Biomedical subjects

E K Moses

Publications and source records attributed to E K Moses.

At least 19 recordsLinked to original sources

PubMed2006

Identification of two novel quantitative trait loci for pre-eclampsia susceptibility on chromosomes 5q and 13q using a variance components-based linkage approach.

Pre-eclampsia/eclampsia (PE/E) is a common and serious disorder of human pregnancy that is associated with substantial maternal and perinatal morbidity and mortality. The suspected aetiology of PE/E is complex, with susceptibility being attributable to multiple environmental factors and a large genetic component. By assuming that the underlying liability towards PE/E susceptibility is inherently quantitative, any PE/E susceptibility gene would represent a quantitative trait locus (QTL). This assumption enables a more refined and powerful variance components procedure using a threshold model for our PE/E statistical analysis. Using this more efficient linkage approach, we have now re-analysed our previously completed Australian/New Zealand genome scan data to identify two novel PE/E susceptibility QTLs on chromosomes 5q and 13q. We have obtained strong evidence of linkage on 5q with a peak logarithm-of-odds (LOD) score of 3.12 between D5S644 and D5S433 [at approximately 121 centimorgan (cM)] and strong evidence of linkage on 13q with a peak LOD score of 3.10 between D13S1265 and D13S173 (at approximately 123 cM). Objective identification and prioritization of positional candidate genes using the quantitative bioinformatics program GeneSniffer revealed highly plausible PE/E candidate genes encoding aminopeptidase enzymes and a placental peptide hormone on the 5q QTL and two type IV collagens on the 13q QTL regions, respectively.

Analysis of Variance↗

PubMed2006

Objective prioritization of positional candidate genes at a quantitative trait locus for pre-eclampsia on 2q22.

Pre-eclampsia/eclampsia (PE/E) is a common, serious medical disorder of human pregnancy. Familial association of PE/E has been recognized for decades, but the genetics are complex and poorly understood. In an attempt to identify PE/E susceptibility genes, we embarked on a positional cloning strategy using 34 Australian and New Zealand PE/E pedigrees. An initial 10-cM resolution genome scan revealed a putative susceptibility locus spanning a broad region on chromosome 2 that overlaps an independently determined linkage signal seen in Icelandic PE pedigrees. Subsequent fine mapping using 25 additional short tandem repeat (STR) markers in this region and non-parametric multipoint linkage analysis did not change the overall position. Under a strict diagnosis of PE, we obtained significant evidence of linkage on 2q with a peak log-of-odds ratio score (LOD) of 3.43 near marker D2S151 at 155 cM. To prioritize positional candidate genes at the 2q locus for detailed analysis, we applied an objective prioritization strategy that integrates quantitative bioinformatics, assessment of differential gene expression and association analysis of single-nucleotide polymorphisms (SNPs). Highest priority was assigned to the activin receptor gene ACVR2. This gene also showed >10-fold differential gene expression in human decidual tissue from normotensive and PE individuals. We genotyped five known SNPs in this gene in our pedigrees and performed tests for association and linkage disequilibrium. One SNP (rs1424954) showed strong preliminary evidence of association with PE (P = 0.007), whereas two others (rs1364658 and rs1895694) exhibited nominal evidence (P < 0.05). Haplotype analysis revealed no additional association information. There was evidence of weak linkage disequilibrium among these SNPs. The highest observed LD occurred between the two strongest associated SNPs, suggesting that the observed signals may be the signature of an observed functional variant.

Activin Receptors, Type II↗

PubMed2005

Gene expression of the constant region of the heavy chain of immunoglobulin G (IgG CRHC) is down-regulated in human decidua in association with preeclampsia.

An aberrant interaction at the maternal/fetal interface between the genetically distinct fetal trophoblast cells and cells of the maternal decidua has been proposed as an initiating factor in one of the major complications of human pregnancy, preeclampsia. Biochemical and epidemiological studies suggest that the immune system plays an important role in preeclampsia. Thus, the aim of this study was to determine the decidual gene expression status in preeclampsia of one of the key components of the adaptive immune system. Total RNA was extracted from decidua collected from women with normal pregnancies and those complicated by preeclampsia. Reverse Northern analysis was performed on 72 cDNAs from human decidua and differentially expressed genes identified were analysed further using semi-quantitative RT-PCR and Northern blot analysis. Expression of the gene encoding the constant region of the heavy chain of immunoglobulin G (IgG CRHC) was shown to be down-regulated in association with preeclampsia. These data support the hypothesis that immune maladaptation may play an important role in the pathogenesis of preeclampsia.

