maternal-fetal cell transfer, preterm, & other pregnancy related

[Guest guest]

1-Transfer of inflammatory cytokines across the placenta.

2-Lamarckian inheritance by somatically acquired maternal IgG phenotypes.

3-Periodontal disease and poor obstetrical outcome.

4-Circulating Fetal DNA: Its Origin and Diagnostic Potential-A Review.

5-Reciprocal chemokine receptor and ligand expression in the human placenta:

Implications for cytotrophoblast differentiation.

6-Expression and functions of human endogenous retroviruses in the placenta:

an update.

7-The endogenous retroviral locus ERVWE1 is a bona fide gene involved in

hominoid placental physiology.

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Obstet Gynecol. 2004 Mar;103(3):546-50.

Transfer of inflammatory cytokines across the placenta.

Zaretsky MV, JM, Byrd W, Bawdon RE.

Department of Obstetrics and Gynecology, University of Texas Southwestern

Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-9032, USA.

MZARET@...

OBJECTIVE: The purpose of this study was to determine whether the placental

transfer of interleukin (IL)-1alpha, IL-6, and tumor necrosis factor-alpha

(TNF-alpha) occurs.

METHODS: Four normal-term placentas were perfused for maternal-fetal

transfer of the cytokines, 2 placentas for fetal-maternal transfer, and 4

additional placentas were used for an endogenous control. The ex vivo

isolated cotyledon human placental perfusion model was used.

The reference compound antipyrine was used to determine the transport

fraction and clearance index of the cytokines. The cytokines were added to

either the maternal or fetal circulations, and samples were collected for 1

hour in a constant-flow open circulation. Cytokine levels were compared

between the study and control placentas. Concentrations of the cytokines

were measured by sandwich enzyme immunoassay.

RESULTS: The clearance index for the maternal-fetal transfer of IL-1alpha

and TNF-alpha was 0.001, suggesting minimal transfer to the fetal

circulation. The clearance index for IL-6 was 0.30, indicating transfer to

the fetal circulation. When the cytokines were added to the fetal

circulation, the clearance index for IL-1alpha was 0.001, again indicating

minimal transfer. The clearance index for TNF-alpha in the fetal-maternal

study was not determined. IL-6 had a clearance index of 0.23, which was

similar to that observed with maternal-fetal transfer. IL-6 concentrations

in the study placentas were higher than the concentrations found in the

controls.

CONCLUSION: There appears to be bidirectional transfer of IL-6 in the

healthy-term human placental perfusion model. LEVEL OF EVIDENCE: II-2

PMID: 14990420 [PubMed - in process]

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Trends Immunol. 2004 Apr;25(4):180-6.

Lamarckian inheritance by somatically acquired maternal IgG phenotypes.

Lemke H, Coutinho A, Lange H.

Biochemical Institute of the Medical Faculty of the

Christian-Albrechts-University, Kiel, Germany.

Maternal antibodies provide offspring with passive immunity and exert

various active immunostimulatory functions, such as

(i) antimicrobial protection through non-antigen-reactive antibodies, namely

anti-idiotypes,

(ii) allergen-specific suppression of IgE responsiveness and

(iii) under pathological conditions, transfer of autoimmune diseases.

As products of mainly T cell-dependent immune responses with long-lived

antigen-independent plasma cells, maternal IgG molecules have undergone

immune maturation by somatic hypermutations and are therefore acquired

immunological phenotypes representing the collective immunological

experience of the mother.

The inductive function of maternal IgG, although limited to a neonatal

imprinting period, exerts a life-long determinative influence, which can

dominate over seemingly genetic predispositions.

Hence, the functional impact of maternal IgG in offspring appears

phenotypically as a non-genetic inheritance, which thus reveals a Lamarckian

dimension of the immune system.

PMID: 15039044 [PubMed - in process]

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Clin Exp Obstet Gynecol. 2004;31(1):47-9.

Periodontal disease and poor obstetrical outcome.

Carta G, Persia G, Falciglia K, Iovenitti P.

Department of Surgical Science, University of L'Aquila, Unit of Obstetrics

and Gynecology, Avezzano Hospital, Italy.

Maternal infective processes sustained especially by Gram-negative anaerobic

bacteria like periodontal disease, during pregnancy, have been demonstrated

to perturb the physiologic course of parturition through inflammatory

cytokine production, sometimes resulting in preterm labor, preterm premature

rupture of membranes and preterm low birth weight.

In a matched case-control study, the hypothesis that poor oral health of

pregnant women is a risk factor for low birth weight (LBW) was evaluated.

Gingival crevicular fluid levels of PGE2 and IL-1beta were measured in order

to determine whether mediator levels were related to current pregnancy

outcome. Results indicate that GCF-PGE2 and GCF-IL-1beta levels are

significantly higher in preterm low birth weight (PLBW) mothers as compared

with normal birth weight controls. The data confirm that there is a possible

correlation between periodontal problems typical of pregnancy and the

occurrence of complications such as preterm low birth weight.

PMID: 14998188 [PubMed - in process]

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Placenta. 2004 Apr;25 Suppl:S93-S101.

Circulating Fetal DNA: Its Origin and Diagnostic Potential-A Review.

..

Bianchi DW.

Division of Genetics, Departments of Pediatrics, Obstetrics and Gynecology,

Tufts-New England Medical Center and Tufts University School of Medicine,

Box 394, 750 Washington Street, Boston, MA 02111, USA.

OBJECTIVE: In contrast to the traditional teaching that the placenta forms

an impermeable barrier, multiple studies show that both intact fetal cells

and cell-free nucleic acids circulate freely in maternal blood.

