Review: placental biomarkers for assessing fetal health

Manokhina, Irina; Gobbo, Giulia; Konwar, Chaini; Wilson, Samantha L.; Robinson, Wendy P.

doi:10.1093/hmg/ddx210

Cited by 41 publications

(33 citation statements)

References 79 publications

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“…42 It has been demonstrated that the maternal environment determines the structure and function of the placenta, with consequences on the development of the foetus. 43,44 In the present study, we observed an increase in the expression of NTF4 in the placenta of very active mothers as an adaptive response to maternal physical activity. NTF4 is related to placental growth and inhibition of apoptosis promoting the survival of placental cells.…”

supporting

confidence: 61%

Maternal physical activity-induced adaptive transcriptional response in brain and placenta of mothers and rat offspring

Fragoso¹,

Santos²,

Silva³

et al. 2019

J Dev Orig Health Dis

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Maternal physical activity induces brain functional changes and neuroplasticity, leading to an improvement of cognitive functions, such as learning and memory in the offspring. This study investigated the effects of voluntary maternal physical activity on the gene expression of the neurotrophic factors (NTFs): BDNF, NTF4, NTRK2, IGF-1 and IGF-1r in the different areas of mother’s brain, placenta and foetus brain of rats. Female Wistar rats (n = 15) were individually housed in voluntary physical activity cages, containing a running wheel, for 4 weeks (period of adaptation) before gestation. Rats were classified as inactive (I, n = 6); active (A, n = 4) and very active (VA, n = 5) according to daily distance spontaneously travelled. During gestation, the dams continued to have access to the running wheel. At the 20th day of gestation, gene expression of NTFs was analysed in different areas of mother’s brain (cerebellum, hypothalamus, hippocampus and cortex), placenta and the offspring’s brain. NTFs gene expression was evaluated using quantitative PCR. Very active mothers showed upregulation of IGF-1 mRNA in the cerebellum (36.8%) and NTF4 mRNA expression in the placenta (24.3%). In the cortex, there was a tendency of up-regulation of NTRK2 mRNA (p = 0.06) in the A and VA groups when compared to I group. There were no noticeable changes in the gene expression of NTFs in the offspring’s brain. Our findings suggest the existence of a developmental plasticity induced by maternal physical activity in specific areas of the brain and placenta representing the first investment for offspring during development.

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supporting

confidence: 61%

Maternal physical activity-induced adaptive transcriptional response in brain and placenta of mothers and rat offspring

Fragoso¹,

Santos²,

Silva³

et al. 2019

J Dev Orig Health Dis

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“…Serial maternal blood sampling is routine in medical care and research. Maternal blood enables direct measures of maternal factors, foetal‐derived material (eg cell‐free nucleic acids, foetal cells) and placenta‐derived material (eg nano‐sized extracellular vesicles, microvesicles, exosomes) . Material leftover from prenatal testing can be studied .…”

Section: Resultsmentioning

confidence: 99%

“…Maternal blood enables direct measures of maternal factors, foetal-derived material (eg cell-free nucleic acids, foetal cells) 58,59 and placenta-derived material (eg nano-sized extracellular vesicles, microvesicles, exosomes). 60,61 Material leftover from prenatal testing can be studied. 63,64 At delivery, cord blood can be sampled and placentas can be measured and studied.…”

Section: Biospecimen Procurementmentioning

confidence: 99%

The national blueprint for pregnancy/birth longitudinal cohorts to study factor VIII immunogenicity: NHLBI State of the Science (SOS) Workshop on factor VIII inhibitors