Decidua↗

PubMed2005

Detection of CAG repeats in pre-eclampsia/eclampsia using the repeat expansion detection method.

Pre-eclampsia/eclampsia is a serious disorder of human pregnancy that has a worldwide incidence of 2-10% and carries a severe morbidity and mortality risk for both mother and child. Its precise cause remains unknown. However, there is increasing evidence of an underlying complex maternal genetic susceptibility. Its high population incidence in the face of strong negative selection pressure suggests that the gene(s) involved have a selective advantage and/or a high mutation rate. One class of genetic diseases that involve a high mutation rate are the trinucleotide repeat expansion diseases. Thus, the aim of this study was to determine whether there is an association between a trinucleotide (CAG) repeat expansion and pre-eclampsia/eclampsia. We have used the repeat expansion detection (RED) method, which was developed to directly identify clinically significant repeat expansions, to analyse genomic DNA from an Australian and New Zealand population. The maximal CAG repeat length for each individual was recorded and the Mann-Whitney U and Wilcoxon rank sum test for independent samples were used to compare distributions for CAG/CTG repeats between two populations. There were no statistically significant differences between the distribution of CAG repeats in normotensive (n = 59) and severe pre-eclampsia (n = 69) (Mann-Whitney U = 1732; P = 0.14), and normotensive (n = 59) and eclamptic (n = 15) populations (Mann-Whitney U = 417, P = 0.726). Therefore, these RED results do not support a role for a large CAG expansion in pre-eclampsia/eclampsia. However, these data do not preclude the possibility that a small CAG expansion is associated with the disorder nor do they negate the hypothesis that a highly mutable gene contributes to the genetic component of pre-eclampsia/eclampsia.

Autoradiography↗

PubMed2004

Fine mapping and SNP analysis of positional candidates at the preeclampsia susceptibility locus (PREG1) on chromosome 2.

Genome scans in Icelandic, Australian and New Zealand, and Finnish families have localized putative susceptibility loci for preeclampsia/ eclampsia to chromosome 2. The locus mapped in the Australian and New Zealand study (designated PREG1) was thought to be the same locus as that identified in the Icelandic study. In both these studies, two distinct quantitative trait locus (QTL) regions were evident on chromosome 2. Here, we describe our fine mapping of the PREG1 locus and a genetic analysis of two positional candidate genes. Twenty-five additional microsatellite markers were genotyped within the 74-cM linkage region defined by the combined Icelandic and Australian and New Zealand genome scans. The overall position and shape of the localization evidence obtained using nonparametric multipoint analysis did not change from that seen previously in our 10-cM resolution genome scan; two peaks were displayed, one on chromosome 2p at marker D2S388 (107.46 cM) and the other on chromosome 2q at 151.5 cM at marker D2S2313. Using the robust two-point linkage analysis implemented in the Analyze program, all 25 markers gave positive LOD scores with significant evidence of linkage being seen at marker D2S2313 (151.5 cM), achieving a LOD score of 3.37 under a strict diagnostic model. Suggestive evidence of linkage was seen at marker D2S388 (107.46 cM) with a LOD score of 2.22 under the general diagnostic model. Two candidate genes beneath the peak on chromosome 2p were selected for further analysis using public single nucleotide polymorphisms (SNPs) within these genes. Maximum LOD scores were obtained for an SNP in TACR1 (LOD = 3.5) and for an SNP in TCF7L1 (LOD = 3.33), both achieving genome-wide significance. However, no evidence of association was seen with any of the markers tested. These data strongly support the presence of a susceptibility gene on chromosome 2p11-12 and substantiate the possibility of a second locus on chromosome 2q23.

Australia↗

PubMed2003

Searching for candidate genes for male infertility.

AIM: We describe an approach to search for candidate genes for male infertility using the two human genome databases: the public University of California at Santa Cruz (UCSC) and private Celera databases which list known and predicted gene sequences and provide related information such as gene function, tissue expression, known mutations and single nucleotide polymorphisms (SNPs). METHODS AND RESULTS: To demonstrate this in silico research, the following male infertility candidate genes were selected: (1) human BOULE, mutations of which may lead to germ cell arrest at the primary spermatocyte stage, (2) mutations of casein kinase 2 alpha genes which may cause globozoospermia, (3) DMR-N9 which is possibly involved in the spermatogenic defect of myotonic dystrophy and (4) several testes expressed genes at or near the breakpoints of a balanced translocation associated with hypospermatogenesis. We indicate how information derived from the human genome databases can be used to confirm these candidate genes may be pathogenic by studying RNA expression in tissue arrays using in situ hybridization and gene sequencing. CONCLUSION: The paper explains the new approach to discovering genetic causes of male infertility using information about the human genome.

Casein Kinase II↗

PubMed2001

C677T methylenetetrahydrofolate reductase polymorphism is not a risk factor for pre-eclampsia/eclampsia among Australian women.

The C677T methylenetetrahydrofolate reductase (MTHFR) gene polymorphism results in reduced MTHFR enzymatic activity. This in turn results in increased levels of homocysteine. It has been suggested that increased levels of homocysteine cause vascular disease, which is known to increase the risk of developing pre-eclampsia (PE) during pregnancy. However, recent studies on Japanese, Italian and American populations have failed to reach agreement on an association between the C677T polymorphism and PE. In this study, 156 cases of eclampsia (E)/PE and 79 normal pregnant control cases from an Australian population were genotyped for this mutation. No significant difference could be found in the incidence of the homozygote mutation or in the allele frequency. We conclude from this study that the C677T mutation in our population is not associated with the development of PE/E.

Australia↗

PubMed2000

A genome scan in families from Australia and New Zealand confirms the presence of a maternal susceptibility locus for pre-eclampsia, on chromosome 2.

Epidemiological studies have shown that genetic factors contribute to the etiology of the common and serious pregnancy-specific disorder pre-eclampsia (PE)/eclampsia (E). Candidate-gene studies have provided evidence (albeit controversial) of linkage to several genes, including angiotensinogen on 1q42-43 and eNOS on 7q36. A recent medium-density genome scan in Icelandic families identified significant linkage to D2S286 (at 94.05 cM) on chromosome 2p12 and suggestive linkage to D2S321 (at 157.5 cM) on chromosome 2q23. In the present article, the authors report the results of a medium-density genome scan in 34 families, representing 121 affected women, from Australia and New Zealand. Multipoint nonparametric linkage analysis, using the GENEHUNTER-PLUS program, showed suggestive evidence of linkage to chromosome 2 (LOD=2.58), at 144.7 cM, between D2S112 and D2S151, and to chromosome 11q23-24, between D11S925 and D11S4151 (LOD=2.02 at 121.3 cM). Given the limited precision of estimates of the map location of disease-predisposing loci for complex traits, the present finding on chromosome 2 is consistent with the finding from the Icelandic study, and it may represent evidence of the same locus segregating in the population from Australia and New Zealand. The authors propose that the PE/E-linked locus on chromosome 2p should be designated the "PREG1" (pre-eclampsia, eclampsia gene 1) locus.

Australia↗

PubMed2000

Differential mRNA expression of urokinase-type plasminogen activator, plasminogen activator receptor and plasminogen activator inhibitor type-2 in normal human endometria and endometrial carcinomas.

OBJECTIVE: Extracellular proteolytic degradation is an essential part of cellular invasive processes. The increased proteolytic activity observed in invasive cancers, mediated through the activitation of components of the plasminogen activation system, has been demonstrated in various human tumors. The aim of this study was to determine the level of mRNA expression for the genes encoding urokinase (uPA), urokinase receptor (uPAR), and plasminogen activator inhibitor (PAI-2) in endometrial carcinomas. METHODS: In this study, the expression of uPA, uPAR, and PAI-2 mRNA was examined in normal endometrial tissue (n = 16) and endometrial carcinoma tissues (n = 34) by Northern blot analysis. RESULTS: Compared to the controls, the relative abundance of uPAR was significantly elevated in all of the clinical stages of malignancy examined, with a 33-fold increase in mRNA expression from normal endometria to advanced clinical stage carcinomas (Stage III, P < 0.0001). Similarly, uPA was significantly elevated in all clinical stages examined when compared to the normal group, with a 16-fold increase in mRNA expression in advanced stage carcinomas (P < 0.0005). The expression of both uPA and uPAR mRNA also increased with each progression in clinical stage. Expression of the inhibitor, PAI-2, was significantly up-regulated by 5-fold in only the late stages of endometrial tumor development (P < 0.001), while Stage IB and IC carcinomas did not express high levels of PAI-2 mRNA. CONCLUSION: These data indicate that components of the plasminogen activation cascade are up-regulated in progressive stages of invasive endometrial cancer and are consistent with their role in determining invasive potential of endometrial carcinomas.

Endometrial Neoplasms↗

PubMed2000

Differential expression of the alpha(2)-macroglobulin receptor and the receptor associated protein in normal human endometrium and endometrial carcinoma.

Extracellular matrix degradation, mediated by the activation of receptor-bound proteolytic enzymes, is essential to the process of cellular invasion. Many normal physiological functions such as endometrial remodelling are reliant on the activation of these surface associated proteolytic enzymes, as are pathological functions such as cancer-cell invasion. The internalization of proteolytic complexes is mediated by the multi-functional clearance receptor, alpha(2)-macroglobulin receptor/LRP. The role of LRP and its ligand binding inhibitor, the receptor-associated protein (RAP), in the advancement of invasive endometrial carcinoma is unknown. The aim of this study was to compare the expression of LRP and RAP mRNA in normal endometrium (n = 14) and endometrial carcinoma (n = 33) by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR). Expression of LRP mRNA in normal endometrium was significantly increased in the secretory phase when compared with proliferative phase endometrium (P: < 0.05). The expression of LRP in all carcinomas examined was significantly reduced to about 20% of the amount in normal endometrium (P: < 0.05), whereas RAP expression was not significantly different between endometrium and carcinoma. No significant difference in the level of LRP or RAP expression was observed between carcinoma grades or stages. In conclusion, we have shown that LRP expression is differentially regulated in the normal endometrium during the menstrual cycle and is decreased in invasive endometrial carcinomas.

Adenocarcinoma↗

PubMed2000

Identification and partial characterization of differentially expressed mRNAs in normal human endometria and endometrial carcinomas by differential display RT-PCR.

Differential display methodology was employed to examine and compare the mRNA species derived from normal endometrial tissue and endometrial carcinoma (grade 3, stage III) tissue biopsies. Two cDNA sequences, one expressed in the tumour group only (T19) and the other expressed only in the normal group (N22), were selected for verification of differential expression by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR). The expression of N22 was restricted to the normal group, suggesting a possible tumour suppressing function. Sequence analysis of this fragment revealed a high degree of similarity to a human cDNA sequence of unknown function. The expression of T19 mRNA was observed in both normal and neoplastic tissues, however the relative abundance was significantly higher in endometrial carcinomas. Expression of T19 mRNA was further examined in a larger clinical sample set and was significantly increased in the tumours (n = 16), with a three-fold increase when compared with the normal endometria, n = 5 (Kruskal-Wallis analysis of variance, P<0.05). Subsequent sequence analysis of T19 revealed a high degree of similarity to the 3' untranslated region of a rat growth factor responsive gene, SM-20. Further characterization of these mRNA transcripts may lead to the identification of novel genes involved in endometrial tumourogenesis.

3' Untranslated Regions↗

PubMed2000

Methylenetetrahydrofolate reductase polymorphisms are not a risk factor for pre-eclampsia/eclampsia in Australian women.

In European and Japanese but not in Australian, American, and South African women, the C677T methylenetetrahydrofolate reductase (MTHFR) polymorphism has been reported to be a genetic risk factor pre-eclampsia/eclampsia (PE/E). The recently described A1298C MTHFR gene polymorphism also results in reduced MTHFR enzyme activity, although to a lesser extent than the previously described C677T polymorphism. Heterozygotes for both polymorphisms are reported to have an even lower MTHFR enzymatic activity than seen in homozygotes for the C677T genotype. In this current study we determined the allele frequency of the A1298C MTHFR gene polymorphism in an Australian population and examined this polymorphism alone and in combination with the C677T MTHFR polymorphism for an association with PE/E. Neither the A1298C polymorphism alone nor a combination of both polymorphisms showed an association with PE/E in our population of Australian women.

Alleles↗

PubMed2000

Prothrombin G20210A mutation: is it associated with pre-eclampsia?

