Trophoblasts: Cells lining the outside of the BLASTOCYST. After binding to the ENDOMETRIUM, trophoblasts develop into two distinct layers, an inner layer of mononuclear cytotrophoblasts and an outer layer of continuous multinuclear cytoplasm, the syncytiotrophoblasts, which form the early fetal-maternal interface (PLACENTA).Placenta: A highly vascularized mammalian fetal-maternal organ and major site of transport of oxygen, nutrients, and fetal waste products. It includes a fetal portion (CHORIONIC VILLI) derived from TROPHOBLASTS and a maternal portion (DECIDUA) derived from the uterine ENDOMETRIUM. The placenta produces an array of steroid, protein and peptide hormones (PLACENTAL HORMONES).Placentation: The development of the PLACENTA, a highly vascularized mammalian fetal-maternal organ and major site of transport of oxygen, nutrients, and fetal waste products between mother and FETUS. The process begins at FERTILIZATION, through the development of CYTOTROPHOBLASTS and SYNCYTIOTROPHOBLASTS, the formation of CHORIONIC VILLI, to the progressive increase in BLOOD VESSELS to support the growing fetus.Pregnancy: The status during which female mammals carry their developing young (EMBRYOS or FETUSES) in utero before birth, beginning from FERTILIZATION to BIRTH.Chorionic Villi: The threadlike, vascular projections of the chorion. Chorionic villi may be free or embedded within the DECIDUA forming the site for exchange of substances between fetal and maternal blood (PLACENTA).Choriocarcinoma: A malignant metastatic form of trophoblastic tumors. Unlike the HYDATIDIFORM MOLE, choriocarcinoma contains no CHORIONIC VILLI but rather sheets of undifferentiated cytotrophoblasts and syncytiotrophoblasts (TROPHOBLASTS). It is characterized by the large amounts of CHORIONIC GONADOTROPIN produced. Tissue origins can be determined by DNA analyses: placental (fetal) origin or non-placental origin (CHORIOCARCINOMA, NON-GESTATIONAL).Pregnancy Trimester, First: The beginning third of a human PREGNANCY, from the first day of the last normal menstrual period (MENSTRUATION) through the completion of 14 weeks (98 days) of gestation.Decidua: The hormone-responsive glandular layer of ENDOMETRIUM that sloughs off at each menstrual flow (decidua menstrualis) or at the termination of pregnancy. During pregnancy, the thickest part of the decidua forms the maternal portion of the PLACENTA, thus named decidua placentalis. The thin portion of the decidua covering the rest of the embryo is the decidua capsularis.Embryo Implantation: Endometrial implantation of EMBRYO, MAMMALIAN at the BLASTOCYST stage.Pregnancy Proteins: Proteins produced by organs of the mother or the PLACENTA during PREGNANCY. These proteins may be pregnancy-specific (present only during pregnancy) or pregnancy-associated (present during pregnancy or under other conditions such as hormone therapy or certain malignancies.)HLA-G Antigens: Class I human histocompatibility (HLA) surface antigens encoded by alleles on locus B of the HLA complex. The HLA-G antigens are considered non-classical class I antigens due to their distinct tissue distribution which differs from HLA-A; HLA-B; and HLA-C antigens. Note that several isoforms of HLA-G antigens result from alternative splicing of messenger RNAs produced from the HLA-G*01 allele.Pre-Eclampsia: A complication of PREGNANCY, characterized by a complex of symptoms including maternal HYPERTENSION and PROTEINURIA with or without pathological EDEMA. Symptoms may range between mild and severe. Pre-eclampsia usually occurs after the 20th week of gestation, but may develop before this time in the presence of trophoblastic disease.Placenta Diseases: Pathological processes or abnormal functions of the PLACENTA.Giant Cells: Multinucleated masses produced by the fusion of many cells; often associated with viral infections. In AIDS, they are induced when the envelope glycoprotein of the HIV virus binds to the CD4 antigen of uninfected neighboring T4 cells. The resulting syncytium leads to cell death and thus may account for the cytopathic effect of the virus.Blastocyst: A post-MORULA preimplantation mammalian embryo that develops from a 32-cell stage into a fluid-filled hollow ball of over a hundred cells. A blastocyst has two distinctive tissues. The outer layer of trophoblasts gives rise to extra-embryonic tissues. The inner cell mass gives rise to the embryonic disc and eventual embryo proper.Chorion: The outermost extra-embryonic membrane surrounding the developing embryo. In REPTILES and BIRDS, it adheres to the shell and allows exchange of gases between the egg and its environment. In MAMMALS, the chorion evolves into the fetal contribution of the PLACENTA.Maternal-Fetal Exchange: Exchange of substances between the maternal blood and the fetal blood at the PLACENTA via PLACENTAL CIRCULATION. The placental barrier excludes microbial or viral transmission.Placental Lactogen: A polypeptide hormone of approximately 25 kDa that is produced by the SYNCYTIOTROPHOBLASTS of the PLACENTA, also known as chorionic somatomammotropin. It has both GROWTH HORMONE and PROLACTIN activities on growth, lactation, and luteal steroid production. In women, placental lactogen secretion begins soon after implantation and increases to 1 g or more a day in late pregnancy. Placental lactogen is also an insulin antagonist.Uterus: The hollow thick-walled muscular organ in the female PELVIS. It consists of the fundus (the body) which is the site of EMBRYO IMPLANTATION and FETAL DEVELOPMENT. Beyond the isthmus at the perineal end of fundus, is CERVIX UTERI (the neck) opening into VAGINA. Beyond the isthmi at the upper abdominal end of fundus, are the FALLOPIAN TUBES.Endometrium: The mucous membrane lining of the