Johnsen

Brown

2019

Haemophilia

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Introduction Patients with haemophilia can develop inhibitors to exogenous coagulation factors. Some patients are tolerant to factor, while those who develop inhibitors do so early in life. Genetics and environmental factors are known to contribute to inhibitor risk. However, it is not yet possible to predict inhibitor formation or treatment responsiveness in individuals. We hypothesize that factors in the antenatal/neonatal period inform inhibitor risk development. Aim To consider the design of longitudinal studies beginning in the antenatal/neonatal period and the use of new technologies to better understand haemophilia inhibitors. Methods A working group was formed for the NHLBI State of the Science Workshop: Factor VIII Inhibitors: Generating a National Blueprint for Future Research to solicit input from the US haemophilia community and international collaborators to consider design of pregnancy/birth longitudinal cohorts that leverage ‐omics, existing phenotypic data, and in silico modelling to study inhibitors. Results An antenatal/neonatal longitudinal cohort should begin with enrolment of pregnant genetic carriers of haemophilia and span the at‐risk period for inhibitor development in the child. Data and samples from the mother, placenta, neonate and young child can be obtained that are amenable to existing assays, genomics and other ‐omics studies. Data can inform in silico prediction and mathematical models. Conclusion A longitudinal study beginning before birth offers the unique opportunity to study factors that influence inhibitor development prior to exposure. Advances in ‐omics and computational biology can study complex phenotypes in this rare disease. This study could be accomplished through interdisciplinary efforts and patient community engagement.

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“…In our study, we were successful in confirming some of our array-wide DNAm findings by an alternate technology and validating these DNAm results in an independent set of samples. These DNAm alterations may be useful in the development of biomarkers for rapid prenatal detection of aCA if they are also detectable in maternal blood [ 79 ], as has been shown for other conditions including cancer [ 80 – 83 ] and preeclampsia [ 84 , 85 ]. However, the aCA-associated methylation changes reported in this study were small in magnitude and may require highly sensitive detection methods.…”

Section: Discussionmentioning

confidence: 99%

DNA methylation profiling of acute chorioamnionitis-associated placentas and fetal membranes: insights into epigenetic variation in spontaneous preterm births

Konwar

Price

Wang

et al. 2018

Epigenetics & Chromatin

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BackgroundPlacental inflammation, often presenting as acute chorioamnionitis (aCA), is commonly associated with preterm birth. Preterm birth can have both immediate and long-term adverse effects on the health of the baby. Developing biomarkers of inflammation in the placenta can help to understand its effects and potentially lead to new approaches for rapid prenatal diagnosis of aCA. We aimed to characterize epigenetic variation associated with aCA in placenta (chorionic villi) and fetal membranes (chorion and amnion) to better understand how aCA may impact processes that lead to preterm birth. This study lays the groundwork for development of novel biomarkers for aCA.MethodsSamples from 44 preterm placentas (chorionic villi) as well as matched chorion and amnion for 16 of these cases were collected for this study. These samples were profiled using the Illumina Infinium HumanMethylation850 BeadChip to measure DNA methylation (DNAm) at 866,895 CpGs across the genome. An additional 78 placental samples were utilized to independently validate the array findings by pyrosequencing.ResultsUsing a false discovery rate of < 0.15 and average group difference in DNAm of > 0.05, 66 differentially methylated (DM) CpG sites were identified between aCA cases and non-aCA cases in chorionic villi. For the majority of these 66 DM CpGs, the DNAm profile of the aCA cases as compared to the non-aCA cases trended in the direction of the blood cell DNAm. Interestingly, neutrophil-specific DNAm signatures, but not those associated with other immune cell types, were capable of separating aCA cases from the non-aCA cases.ConclusionsOur results suggest that aCA-associated placentas showed altered DNAm signatures that were not observed in the absence of aCA. This DNAm profile is consistent with the activation of the innate immune response in the placenta and/or reflect increase in neutrophils as a response to inflammation.Electronic supplementary materialThe online version of this article (10.1186/s13072-018-0234-9) contains supplementary material, which is available to authorized users.

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Review: placental biomarkers for assessing fetal health

Cited by 41 publications

References 79 publications

Maternal physical activity-induced adaptive transcriptional response in brain and placenta of mothers and rat offspring

Maternal physical activity-induced adaptive transcriptional response in brain and placenta of mothers and rat offspring

The national blueprint for pregnancy/birth longitudinal cohorts to study factor VIII immunogenicity: NHLBI State of the Science (SOS) Workshop on factor VIII inhibitors

DNA methylation profiling of acute chorioamnionitis-associated placentas and fetal membranes: insights into epigenetic variation in spontaneous preterm births

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