activin subunits, sialyl-lewis A (CA 19-9, sLea) and sialyl-Lewis X (sLex) carbohydrate antigens in a hydatidiform mole with persistent polymorphic trophoblastic hyperplasia.

UNLABELLED: The persistence of polymorphic trophoblastic hyperplasia in a hydatidiform mole is an extremely rare condition. Its early diagnosis is essential since such cases can transform into invasive tumours. MATERIALS AND METHODS: The paraffin-embedded biopsies were routinely stained with HE. Immunohistochemical staining reactions were performed with monoclonal antibodies against inhibin-alpha, inhibin-betaA and inhibin-betaB subunits. Additional immunohistochemical reaction was performed with, Sialyl-Lewis A and Sialyl-Lewis X and glycodelin. RESULTS: Large villi and hydatidiform villi with ranging syncyctio- and cytotrophoblasts were seen. Intervillous proliferating trophoblasts showed cell- and nuclear polymorphy with invasion of the myometrium wall. The immunohistochemistry exhibited strong positivity for inhibin-alpha, inhibin-betaA and inhibin-betaB subunits in trophoblastic tissue, while the decidua was negative. Sialyl-Lewis A and Sialyl-Lewis X showed no or minimal focal immunohistochemical reaction. CONCLUSION: A complete hydatidiform mole with hyperplasia and proliferation presents a high risk of developing a persistent (eventually metastatic) trophoblastic disorder and, in up to 15% of the cases, an invasive mole. In 2.5% of the cases it can transform into a choriocarcinoma. Since the inhibin/activin subunits reacted positively with trophoblastic tissue, they might be a useful diagnostic marker for hydatidiform mole with persistence of polymorphic trophoblastic hyperplasia.

Activins↗
PubMed1991

Is oncofetal fibronectin a trophoblast glue for human implantation?

Using an antibody probe specific for the class of fibronectins that contain the oncofetal domain, it was shown that oncofetal fibronectin (onfFN) is present wherever trophoblasts make contact with extraplacental extracellular matrix (ECM). In normal human implantation sites, onfFN was localized to a highly specific region-the ECM connecting extravilous trophoblasts and trophoblastic cell columns to the uterine decidua. This same zone of onfFN was present in an analogous location in extrauterine gestations. Like these in vivo extravillous trophoblasts, isolated cytotrophoblasts in primary culture synthesized and secreted onfFN as they underwent differentiation. Furthermore, when cocultured with an ECM gel, cytotrophoblast aggregates deposited onfFN at cell-ECM contact sites, resembling early implanting trophoblasts in vivo. In the presence of cyclic AMP agonists, onfFN synthesis was inhibited markedly. It is concluded from these results that onfFN is a trophoblast protein that, under cAMP regulation, could mediate implantation and placental-uterine attachment throughout gestation.

Cells, Cultured↗
PubMed1990

Differential expression of human leukocyte antigen-A, -B, and -C locus specific genes in trophoblast and embryonic cells.

Research on the escape mechanism of the fetoplacental unit has focused on the placental trophoblast, which is though to play an important role in the survival of the fetus. There are two major findings in the present study: (a) The expression of human leukocyte antigen (HLA)-A, -B, and -C locus specific genes is greatly reduced in trophoblast cells compared to embryonic cells by Northern blot analysis using locus specific oligonucleotide probes. This is true even though the transcripts detected by a complementary DNA probe, which contains a very conserved sequence present in all members of the HLA gene family, are equally abundant in trophoblast and embryonic cells. (b) When trophoblast cells or embryonic cells are cocultured with peripheral blood lymphocytes from the corresponding female in the presence of recombinant interleukin 2, allogeneic cytotoxic T lymphocytes are generated only in cultures with embryonic cells, and trophoblast cells express the resistance to lysis by the allogeneic cytotoxic T lymphocytes. These results strongly suggest that the reduction in expression of transplantation antigens (HLA-A, -B, and -C) might address the question why maternal tissue does not reject trophoblast cells.

