Biomedical subjects

Donald S Torry

Publications and source records attributed to Donald S Torry.

5 recordsLinked to original sources

PubMed2006

Correlations of placental perfusion and PlGF protein expression in early human pregnancy.

OBJECTIVE: The purpose of this study was to investigate temporal correlations between maternal serum placenta growth factor levels and placental perfusion in early human pregnancies. STUDY DESIGN: Systolic umbilical artery Doppler blood flow velocity indices at fetal and placental insertion sites were measured between 7 and 22 weeks of gestation from normal singleton pregnancies. Maternal serum placenta growth factor levels were determined by enzyme-linked immunosorbent assay. RESULTS: Maternal serum placenta growth factor levels showed an exponential increase at approximately 14 weeks of gestation. Placenta perfusion, as estimated by systolic Doppler blood flow indices, significantly increased with gestational age (P < .0001). There was a close association between placenta growth factor expression levels and evidence of increased placenta perfusion (P < .033). CONCLUSION: The significant increase in serum placenta growth factor coincides with the increased perfusion of the maternal/fetal interface at approximately 12 to 14 weeks of gestation. Correlation of placenta growth factor expression and placental perfusion suggests that placenta growth factor may contribute to assuring adequate vascular development/function of the placenta early in gestation.

Adult↗

PubMed2005

The immunomodulatory proteins B7-DC, B7-H2, and B7-H3 are differentially expressed across gestation in the human placenta.

Placental trophoblast cells form a cellular barrier between the potentially immunogenic fetus and maternal leukocytes. Trophoblasts subvert maternal immunity by producing surface-bound and soluble factors that interact with maternal leukocytes. Here, we describe the distribution of three members of the expanding family of B7 immunomodulatory molecules: B7-DC, B7-H2, and B7-H3. B7-DC and B7-H3 inhibit antigen-stimulated lymphocyte activation while B7-H2 serves in a regulatory capacity, often promoting a Th2 immunophenotype. First trimester and term placentas, purified trophoblast cells, choriocarcinoma cell lines, and human umbilical vein endothelial cells were analyzed for B7 family RNA and protein expression. Transcripts and proteins for all three B7s were present throughout gestation but were differentially expressed within the trophoblast and the stroma. Whereas B7-DC was prominent on the syncytiotrophoblast of early placenta, it was absent from the trophoblast at term. In contrast, B7-H2 and B7-H3 were prominent on the extravillous trophoblast throughout gestation. Lastly, stromal cells, including macrophages and endothelial cells, differentially expressed B7-DC, B7-H2, and B7-H3, depending on gestational age. Thus, all three of these newly discovered B7 proteins are differentially positioned at the maternal-fetal interface such that they could steer maternal leukocytes away from a harmful immune response and toward a favorable one.

Antigens, CD↗

PubMed2004

Determinants of placental vascularity.

PROBLEM: Vascular growth during implantation and placentation is critical for successful gestation and it is thought that vascular insufficiencies during placentation contribute to a number of obstetrical complications. However, relatively little is known regarding the regulation of angiogenesis in the placenta. METHOD OF STUDY: We review literature concerning the potential significance of inadequate placental vascularity as a contributor to the obstetrical complications of spontaneous abortion, fetal growth restriction and preeclampsia. Gene expression assays were used to compare fluctuations of placenta growth factor (PlGF) and PlGF receptor expression in normal and preeclamptic trophoblast in vitro. RESULTS: Studies have shown that common obstetrical complications manifest altered placental vascularity. Both intrinsic defects (gene knockouts) and extrinsic factors (O(2) tension, cytokines, etc) may be responsible for the defects. Some of these factors have been shown to influence trophoblast vascular endothelial growth factor (VEGF)/PlGF expression suggesting this particular family of angiogenic proteins play an important role in placental angiogenesis. CONCLUSION: Placental vascularization reflects a complex interaction of regulatory factors. Understanding the regulation of vascular growth in the placenta will provide much needed insight into placenta-related vascular insufficiencies.

Abortion, Spontaneous↗

PubMed2003

Evidence of a novel isoform of placenta growth factor (PlGF-4) expressed in human trophoblast and endothelial cells.

Placenta growth factor (PlGF), a homodimeric glycoprotein that is homologous to vascular endothelial growth factor (VEGF), is mitogenic to endothelial cells and protects trophoblast from apoptosis. Alternative splicing of mature mRNA gives rise to three known isoforms of PlGF. PlGF is expressed by human trophoblast during normal pregnancy, however, it is not known which isoforms are produced. We have utilized RT-PCR to characterize PlGF isoform expression in normal human trophoblast and umbilical vein endothelial cells (HUVEC). Our results show that PlGF-1, PlGF-2, and PlGF-3 isoforms are expressed by trophoblast and HUVECs. In addition, both cell types also express a novel variant of PlGF, tentatively termed PlGF-4, which has not been previously reported. PlGF-4 consists of the same sequence of PlGF-3, plus the heparin binding domain previously thought to be present only in PlGF-2. Presence of the heparin binding domain in PlGF-4 suggests that this variant would remain cell membrane-associated and thus could influence trophoblast and endothelial cells in an autocrine manner.

Alternative Splicing↗

PubMed2003

Expression and function of placenta growth factor: implications for abnormal placentation.

OBJECTIVE: Essential requirements for successful gestation include the coordinated growth and differentiation of the placenta and the development of a functional placental vasculature. However, relatively little is known about factors that are responsible for regulating these functions. One angiogenic growth factor that might be involved in regulating both vascular endothelial cell and trophoblast function is placental growth factor (PGF). METHODS: Current published reports were surveyed and our own work was reviewed to highlight the expression, function, and potential significance of PGF at the human maternal-fetal interface. RESULTS: PGF is highly expressed in trophoblasts during normal pregnancy, and its expression is significantly decreased in preeclampsia, an obstetric complication presumed to be associated with placental bed hypoxia and ischemia. In agreement with this, in vitro trophoblast expression of PGF can be down-regulated by low oxygen tension. The cognate receptor for PGF, fms-like tyrosine kinase receptor, is expressed on trophoblasts as well as vascular endothelial cells, suggesting that it has autocrine and paracrine functions. Accordingly, PGF can regulate proliferation in first trimester trophoblasts, apoptosis in term trophoblasts, and it can directly or indirectly regulate vascular growth, maturation, and permeability. CONCLUSIONS: Many obstetric complications, most notably preeclampsia, are associated with aberrant trophoblast function and inadequate or dysfunctional vasculature within the developing placenta. The ability of PGF to influence trophoblast and vascular endothelial cells provides clear impetus for further studies to investigate the biological and clinical significance of PGF in normal and abnormal human pregnancies.

Animals↗