OBJECTIVE: A strong independent association between the prothrombin G20210A gene mutation and pre-eclampsia has been reported in an Italian population. This result was not confirmed in a subsequent study in a Dutch population. The objective of this study was to further test the hypothesis that the prothrombin G20210A mutation is associated with pre-eclampsia/eclampsia. METHODS: Seventeen eclamptics and 67 pre-eclamptics were recruited from 34 multicase Australian/New Zealand families. An additional 105 unrelated pre-eclamptic/eclamptic women and 119 parous women were recruited as controls. RESULTS: The overall incidence for the prothrombin G20210A gene mutation in the pre-eclamptic group was 3.6% (95% CI 1.2-8.2%) which was not significantly different from the control group 2.5% (95% CI 0.5-7.2%) (p = 0.73, OR 1.44, 95% CI 0.34-6.17). CONCLUSION: This study provides little evidence of a significant relationship between the prothrombin G20210A gene mutation and pre-eclampsia. Based on our results, we do not recommend testing for the prothrombin G20210A mutation in the routine investigation of women with pre-eclampsia.

Adult↗

PubMed2000

Magnesium regulates hypoxia-stimulated apoptosis in the human placenta.

Apoptosis (programmed cell death) in the human placenta is likely to play a major role in determining the structure and function of that organ. Fetal growth restriction (FGR) has been shown to be associated with increased levels of placental apoptosis. Altered regulation of apoptosis may play an important pathophysiological role in FGR. As reduced placental perfusion and reduced oxygenation are features of FGR, one aim of this study was to determine the effects of hypoxia on apoptotic activity, as assessed by DNA laddering, of placental tissue in vitro. In addition, levels of placental apoptosis may be affected by pharmacological agents routinely used in obstetric patient management. Thus an additional aim of this study was to determine the effects of several relevant pharmacological agents on the levels of DNA laddering during in vitro incubation of human placentae under hypoxic conditions. Incubation of normal placental explant tissue at 37 degrees C for 1-2 h under hypoxic conditions significantly increased placental DNA laddering compared with that in non-incubated tissue, whereas levels of DNA laddering during incubation for up to 2 h under normoxic conditions were not significantly higher than those in non-incubated tissue. The DNA laddering activity of placental explants after 2 h of incubation under hypoxic conditions was significantly increased with increased concentrations of magnesium, but remained unchanged by the inclusion of pethidine, aspirin, nifedipine, dexamethasone, heparin or indomethacin in the incubation mixture. These results suggest that hypoxia may stimulate apoptotic activity in cultured human placental tissues, and that hypoxia-stimulated placental apoptosis may be further increased by increasing the extracellular magnesium concentration.

Apoptosis↗

PubMed1999

Genetic susceptibility to pre-eclampsia and chromosome 7q36.

Pre-eclampsia is the most common serious medical disorder of human pregnancy. The human endothelial cell nitric oxide synthase (eNOS) gene is a candidate for pre-eclampsia/eclampsia (PE/E) susceptibility. A linkage study was performed on Australian PE/E families using 25 microsatellite markers from chromosome 7, one of which (eNOS-CA) resides within the eNOS gene. No significant linkage was found for the eNOS-CA marker using either parametric or non-parametric analysis. However, D7S 1805 from the eNOS gene region on 7q36, gave a suggestion of linkage using parametric analysis (maximum LOD score =2.143 at theta=0.14) and non-parametric APM analysis (T1/sqrt(p)=3.53; P=0.002). Further, an association study was performed on unrelated PE/E cases and controls from both Chinese and Australian populations to test for a relationship between the eNOS gene and PE/E. No association was found between the eNOS-CA marker and PE/E in either population. However, there was a significant difference in the allelic distribution of eNOS-CA between the two ethnic groups. The linkage results support the possibility that a susceptibility locus for pre-eclampsia resides in the 7q36 region, however, there is no definitive evidence to support the notion that the eNOS gene itself is responsible for susceptibility to pre-eclampsia.

Asian People↗

PubMed1999

Alternative forms of a novel aspartyl protease gene are differentially expressed in human gestational tissues.