Base Sequence↗
PubMed1990

[Cytofluorometric nuclear DNA analysis and immunohistochemical study on the proliferative activity of the trophoblasts in human early gestation].

Changes in proliferative activity in trophoblastic cells were evaluated in various different sites of implantation. DNA content analysis by cytofluorometry and immunohistochemical study using a monoclonal antibody Ki-67 was performed in 5 cases with a gestation period of 8-9 weeks. The measurement of proliferative activity of trophoblastic cells was analysed in four different sites of implantation: (1) the top of the anchoring villi, (2) the cell column, (3) the intermediate trophoblasts in the decidua basalis and myometrium, and (4) the free villi. A large number of Langhans cells on the top of the anchoring villi (L-cells) were mononuclear and tetraploid. It was demonstrated that the L-cell group had 2C, 4C and 8C peaks and also had a 4C mode. S-phase fraction was also found in the L-cell group. The so-called intermediate trophoblasts (IMT) in the cell column, decidua basalis and myometrium had 2C and 4C peaks and no S-phase fraction. Ki-67 positive cells existed only in the L-cell group. The findings are as follows: 1. The L-cell group had a higher proliferative activity than the other trophoblasts. It was found to have a mononuclear tetraploidy pattern. 2. It is suspected that the cells having 4C DNA content in the IMT originated in the L-cell group. 3. In conclusion, L-cells may differentiate to syncytial trophoblasts and IMT.

Adult↗
PubMed1990

[MHC class I antigen expression by molar trophoblast].

It is an issue for debate why molar tissues are not rejected by an immunologically potent host, since all genes in complete moles and 2/3 genes in partial moles are considered to be paternally derived. Molar trophoblasts are in direct contact with host cells, and therefore HLA expression by these cells may hold the key to the elucidation of the immunological reaction between molar tissues and the host. It has been reported that villous trophoblasts are negative and extravillous trophoblasts are positive for HLA-A, B,C, but the expressed HLA-A,B,C molecule has been noted to lack their polymorphic determinants. We analyzed the reactivity of two monoclonal antibodies to a monomorphic determinant of HLA-A,B,C (W6/32 and Cappel anti-HLA-A,B,C) with molar trophoblasts, using three uteri containing complete moles and two containing partial moles. The reactivity was examined by an indirect immunoperoxidase method. The staining patterns were almost identical in complete moles and partial moles. Villous trophoblasts showed a negative reaction with both antibodies. On the other hand, extravillous trophoblasts exhibited intense staining for W6/32 and negative staining for Cappel anti-HLA-A,B,C, which may suggest that the expression of a constant region as well as a variant region of HLA-A,B,C molecule is incomplete.

Antibodies, Monoclonal↗
PubMed1987

Problems and pitfalls in the histopathologic diagnosis of gestational trophoblastic lesions.

Proliferative lesions of gestational trophoblast pose problems of interpretation and pitfalls in differential diagnosis. Normally an actively proliferative and invasive tissue, healthy trophoblast shares cytologic features with malignant neoplasms. When trophoblastic hyperplasia accompanies macroscopic villous swelling, a diagnosis of hydatidiform mole (HM) is in order. Exuberant and atypical avillous trophoblast characterizes choriocarcinoma (CCA) and placental site trophoblastic tumor (PSTT). The distinction between them rests on the dimorphic composition of CCA as contrasted with the relative monomorphism of PSTT. Immunohistochemical studies contribute to the latter differential diagnosis. Unfortunately, two common conditions share morphologic features with the major lesions of gestational trophoblast. The hydropic abortus may resemble HM; the banal implantation site in normal early pregnancy and later spontaneous abortion may suggest either CCA or PSTT. Familiarity with the normal and benign variants of chorionic epithelium and thorough tissue sampling may be helpful in difficult cases. Ambiguous lesions that do not conform to conventional classification should be referred for consultation. A few, however, will not fit neatly into diagnostic categories. In such instances, a descriptive report and clear communication with the patient's physician provide the best current approach to clinical follow-up.