Complications of pregnancy, such as pre-eclampsia, or fetal cytogenetic

abnormalities, such as trisomy 21, increase transfusion of both intact fetal

cells and cell-free fetal nucleic acids into the maternal circulation. The

objective of our research is to show that abnormal feto-maternal trafficking

of nucleic acids is associated with fetal and placental pathology, and that

these observations may lead to novel non-invasive diagnostic and screening

tests.

METHODS: Real-time quantitative PCR amplification of DYS1 is used to measure

the levels of male fetal DNA in case-control sets of serum or plasma taken

from pregnant women. In our laboratory, we use DYS1, a Y-chromosome specific

gene, as a uniquely fetal DNA marker for the development of

gestation-specific normal values and theoretical models.

RESULTS: Women carrying fetuses with trisomies 21 or 13 (but not 18) have

increased levels of fetal DNA in their fresh or archived serum and/or plasma

samples. Women destined to develop pre-eclampsia have a characteristic

bi-phasic elevation of cell-free fetal DNA that precedes clinical symptoms.

Data obtained from a variety of clinical scenarios suggest that the placenta

is the predominant source of the circulating fetal nucleic acids, although

apoptotic haematopoietic cells may contribute to the pool as well.

CONCLUSIONS: Fetal cell-free DNA is elevated in a number of conditions

associated with placental pathology. Widespread clinical implementation of

fetal DNA as a screening tool awaits discovery of a reliable

gender-independent marker, which may be DNA polymorphisms, epigenetic

markers, or mRNA. Fetal cell-free nucleic acids have potential for

non-invasive monitoring of placental pathology.

PMID: 15033315 [PubMed - in process]

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Dev Dyn. 2004 Apr;229(4):877-85.

Reciprocal chemokine receptor and ligand expression in the human placenta:

Implications for cytotrophoblast differentiation.

Drake PM, Red-Horse K, Fisher SJ.

Department of Stomatology, University of California San Francisco, San

Francisco, California.

At the onset of pregnancy, the human placenta, which forms the interface

between the embryo/fetus and the mother, must rapidly develop into a

life-sustaining organ. The many unusual processes entailed in placental

development include the poorly understood phenomenon of maternal tolerance

of the hemiallogeneic cells of the conceptus, including, most remarkably,

placental trophoblasts that invade the uterine wall.

To investigate whether this fetal organ exerts control over the maternal

immune system at the level of leukocyte trafficking, we examined placental

expression of chemokines, well-known cytokine regulators of leukocyte

movements. In situ hybridization revealed abundant expression of 13

chemokines in the stromal but not the trophoblast compartment of chorionic

villi. Potential roles for these molecules include recruitment of the

resident macrophage (Hofbauer cell) population to the villi. In parallel,

cytotrophoblast production of a panel of nine chemokine receptors was

assessed by using RNase protection assays.

The numerous receptors detected suggested the novel possibility that the

paracrine actions of chemokine ligands derived from either the villous

stroma or the decidua could mediate general aspects of placental

development, with specific contributions to cytotrophoblast differentiation

along the pathway that leads to uterine invasion. Developmental Dynamics

229:877-885, 2004. Copyright 2004 Wiley-Liss, Inc.

PMID: 15042711 [PubMed - in process]

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Placenta. 2004 Apr;25 Suppl:S16-25.

Expression and functions of human endogenous retroviruses in the placenta:

an update.

Muir A, Lever A, Moffett A.

Research Group in Human Reproductive Immunobiology, Department of Pathology,

University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, UK.

The placenta is unique amongst normal tissues in transcribing many different

human endogenous retrovirus (HERV) families at high levels and this has led

to the suggestion that HERVs may fulfil important functions in reproduction.

This review discusses our current knowledge of the placental expression of

HERVs, in particular the envelope proteins of ERV3 and HERV-W which may have

critical roles in placental function.

PMID: 15033302 [PubMed - in process]

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Proc Natl Acad Sci U S A. 2004 Feb 10;101(6):1731-6. Epub 2004 Feb 02.

The endogenous retroviral locus ERVWE1 is a bona fide gene involved in

hominoid placental physiology.

Mallet F, Bouton O, Prudhomme S, Cheynet V, Oriol G, Bonnaud B, Lucotte G,

Duret L, Mandrand B.

Unite Mixte de Recherche 2142, Centre National de la Recherche

Scientifique-bioMerieux, IFR128 BioSciences Lyon-Gerland, Ecole Normale

Superieure de Lyon, 46 Allee d'Italie, 69364 Lyon Cedex 07, France.

francois.mallet@...

The definitive demonstration of a role for a recently acquired gene is a

difficult task, requiring exhaustive genetic investigations and functional

analysis. The situation is indeed much more complicated when facing

multicopy gene families, because most or portions of the gene are conserved

among the hundred copies of the family.

This is the case for the ERVWE1 locus of the human endogenous retrovirus W

family (HERV-W), which encodes an envelope glycoprotein (syncytin) likely

involved in trophoblast differentiation.

Here we describe, in 155 individuals, the positional conservation of this

locus and the preservation of the envelope ORF. Sequencing of the critical

elements of the ERVWE1 provirus showed a striking conservation among the 48

alleles of 24 individuals, including the LTR elements involved in the

transcriptional machinery, the splice sites involved in the maturation of

subgenomic Env mRNA, and the Env ORF.

The functionality and tissue specificity of the 5' LTR were demonstrated, as

well as the fusogenic activity of the envelope polymorphic variants. Such

functions were also shown to be preserved in the orthologous loci isolated

from chimpanzee, gorilla, orangutan, and gibbon. This functional

preservation among humans and during evolution strongly argued for the

involvement of this recently acquired retroviral envelope glycoprotein in

hominoid placental physiology.

PMID: 14757826 [PubMed - in process]

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