The aim of this study was to identify genes involved in human placentation. To do this, differential gene expression was assessed in the decidua (placental bed) from pre-eclamptic and normotensive pregnancies using the polymerase chain reaction (PCR)-based subtractive technique of representational difference analysis. A novel aspartyl protease (cathepsin D-like) cDNA sequence was isolated by virtue of its over-expression in the pre-eclamptic decidual sample tested. It was designated DAP-1 (for Decidual Aspartyl Protease 1). Using DAP-1 primer sequences a second cDNA (DAP-2) was subsequently isolated from decidual RNA by reverse transcription (RT)-PCR and found to be identical to DAP-1 apart from 80 additional and consecutive base pairs in the N-terminal coding region. In DAP-2, a stop codon within the unique 80 bp sequence was predicted to terminate translation immediately before the consensus active site residues. While Southern blotting was used to show that there are two loci with homology to DAP-1 in the human genome, it is postulated that alternative pre-mRNA splicing of the 80 bp exon is involved in the regulated expression of active (DAP-1) and inactive (DAP-2) forms of this novel protease; a mechanism similar to that involved in the regulated expression of Caspase-2, a protease involved in apoptosis. In other systems the regulation of alternative splicing is indicated by tissue specificity and developmental stage specificity of the various spliced products. In this context it was demonstrated that whereas DAP-1 was the major transcript expressed in decidua, the pattern was reversed in the adjacent placental tissue. It is proposed that tissue and developmental stage-specific expression of the DAP protease are important for the normal development and function of the uteroplacental tissues and that dysregulation of the control of DAP gene splicing may play a role in abnormal placentation, like that seen in pre-eclampsia.

Alternative Splicing↗

PubMed1999

The eNOS gene: a candidate for the preeclampsia susceptibility locus?

OBJECTIVE: To investigate the endothelial cell nitric oxide synthase (eNOS) gene as a candidate for susceptibility to preeclampsia. METHODS: Twenty-six Australian families containing 11 eclamptics, 59 severe preeclamptics, and 27 mild preeclamptics were used to test for linkage between the eNOS gene region and preeclampsia. Two microsatellite markers (D7S483 and D7S505) in the proximity of the eNOS gene were used. MAIN OUTCOME MEASURES: Logarithm of odds (LOD) scores were used to examine the cosegregation of alleles with the disease under a variety of inheritance models. Model-independent analysis, affected pedigree member method (AFFPED), and pairwise haplotype sharing between affected sibs were also used. RESULTS: Two-point LOD score analysis gave no evidence of linkage between preeclampsia and two markers in close proximity to the eNOS gene (LOD scores < 1) for any of the inheritance models investigated, with no evidence of heterogeneity between pedigrees. The AFFPED and the pairwise haplotype sharing test on affected sibs also gave no evidence of linkage (p-values > 0.05). CONCLUSION: This study provides no evidence for linkage between two markers in close proximity to the eNOS gene and preeclampsia in these families. These results do not support the recent suggestion that eNOS could be a familial pregnancy-induced hypertension gene (Arngrimsson R, et al., Am J Hum Genet 1997;61:354-62). Distinguishing preeclampsia from other hypertensive disorders in pregnancy is difficult. Hypertension appears to be a consequence, rather than a primary cause of preeclampsia. Given the vasodilatory role of the eNOS gene product, it is possible that the linkage recently reported for eNOS reflects its relationship with hypertension rather than preeclampsia.

Australia↗

PubMed1998

Distribution of the phospholipase A2 receptor messenger RNA in human gestational tissues.

Recently, a model has been proposed for the involvement of secretory phospholipase A2 (sPLA2) in the onset of and/or progression of human labour via the metabolism of cell membrane glycerophospholipids to generate biologically active, phospholipid-derived mediators. The recent molecular cloning and characterization of a cell-surface receptor for sPLA2 raise the possibility that sPLA2 enzymes may also affect cell function in intrauterine tissues via a receptor-mediated pathway. The aim of this study was to determine the expression profile of the PLA2 receptor messenger RNA in human gestational tissues at term. Messenger RNA for the PLA2 receptor was detected in amnion, choriodecidua and placenta by RT-PCR and transcripts of similar size to the 6.5- and 5.4-kb transcripts previously reported in various other human tissues were detected in choriodecidua by Northern blot analysis. However, smaller transcripts of approximately 4, 2.3 and 1 kb were also detected in choriodecidua by Northern blot analysis and the 2.3-kb transcript and the 1-kb transcript were the only major transcripts detected in amnion and placenta, respectively. The presence of PLA2 receptor mRNA in human gestational tissues indicates that an alternative non-catalytic pathway may contribute to the regulatory effects of sPLA2 isozymes in these tissues. While the specificity and affinity of the various transcripts identified in this study have yet to be determined, PLA2 isozymes released from human gestational tissues during pregnancy and at the time of labour may function as paracrine or autocrine mediators to affect cell function.

Amnion↗