Choriocarcinoma↗
PubMed1988

Trophoblastic embolism in sudden maternal death.

Trophoblastic embolism (TE) was shown in three out of eight maternal autopsy cases. The trophoblasts of TE were easily identified by the immunocytochemical method with antisera to placental antigen (PA) and human placental lactogen (HPL). Two types of TE were differentiated in the morphology of trophoblasts: One was formed of whole trophoblastic cells (TE-Type I) and the other was composed of amorphous trophoblastic fragments (TE-Type II). The TE-Type II was confirmed in the central nervous system (trophoblastic emboli in brain) and appeared to be the sudden maternal death cause.

Adult↗
PubMed1987

Differentiation molecules of the equine trophoblast.

Monoclonal antibodies raised against horse placenta were tested using an indirect immunoperoxidase-labelling technique for reactivity with a panel of tissues from adult horses and conceptuses of various gestational ages. The pattern of reactivity of 4 of the antibodies (F67.1, F71.3, F71.7, F71.14) on trophoblastic tissues described unique antigenic phenotypes for the non-invasive trophoblast of the allantochorion, the invasive trophoblast of the chorionic girdle, and the mature endometrial cup cells, which are derived from the chorionic girdle. Two of the monoclonal antibodies (F67.1 and F71.3) reacted only with chorionic girdle and the endometrial cups. Antibody F71.7 labelled strongly the non-invasive allantochorion from Day 29 of gestation to term. However, F71.7 failed to label mature endometrial cups and stained chorionic girdle only weakly, suggesting that the ability of the girdle cells to synthesize the molecule identified by F71.7 was gradually lost after development of the girdle. Antibody F71.14 reacted with trophoblastic tissues from all stages of gestation tested, with the exception of chorionic girdle. The other 3 anti-trophoblast monoclonal antibodies (F71.1, F71.2 and F71.8) labelled trophoblast-derived tissues from all stages tested. When the monoclonal antibodies were tested on cultured fetal and placental cells from Day 33 conceptuses recovered non-surgically from pregnant mares, the reactivities of the monoclonal antibodies on cultured cells were mostly identical to their reactivities in situ on tissue samples of similar gestational age; F67.1 and F71.3 were strong, specific markers for chorionic girdle cells, and F71.7 labelled allantochorion weakly in vitro, but failed to label chorionic girdle cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

[Studies on the interaction between trophoblastic invasion and maternal immune cell infiltration at the implantation site in early human pregnancy by means of double immunoperoxidase technic using monoclonal antibodies].

Interaction between trophoblastic invasion and maternal immune cell infiltration at the implantation sites in early human pregnancy was analyzed by means of a double immunoperoxidase technique using Troma-1, a rat monoclonal antibody, which recognizes trophoblastic cells and a set of mouse monoclonal antibodies to react with various immune cells. The results were as follows. The most prominent immune cells in the implantation sites were monocytes/macrophages, which were positive for HLA-DR. These cells were adjacent to trophoblastic cells which were infiltrating into the decidua basalis. It therefore appeared that these cells function as "antigen presenting cells" which recognize and present the processed fetal information to maternal T cells. A small number of cells with mature T cell markers were found to be infiltrating around the anchoring villi and the extra-villous trophoblastic cells in the decidua compacta. But a larger number of T cells were adjacent to the villi in the decidua spongiosa and the extra-villous trophoblastic cells invading the decidua spongiosa and the myometrium. These cells may therefore play a role in preventing trophoblastic cells from invading the myometrium in the implantation sites. A relatively large number of cells with E rosette receptors but without mature T cell markers were observed in the decidua basalis, but few were found in the myometrium, into which a larger number of mature T cells were infiltrating. The distribution of particular cells was similar to that of endometrial granulocytes studied in our laboratory. There were thus likely to be immune cells in humans equivalent to non-T granulated suppressor cells in mice, which have been shown to suppress the generation of cytotoxic T cells (Clark et al.).

Antibodies, Monoclonal↗
PubMed1981

Endocrine aspects of trophoblastic neoplasia.

The trophoblastic cells in both benign and malignant trophoblastic disease secrete a variety of steroid, polypeptide and hormonal agents. Those substances that are known to be elaborated by the neoplastic trophoblastic tissue include hCG, a substance with TSH-like activity, estrogens, progestogens and placental lactogen. The most well characterized of these is hCG, which can be assayed easily. The level of hCG plays an important role in the diagnosis, management and follow-up of patients with trophoblastic disease. Because of this, a sensitive assay that does not cross-react with LH would be ideal. It appears that some of the clinical signs and symptoms seen in these patients (including toxemia, theca lutein cyst, hyperthyroidism and thyrotoxicosis, and galactorrhea) are a direct manifestation or reflection of the level of hCG. There is very little information available at this time on the pathophysiologic role that hCG plays at the cellular level in causing these signs and symptoms. Many questions remain to be answered regarding the role of the other hormones in trophoblastic disease and how they affect the patient. Additionally, very little is known about the potential use of the other hormones in diagnosis, management and follow-up of patients with trophoblastic disease.

Chorionic Gonadotropin↗
PubMed1981

Human extra-embryonic membranes: role of trophoblast in normal and abnormal pregnancies.

The human embryo is encased in extra-embryonic membranes which are covered with trophoblast throughout pregnancy. Bits and pieces of trophoblast break away from the placenta and are swept into the mother's circulation to lodge in her lungs without causing evidence of inflammation or rejection. This is in part due to an absence of histocompatibility antigens from trophoblast membranes, but it may also be due to a structural glycoprotein which is capable of inhibiting allogeneic recognition and rejection reactions. Another glycoprotein of the trophoblast is shared with lymphocytes, and serological studies have shown this to be polymorphic. Evidence has also been accumulated that this genetically determined cell membrane component is associated with the major histocompatibility complex, and that maternal recognition of this may be necessary to produce blocking factors that protect trophoblast from maternal rejection. Women who lack these factors during pregnancy tend to abort, and some of these patients also share several HLA antigens with their husbands. In an effort to produce blocking factors artificially, four aborting women were immunized with trophoblast-lymphocyte cross-reactive antigens, and this has resulted in normal pregnancies and the delivery of healthy babies at term. This finding suggests that genetical diversity of HLA is associated with TLX antigens, thus providing a mechanism whereby HLA not only generates but is also responsible for the perpetuation of diversity in human populations.

Abortion, Spontaneous↗
PubMed1981

An immune dependency of trophoblastic growth implied by the antithetic difference in immunology between spontaneous abortion and hydatidiform mole.

It may be difficult to demonstrate clearly an immune dependency of trophoblast growth in vivo. The author's standpoint, however, is that comparative study of the immunology of SpA and HM must attempt to demonstrate it. In this chapter, before entering the main topics, the genesis of HM in relation to early SpA, the dependency of trophoblastic cell growth on the presence of an embryo or fetus, as evidenced by animal experiments, and the pathology and cytogenetics of SpA were outlined in a summarized form. This summary was provided to stress that the comparative immunologic study of SpA and HM may be a very useful experimental model in the elucidation of an immune dependency of trophoblastic cell growth in vivo. Many immunologically antithetic differences between SpA and HM were found and the important role that BA plays in trophoblastic cell growth was strongly suggested by the considerations of immune injury to the trophoblast in SpA and of the immune survival of the trophoblast in HM. Thus, we have come to believe that our clinical and experimental model described here might illustrate a new aspect of reproductive immunology, while contributing to the elucidation of SpA and HM genesis. Further studies along these lines may be useful and, needless to say, should be performed.

Abortion, Spontaneous↗