uterine cavity that is hormonally responsive during the MENSTRUAL CYCLE and PREGNANCY. The endometrium undergoes cyclic changes that characterize MENSTRUATION. After successful FERTILIZATION, it serves to sustain the developing embryo.Cells, Cultured: Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.Chorionic Gonadotropin: A gonadotropic glycoprotein hormone produced primarily by the PLACENTA. Similar to the pituitary LUTEINIZING HORMONE in structure and function, chorionic gonadotropin is involved in maintaining the CORPUS LUTEUM during pregnancy. CG consists of two noncovalently linked subunits, alpha and beta. Within a species, the alpha subunit is virtually identical to the alpha subunits of the three pituitary glycoprotein hormones (TSH, LH, and FSH), but the beta subunit is unique and confers its biological specificity (CHORIONIC GONADOTROPIN, BETA SUBUNIT, HUMAN).Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.Pregnancy, Animal: The process of bearing developing young (EMBRYOS or FETUSES) in utero in non-human mammals, beginning from FERTILIZATION to BIRTH.Uterine Neoplasms: Tumors or cancer of the UTERUS.Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents.Gestational Age: The age of the conceptus, beginning from the time of FERTILIZATION. In clinical obstetrics, the gestational age is often estimated as the time from the last day of the last MENSTRUATION which is about 2 weeks before OVULATION and fertilization.Placental Circulation: The circulation of BLOOD, of both the mother and the FETUS, through the PLACENTA.Pregnancy Trimester, Third: The last third of a human PREGNANCY, from the beginning of the 29th through the 42nd completed week (197 to 294 days) of gestation.Fibroblast Growth Factor 4: A HEPARIN binding fibroblast growth factor that may play a role in LIMB BUDS development.Hydatidiform Mole: Trophoblastic hyperplasia associated with normal gestation, or molar pregnancy. It is characterized by the swelling of the CHORIONIC VILLI and elevated human CHORIONIC GONADOTROPIN. Hydatidiform moles or molar pregnancy may be categorized as complete or partial based on their gross morphology, histopathology, and karyotype.RNA, Messenger: RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.Cell Line: Established cell cultures that have the potential to propagate indefinitely.Gene Expression Regulation, Developmental: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action during the developmental stages of an organism.Keratin-7: A type II keratin found associated with KERATIN-19 in ductal epithelia and gastrointestinal epithelia.Trophoblastic Neoplasms: Trophoblastic growth, which may be gestational or nongestational in origin. Trophoblastic neoplasia resulting from pregnancy is often described as gestational trophoblastic disease to distinguish it from germ cell tumors which frequently show trophoblastic elements, and from the trophoblastic differentiation which sometimes occurs in a wide variety of epithelial cancers. Gestational trophoblastic growth has several forms, including HYDATIDIFORM MOLE and CHORIOCARCINOMA. (From Holland et al., Cancer Medicine, 3d ed, p1691)Cell Movement: The movement of cells from one location to another. Distinguish from CYTOKINESIS which is the process of dividing the CYTOPLASM of a cell.Fetal Growth Retardation: The failure of a FETUS to attain its expected FETAL GROWTH at any GESTATIONAL AGE.Embryo, Mammalian: The entity of a developing mammal (MAMMALS), generally from the cleavage of a ZYGOTE to the end of embryonic differentiation of basic structures. For the human embryo, this represents the first two months of intrauterine development preceding the stages of the FETUS.Embryonic Development: Morphological and physiological development of EMBRYOS.Reverse Transcriptase Polymerase Chain Reaction: A variation of the PCR technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard PCR protocols.Pregnancy, Tubal: The most common (>96%) type of ectopic pregnancy in which the extrauterine EMBRYO IMPLANTATION occurs in the FALLOPIAN TUBE, usually in the ampullary region where FERTILIZATION takes place.Extraembryonic Membranes: The thin layers of tissue that surround the developing embryo. There are four extra-embryonic membranes commonly found in VERTEBRATES, such as REPTILES; BIRDS; and MAMMALS. They are the YOLK SAC, the ALLANTOIS, the AMNION, and the CHORION. These membranes provide protection and means to transport nutrients and wastes.Trophoblastic Tumor, Placental Site: An uncommon variant of CHORIOCARCINOMA. It is composed almost entirely of mononuclear cytotrophoblasts (TROPHOBLASTS). Because its secretion of hCG (CHORIONIC GONADOTROPIN) is low, a large tumor may develop before the hCG can be detected.Embryo Loss: Early pregnancy loss during the EMBRYO, MAMMALIAN stage of development. In the human, this period comprises the second through eighth week after fertilization.Encyclopedias as Topic: Works containing information articles on subjects in every field of knowledge, usually arranged in alphabetical order, or a similar work limited to a special field or subject. (From The ALA Glossary of Library and Information Science, 1983)Hepatitis, Infectious Canine: A contagious disease caused by canine adenovirus (ADENOVIRUSES, CANINE) infecting the LIVER, the EYE, the KIDNEY, and other organs in dogs, other canids, and bears. Symptoms include FEVER; EDEMA; VOMITING; and DIARRHEA.Dog Diseases: Diseases of the domestic dog (Canis familiaris). This term does not include diseases of wild dogs, WOLVES; FOXES; and other Canidae for which the heading CARNIVORA is used.L-Selectin: Cell adhesion molecule and CD antigen that serves as a homing receptor for lymphocytes to lymph node high endothelial venules.

