Biomedical subjects

Caryn Greenfield

Publications and source records attributed to Caryn Greenfield.

5 recordsLinked to original sources

PubMed2006

Decidual NK cells regulate key developmental processes at the human fetal-maternal interface.

Human CD56(bright) NK cells accumulate in the maternal decidua during pregnancy and are found in direct contact with fetal trophoblasts. Several mechanisms have been proposed to explain the inability of NK cells to kill the semiallogeneic fetal cells. However, the actual functions of decidual NK (dNK) cells during pregnancy are mostly unknown. Here we show that dNK cells, but not peripheral blood-derived NK subsets, regulate trophoblast invasion both in vitro and in vivo by production of the interleukin-8 and interferon-inducible protein-10 chemokines. Furthermore, dNK cells are potent secretors of an array of angiogenic factors and induce vascular growth in the decidua. Notably, such functions are regulated by specific interactions between dNK-activating and dNK-inhibitory receptors and their ligands, uniquely expressed at the fetal-maternal interface. The overall results support a 'peaceful' model for reproductive immunology, in which elements of innate immunity have been incorporated in a constructive manner to support reproductive tissue development.

Angiogenesis Inducing Agents↗

PubMed2005

Expression and regulation of Sprouty-2 in the granulosa-lutein cells of the corpus luteum.

Growth factor signalling has important modulatory roles in the process of human follicular growth, oocyte maturation and corpus luteum (CL) formation. Recently, Sprouty-2, an inhibitor of receptor tyrosine kinase (RTK) signalling pathway was advocated as a marker of oocyte competence in the bovine ovary. We sought to study Sprouty-2 expression and regulation in the human ovary. RT-PCR was used to detect Sprouty-2 mRNA in human granulosa-lutein cells (GLC) collected from follicular aspiration of IVF patients. The effect of epidermal and fibroblast growth factors (EGF and FGF) on Sprouty-2 mRNA expression in GLC was studied using quantitative real-time PCR. Immunohistochemistry was performed on cultured GLC, human CL and stimulated rat ovary sections. Sprouty-2 mRNA was expressed in human GLC. EGF and basic FGF, but not FGF4 and FGF10, increased Sprouty-2 mRNA expression in GLC. The Sprouty protein was localized to GLC of early and late human CL but not to the theca cell layer. Immunostaining of developing rat CL confirmed the temporal and spatial expression of Sprouty in humans. The detection of Sprouty-2 mRNA and protein in human GLC may suggest a role for Sprouty-2 during the final stages of follicle maturation and CL formation.

Adolescent↗

PubMed2005

Fibroblast growth factor-10 and fibroblast growth factor receptors 1-4: expression and peptide localization in human decidua and placenta.

The development of the chorionic villous tree into a complex and organized ramified tubular network can be termed branching morphogenesis. Studying the molecular mechanisms involved in this process may contribute to the understanding of pregnancy complications such as preeclampsia. We hypothesized that fibroblast growth factor-10 (FGF-10) and fibroblast growth factor receptors 1-4 (FGFR 1-4) are expressed in human decidual and placental tissues. We analyzed the expression of FGF-10 and FGFRs 1-4 in 1st, 2nd and 3rd trimester placentas, as well as in decidua. RT-PCR and immunohistochemistry were employed to study mRNA and protein expression. FGF-10 was expressed by decidual cells and by cytotrophoblasts of the cytotrophoblast columns during all three trimesters. FGFR 1-4 were expressed in the placenta but not in the decidua. Placental expression of FGFRs was temporally regulated: In 1st trimester placentas, FGFR 1-4 were expressed by Hofbauer cells, FGFR-1 and FGFR-4 were expressed in cytotrophoblast columns, and the latter was also expressed by syncytiotrophoblasts. Similar expression was seen in 2nd trimester placentas with additional expression of FGFR-1 in blood vessel walls. The expression of FGFR-1 and FGFR-4 in the 3rd trimester was comparable to that seen in the 2nd trimester. The expression of FGF-10, FGFR-1 and FGFR-4 in the maternal-fetal interphase suggests their role in decidual-trophoblast interaction. The abundance of FGFR expression in Hofbauer cells implies that mesenchymal-trophoblast interaction is important for regulation of villous development.

Decidua↗

PubMed2005

Spatiotemporal expression of heparanase during human and rodent ovarian folliculogenesis.

Heparanase (HPSE) is an endoglycosidase that cleaves heparan sulfate proteoglycans (HSPGs), major components of the basement membrane (BM) and extracellular matrix (ECM). Heparanase activity results in release of HSPG-bound molecules, including basic fibroblast growth factor (FGF2). Structural and functional development of the corpus luteum (CL) involves tissue remodeling, active angiogenesis, and steroid production. Heparanase-induced ECM and BM breakdown as well as FGF2-stimulated endothelial proliferation may have an important role in the regulation of luteal function. Heparanase mRNA was detected by reverse-transcription-polymerase chain reaction in granulosa cells recovered from follicular fluid of in vitro fertilization patients. Using sulfate-labeled ECM, heparanase enzymatic activity was determined in human luteinized granulosa cells. Employing immunohistochemistry, heparanase protein was localized predominantly in the theca interna cell layer of the mature antral follicle, whereas in human corpora lutea, both luteinized granulosa and theca cells were immunostained for heparanase. During luteolysis, heparanase was identified in macrophages surrounding the forming corpus albicans. In serially sectioned ovaries from unstimulated rats as well as from eCG-treated rats, expression of heparanase was noted exclusively in the ovarian steroid-producing interstitial tissue. Following an ovulatory dose of hCG, heparanase was immunostained also in lutein cells of the forming corpora lutea. Temporal expression of heparanase in granulosa cells during the luteal phase and in macrophages during luteal regression supports the hypothesis that heparanase plays a role in human ovarian ECM remodeling and may potentiate cellular migration and growth factor bioavailability.

Adolescent↗

PubMed2002

Localization of heparanase in normal and pathological human placenta.

Degradation of extracellular matrix (ECM) components is critical for invasion. Heparan sulphate proteoglycans are abundant in the ECM of the placenta and the decidua, hence their degradation may disassemble the matrix and facilitate placentation and trophoblast invasion. This study investigates the expression of heparanase in normal and pathological placentation using RT-PCR, in-situ hybridization and immunohistochemistry analysis to detect heparanase in specific cells of the placenta and at the fetal-maternal interface throughout pregnancy. Heparanase was observed in villous cytotrophoblasts (CT), syncytial trophoblasts (ST) and in intermediate trophoblast cell columns in normal first trimester, molar and ectopic pregnancies. The heparanase protein was preferentially expressed in the endothelium of fetal capillaries, and to a much lesser extent in larger fetal vessels. Extravillous trophoblasts (EVT) invading the decidua and the maternal vessels were also heparanase positive. In the second and third trimesters, villous CT remained heparanase positive whereas ST showed variable heparanase expression. EVT invading the placental implantation site were also positively stained. A similar pattern was observed in samples obtained from pre-eclamptic placentae and from placenta accreta. Our results indicate consistent expression of heparanase in normal and abnormal placenta, in small fetal vessels and in a variety of trophoblast subpopulations with different invasive potentials.

Female↗