Dataset Information

Assessment of M2/ANXA5 haplotype as a risk factor in couples with placenta-mediated pregnancy complications.

ABSTRACT: PURPOSE:The aim of this study was to confirm the associated M2/ANXA5 carrier risk in women with placenta-mediated pregnancy complications (PMPC) and to test their male partners for such association. Further analysis evaluated the influence of maternal vs. paternal M2 alleles on miscarriage. METHODS:Two hundred eighty-eight couples with preeclampsia (PE), intrauterine growth restriction (IUGR), or premature birth (PB) were recruited (n = 96 of each phenotype). The prevalence of the M2 haplotype was compared to two control cohorts. They included a group of women with a history of normal pregnancy without gestational pathology (Munich controls, n = 94) and a random population sample (PopGen controls, n = 533). RESULTS:Significant association of M2 haplotype and pregnancy complications was confirmed for women and for couples, where prevalence was elevated from 15.4 to 23.8% (p < 0.001). Post hoc analyses demonstrated an association for IUGR and PB individually. A strong link between previous miscarriages and M2 carrier status was identified which may explain the predisposition to placental pregnancy complication. M2/ANXA5 appears to be a risk factor for adverse pregnancy outcomes related, but not limited to miscarriages, with similar prevalence in women and their male partners. CONCLUSION:These findings support the proposed physiological function of ANXA5 as an embryonic anticoagulant that appears deficient in contiguous specter of thrombophilia-related pregnancy complications culminating more frequently in miscarriage in a maternal M2 carrier background.

SUBMITTER: Rogenhofer N

PROVIDER: S-EPMC5758464 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Assessment of M2/ANXA5 haplotype as a risk factor in couples with placenta-mediated pregnancy complications.

Rogenhofer Nina N Nienaber Lara R M LRM Amshoff Lea C LC Bogdanova Nadia N Petroff David D Wieacker Peter P Thaler Christian J CJ Markoff Arseni A

Journal of assisted reproduction and genetics 20170913 1

<h4>Purpose</h4>The aim of this study was to confirm the associated M2/ANXA5 carrier risk in women with placenta-mediated pregnancy complications (PMPC) and to test their male partners for such association. Further analysis evaluated the influence of maternal vs. paternal M2 alleles on miscarriage.<h4>Methods</h4>Two hundred eighty-eight couples with preeclampsia (PE), intrauterine growth restriction (IUGR), or premature birth (PB) were recruited (n = 96 of each phenotype). The prevalence of the ...[more]

PMID: 28900802

Similar Datasets

Project description:Data on the temporal dynamics of human placental gene expression is scarce. We have completed the first whole-genome profiling of human placental gene expression dynamics (GeneChips, Affymetrix®) from early to mid- gestation (10 samples; gestational weeks 5 to 18) and report 154 genes with considerable change in transcript levels (FDR P<0.1). Functional enrichment analysis revealed >200 GO categories that are statistically over-represented among 105 genes with dynamically increasing transcript levels. Analysis in an extended sample (n=43; gestational weeks 5 to 41) conformed a highly significant (FDR P<0.05) expressional peak in mid-gestation placenta for ten genes: BMP5, CCNG2, CDH11, FST, GATM, GPR183, ITGBL1, PLAGL1, SLC16A10, STC1. A central hypothesis of our study states that the aberrant expression of genes characteristic to mid-gestation placenta may contribute to affected fetal growth, maternal preeclampsia (PE) or gestational diabetes (GD). The gene STC1 coding for Stanniocalcin 1 (STC1) was identified with a sharp placental expressional peak in mid-gestation, increased mRNA levels at term and significantly elevated STC1 protein levels in post-partum maternal plasma in all pregnancy complications. The highest STC1 levels were identified in women, who developed simultaneously PE and delivered an SGA baby (median 731 vs 418 pg/ml in controls; P=0.001). CCNG2 and LYPD6 exhibited significantly increased placental mRNA expression and enhanced intensity of immunohistochemistry staining in placental sections all studied in GD and PE cases. Aberrant expression of mid-gestation specific genes in pregnancy complications at term indicates the importance of the fine-scale tuning of the temporal dynamics of transcription regulation in placenta. Observed significantly elevated plasma STC1 in complicated pregnancies warrants further investigations of its potential as a biomarker. Interestingly, a majority of genes with high expression in mid-gestation placenta have also been implicated in adult complex disease. This observation promotes a recently opened discussion on the role of placenta in developmental programming. 4 samples; this submission is extension of our earlier study (accession GSE22490).