Mrj encodes a DnaJ-related co-chaperone that is essential for murine placental development. (1/2449)

We have identified a novel gene in a gene trap screen that encodes a protein related to the DnaJ co-chaperone in E. coli. The gene, named Mrj (mammalian relative of DnaJ) was expressed throughout development in both the embryo and placenta. Within the placenta, expression was particularly high in trophoblast giant cells but moderate levels were also observed in trophoblast cells of the chorion at embryonic day 8.5, and later in the labyrinth which arises from the attachment of the chorion to the allantois (a process called chorioallantoic fusion). Insertion of the ROSAbetageo gene trap vector into the Mrj gene created a null allele. Homozygous Mrj mutants died at mid-gestation due to a failure of chorioallantoic fusion at embryonic day 8.5, which precluded formation of the mature placenta. At embryonic day 8.5, the chorion in mutants was morphologically normal and expressed the cell adhesion molecule beta4 integrin that is known to be required for chorioallantoic fusion. However, expression of the chorionic trophoblast-specific transcription factor genes Err2 and Gcm1 was significantly reduced. The mutants showed no abnormal phenotypes in other trophoblast cell types or in the embryo proper. This study indicates a previously unsuspected role for chaperone proteins in placental development and represents the first genetic analysis of DnaJ-related protein function in higher eukaryotes. Based on a survey of EST databases representing different mouse tissues and embryonic stages, there are 40 or more DnaJ-related genes in mammals. In addition to Mrj, at least two of these genes are also expressed in the developing mouse placenta. The specificity of the developmental defect in Mrj mutants suggests that each of these genes may have unique tissue and cellular activities.  (+info)

An ultrastructural study of implantation in the golden hamster. II. Trophoblastic invasion and removal of the uterine epithelium. (2/2449)

Sixty six implantation sites from 18 golden hamsters were examined with light and electron microscopy between 4 and 5 1/2 days of pregnancy (post-ovulation). At 4 days some blastocysts began to invade the uterine epithelium, with trophoblastic processes penetrating and engulfing portions of the uterine epithelium. The majority of epithelial cells appeared normal before invasion, although at two implantation sites three or four adjoining epithelial cells were necrotic before penetration by the trophoblast. In general the epithelial cells were degenerating at the time the trophoblast invaded the epithelium. Inclusions, representing portions of the engulfed epithelium, and varying in size and electron density, were present throughout the invading trophoblast cells at 4 1/2 and 5 days of pregnancy. At 5 1/2 days the uterine epithelium had disappeared and the embryo was now almost completely surrounded by blood lacunae.  (+info)

Expression of trophinin, tastin, and bystin by trophoblast and endometrial cells in human placenta. (3/2449)

Trophinin, tastin, and bystin comprise a complex mediating a unique homophilic cell adhesion between trophoblast and endometrial epithelial cells at their respective apical cell surfaces. In this study, we prepared mouse monoclonal antibodies specific to each of these molecules. The expression of these molecules in the human placenta was examined immunohistochemically using the antibodies. In placenta from the 6th week of pregnancy, trophinin and bystin were found in the cytoplasm of the syncytiotrophoblast in the chorionic villi, and in endometrial decidual cells at the utero placental interface. Tastin was exclusively present on the apical side of the syncytiotrophoblast. Tissue sections were also examined by in situ hybridization using RNA probes specific to each of these molecules. This analysis showed that trophoblast and endometrial epithelial cells at the utero placental interface express trophinin, tastin, and bystin. In wk 10 placenta, trophinin and bystin were found in the intravillous cytotrophoblast, while tastin was not found in the villi. After wk 10, levels of all three proteins decreased and then disappeared from placental villi.  (+info)

Human uterine lymphocytes. (4/2449)

During the luteal phase and the early months of pregnancy, there is a dense mucosal infiltration of CD56+ natural killer (NK) cells. These uterine NK cells have a phenotype (CD56bright, CD16-, mCD3-) which distinguishes them from peripheral blood NK cells (CD56dim, CD16bright, mCD3-). The uterine NK cells are in close association with extravillous trophoblast (EVT) cells which infiltrate into the decidua and maternal spiral arteries. This subpopulation of trophoblast expresses two human leukocyte antigen (HLA) class I molecules, HLA-G and HLA-C. Circulating NK cells express receptors for HLA class I molecules. We have recently found evidence that similar receptors are present on decidual NK cells belonging to both the Killer Inhibitory Receptor (KIR) and CD94 families. The repertoire of NK receptors expressed varies between different women. The findings indicate that decidual NK cells do have receptors for trophoblast HLA class I molecules. Experiments are underway to determine the effects of this interaction on NK cell function.  (+info)

The CTLA-4 gene is expressed in placental fibroblasts. (5/2449)

In order to elucidate the mechanisms that ensure survival of the allogeneic fetus, we are investigating the expression pattern of genes that are involved in peripheral self-tolerance in tissues at the maternal-fetal interface. Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) is a negative regulator of T cell activation and may modulate peripheral self-tolerance. Previously, we reported the preferential transmission of maternally-inherited shorter alleles at a 3'-UTR microsatellite locus to liveborn children, but random transmission of paternally-inherited alleles, suggesting that CTLA-4 may be involved in the maintenance of tolerance at the maternal-fetal interface. In this report, we demonstrate that CTLA-4 mRNA and protein are indeed expressed in fetal tissues at the maternal-fetal interface throughout gestation.  (+info)

Role of proteases in implantation. (6/2449)

Implantation of the embryo into the endometrium is a critical step in the establishment of pregnancy and the failure of embryos to implant is a major limiting factor in the success of reproductive technologies. Furthermore, one or more of the molecules of importance at implantation could provide a suitable target for post-coital contraception. While there is considerable species variation in the extent to which the trophoblast invades the maternal endometrium and makes contact with the maternal blood supply, many of the molecular mechanisms are conserved among species. Three families of protease are involved in the matrix degradation required for implantation: the cysteine, serine and matrix metalloproteinases. Other proteases are required for the activation of regulatory molecules. Although trophoblast from all species appears to have a high invasive potential, this is limited by the presence of partner protease inhibitors, the presence of which provides restraint to this invasion. It is the balance between the proteases and their inhibitors at any focal point that determines the site and extent of trophoblast invasion. This review examines the literature regarding proteases and their inhibitors at early implantation sites across a range of species with very different forms of placentation and evaluates their common features and their dissimilarities.  (+info)

CD9 is expressed in extravillous trophoblasts in association with integrin alpha3 and integrin alpha5. (7/2449)

The CD9 molecule is a 24-27 kDa cell surface glycoprotein, which may be related to Schwann cell migration and adhesion. In this study, we examined the expression of CD9 in human extravillous trophoblasts, which invade into the endometrium during implantation and placentation. CD9 was detected immunohistochemically on the extravillous trophoblasts in the cell columns of first trimester placentae, but not on villous trophoblasts. In the second and third trimester, CD9 was highly expressed on the extravillous trophoblasts in the basal plate of placentae, and in the chorion laeve in the fetal membrane of term placentae. The molecular mass of CD9 in the chorion laeve was shown to be 27 kDa by Western blotting. The mRNA of CD9 was also detected in the chorion laeve by reverse transcription-polymerase chain reaction (RT-PCR). Proteins were purified from chorion laeve by affinity chromatography with anti-integrin alpha3 and alpha5 monoclonal antibodies and Western blotting, revealed that CD9 was associated with both integrins. These findings indicate that CD9 is a differentiation-related molecule present in the extravillous trophoblasts. Since it is associated with integrin alpha5 which has been proposed to regulate trophoblast invasion, CD9 may be implicated in trophoblast invasion at the feto-maternal interface.  (+info)

CD9 is involved in invasion of human trophoblast-like choriocarcinoma cell line, BeWo cells. (8/2449)

The CD9 molecule is expressed on human extravillous trophoblasts, which invade the endometrium during implantation and placentation. To elucidate the role of CD9 in trophoblastic function, we investigated the expression of CD9 protein and mRNA in BeWo cells, a human trophoblast-like choriocarcinoma cell line, using immunohistochemistry, Western blotting and reverse transcription-polymerase chain reaction (RT-PCR). When BeWo cells were cultured with anti-CD9 monoclonal antibodies (mAb), their invasion through the extracellular matrices was significantly enhanced in a dose-dependent manner. Cell proliferation and human chorionic gonadotrophin production were unaffected. On the other hand, culture in the presence of mAb against integrins alpha3, alpha5 and beta1, which partially block the interaction with the extracellular matrices, inhibited BeWo cell invasion. Anti-CD9 monoclonal antibody had a stimulatory effect on BeWo cell invasion in the presence of anti-integrin alpha3 antibody. In contrast, it had no effect in the presence of mAb against integrins alpha5 and beta1, which were also highly expressed on BeWo cells. These findings suggest that CD9 has a function connected with the invasive properties of BeWo cells, which is partially mediated by integrin alpha5beta1. This may relate to the involvement of CD9 in trophoblastic invasion.  (+info)

  • Additional assays performed in the presence of neutralizing anti-IL-10 antibodies and exogenous IL-10 demonstrate that reduced macrophage cytotoxicity and proliferation, but increased cell motility result from the ability of trophoblast IL-10 to sustain Stat3 activation and suppress IFN-γ-induced Stat1 activation. (
  • Overexpression of TPα enhanced trophoblast proliferation and syncytialisation. (
  • Our recent studies demonstrated that responses of both human and mouse trophoblast cells to IFN-gamma are significantly reduced relative to other cell types, which correspond with both the inability to express MHC class II molecules, and resistance of trophoblast cells to IFN-gamma-mediated apoptosis and inhibition of cell proliferation. (
  • In developed nations the most common cause of IUGR is impaired placentation resulting from poor trophoblast function, which reduces blood flow to the fetoplacental unit, promotes hypoxia and enhances production of bioactive lipids (TXA2 and isoprostanes) which act through the thromboxane receptor (TP). (
  • 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. (
  • 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. (
  • however, up-regulation of non-trophoblast genes suggests a somewhat diverse response to BMP4/FGF-2. (
  • We previously demonstrated that the inability of human and rodent trophoblast cells to transcribe MHC class II genes following IFN-gamma treatment results from silencing of expression of the class II transactivator (CIITA), a transacting transcription factor essential for constitutive and IFN-gamma-inducible transcription in other cell types. (
  • Loke YW, Whyte A, Davie P: Differential expression of trophoblast-specific membrane antigens by normal and abnormal human placentae and by neoplasms of trophoblastic and non-trophoblastic origin. (
  • 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. (
  • Thus, successful reproduction of mammals may require that MHC class II gene expression be stringently repressed in trophoblast cells. (
  • Our studies to date suggest that silencing of CIITA expression in trophoblast cells exposed to IFN-gamma is due to at least two overlapping mechanisms: 1) hyporesponsiveness to IFN-gamma, and 2) a repressive chromatin structure at the CIITA promoter. (
  • Trophoblasts (from Greek trephein: to feed, and blastos: germinator) are cells forming the outer layer of a blastocyst, which provide nutrients to the embryo and develop into a large part of the placenta. (