Project description:Background: Second-trimester uterine artery Doppler is a well-established tool for the prediction of preeclampsia and fetal growth restriction. At delivery, placentas from affected pregnancies may have gross pathologic findings. Some of these features are detectable by ultrasound, but the relative importance of placental morphologic assessment and uterine artery Doppler in mid-pregnancy is presently unclear. Objective: To characterize the association of second-trimester sonographic placental morphology markers with placenta-mediated complications and determine whether these markers are predictive of placental dysfunction independent of uterine artery Doppler. Methods: This was a retrospective cohort study of patients with a singleton pregnancy at high risk of placental complications who underwent a sonographic placental study at mid-gestation (160/7−246/7 weeks’ gestation) in a single tertiary referral center between 2016–2019. The sonographic placental study included assessment of placental dimensions (length, width, and thickness), placental texture appearance, umbilical cord anatomy, and uterine artery Doppler (mean pulsatility index and early diastolic notching). Placental area and volume were calculated based on placental length, width, and thickness. Continuous placental markers were converted to multiples on medians (MoM). The primary outcome was a composite of early-onset preeclampsia and birthweight < 3rd centile. Results: A total of 429 eligible patients were identified during the study period, of whom 45 (10.5%) experienced the primary outcome. The rate of the primary outcome increased progressively with decreasing placental length, width, and area, and increased progressively with increasing mean uterine artery pulsatility index (PI). By contrast, placental thickness followed a U-shaped relationship with the primary outcome. Placental length, width, and area, mean uterine artery PI and bilateral uterine artery notching were all associated with the primary outcome. However, in the adjusted analysis, the association persisted only for placenta area (adjusted odds ratio [aOR] 0.21, 95%-confidence interval [CI] 0.06–0.73) and mean uterine artery PI (aOR 11.71, 95%-CI 3.84–35.72). The area under the ROC curve was highest for mean uterine artery PI (0.80, 95%-CI 0.71–0.89) and was significantly higher than that of placental area (0.67, 95%-CI 0.57–0.76, p = 0.44). A model that included both mean uterine artery PI and placental area did not significantly increase the area under the curve (0.82, 95%-CI 0.74–0.90, p = 0.255), and was associated with a relatively minor increase in specificity for the primary outcome compared with mean uterine artery PI alone (63% [95%-CI 58–68%] vs. 52% [95%-CI 47–57%]). Conclusion: Placental area is independently associated with the risk of placenta-mediated complications yet, when combined with uterine artery Doppler, did not further improve the prediction of such complications compared with uterine artery Doppler alone.

Project description:Despite the importance of placenta in mediating rapid physiological changes in pregnancy, data on temporal dynamics of placental gene expression are limited. We completed the first transcriptome profiling of human placental gene expression dynamics (GeneChips, Affymetrix®; ~47,000 transcripts) from early to mid-gestation (n = 10; gestational weeks 5-18) and report 154 genes with significant transcriptional changes (ANOVA, FDR P<0.1). TaqMan RT-qPCR analysis (n = 43; gestational weeks 5-41) confirmed a significant (ANOVA and t-test, FDR P<0.05) mid-gestational peak of placental gene expression for BMP5, CCNG2, CDH11, FST, GATM, GPR183, ITGBL1, PLAGL1, SLC16A10 and STC1, followed by sharp decrease in mRNA levels at term (t-test, FDR P<0.05). We hypothesized that normal course of late pregnancy may be affected when genes characteristic to mid-gestation placenta remain highly expressed until term, and analyzed their expression in term placentas from normal and complicated pregnancies [preeclampsia (PE), n = 12; gestational diabetes mellitus (GDM), n = 12; small- and large-for-gestational-age newborns (SGA, LGA), n = 12+12]. STC1 (stanniocalcin 1) exhibited increased mRNA levels in all studied complications, with the most significant effect in PE- and SGA-groups (t-test, FDR P<0.05). In post-partum maternal plasma, the highest STC1 hormone levels (ELISA, n = 129) were found in women who had developed PE and delivered a SGA newborn (median 731 vs 418 pg/ml in controls; ANCOVA, P = 0.00048). Significantly higher expression (t-test, FDR P<0.05) of CCNG2 and LYPD6 accompanied with enhanced immunostaining of the protein was detected in placental sections of PE and GDM cases (n = 15). Our study demonstrates the importance of temporal dynamics of placental transcriptional regulation across three trimesters of gestation. Interestingly, many genes with high expression in mid-gestation placenta have also been implicated in adult complex disease, promoting the discussion on the role of placenta in developmental programming. The discovery of elevated maternal plasma STC1 in pregnancy complications warrants further investigations of its potential as a biomarker.

Dataset Information

Assessment of M2/ANXA5 haplotype as a risk factor in couples with placenta-mediated pregnancy complications.

Publications

Assessment of M2/ANXA5 haplotype as a risk factor in couples with placenta-mediated pregnancy complications.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets