Placental transcriptional and histologic subtypes of normotensive fetal growth restriction are comparable to preeclampsia

Gibbs, Isaac; Leavey, Katherine; Benton, Samantha J.; Grynspan, David; Bainbridge, Shannon; Cox, Brian

doi:10.1016/j.ajog.2018.10.003

Cited by 42 publications

(38 citation statements)

References 86 publications

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“…Attempts have been made to delineate pre-eclampsia from other complications, such as gestational diabetes mellitus (GDM), intrauterine growth restriction (IUGR) and macrosomia ( Sitras et al , 2009a ; Mayor-Lynn et al , 2011 ; Nishizawa et al , 2011 ; Guo et al , 2013 ; Sober et al , 2015 ; Lekva et al , 2016 ; Gibbs et al , 2019 ). Results of these studies are consistent with the notion that pre-eclampsia is heterogeneous, comprising of multiple molecular subtypes that distinctly cluster with other pregnancy pathologies ( Guo et al , 2013 ; Gibbs et al , 2019 ), suggestive of a shared aetiology or pathophysiology involving the placenta ( Nishizawa et al , 2011 ; Sober et al , 2015 ).…”

Section: Placental Transcriptome Studies Of Pregnancy Complicationsmentioning

confidence: 99%

“…This review considers 17 datasets representing a total of 721 placentas of which 26% were either from SGA- or IUGR-affected pregnancies ( Table II: IUGR/SGA). Most placental transcriptome studies utilized only the criterion of SGA ( McCarthy et al , 2007 ; Sabri et al , 2014 ; Sober et al , 2015 ; Deyssenroth et al , 2017 ; Verheecke et al , 2018 ; Gibbs et al , 2019 ), while some studies excluded those who may be healthy and constitutionally small, by including an additional criterion of a small abdominal circumference below the fifth centile ( Guo et al , 2013 ; Madeleneau et al , 2015 ) or ultrasound findings of abnormal uteroplacental blood flow indicative of placental insufficiency ( Roh et al , 2005 ; Sitras et al , 2009a ; Struwe et al , 2010 ; Nishizawa et al , 2011 ; Dunk et al , 2012 ; Majewska et al , 2019 ). However, while some of these IUGR cases may be explained by maternal smoking, pre-eclampsia or chemotherapy during pregnancy ( Sitras et al , 2009a ; Dunk et al , 2012 ; Verheecke et al , 2018 ), a considerable number of cases have no specific identifiable underlying cause and are termed idiopathic ( Nishizawa et al , 2011 ).…”

Section: Placental Transcriptome Studies Of Pregnancy Complicationsmentioning

confidence: 99%

“…Dysregulated expression of genes involved in the processes of placental growth signalling, mitochondrial respiration and a hypoxic response was observed in multiple IUGR studies ( Roh et al , 2005 ; McCarthy et al , 2007 ; Struwe et al , 2010 ; Guo et al , 2013 ; Sabri et al , 2014 ; Madeleneau et al , 2015 ; Deyssenroth et al , 2017 ; Verheecke et al , 2018 ). Several studies also demonstrated a substantial overlap between pre-eclampsia and normotensive growth restriction, encompassing genes involved in the molecular processes of placental angiogenesis and immune regulation ( Sitras et al , 2009a ; Nishizawa et al , 2011 ; Dunk et al , 2012 ; Guo et al , 2013 ; Sober et al , 2015 ; Gibbs et al , 2019 ; Majewska et al , 2019 ). Additional research to increase understanding of placental function in growth-compromised pregnancies could improve diagnosis and management of cases.…”

Section: Placental Transcriptome Studies Of Pregnancy Complicationsmentioning

confidence: 99%

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Current approaches and developments in transcript profiling of the human placenta

Yong

Chan

2020

Human Reproduction Update

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BACKGROUND The placenta is the active interface between mother and foetus, bearing the molecular marks of rapid development and exposures in utero. The placenta is routinely discarded at delivery, providing a valuable resource to explore maternal-offspring health and disease in pregnancy. Genome-wide profiling of the human placental transcriptome provides an unbiased approach to study normal maternal–placental–foetal physiology and pathologies. OBJECTIVE AND RATIONALE To date, many studies have examined the human placental transcriptome, but often within a narrow focus. This review aims to provide a comprehensive overview of human placental transcriptome studies, encompassing those from the cellular to tissue levels and contextualize current findings from a broader perspective. We have consolidated studies into overarching themes, summarized key research findings and addressed important considerations in study design, as a means to promote wider data sharing and support larger meta-analysis of already available data and greater collaboration between researchers in order to fully capitalize on the potential of transcript profiling in future studies. SEARCH METHODS The PubMed database, National Center for Biotechnology Information and European Bioinformatics Institute dataset repositories were searched, to identify all relevant human studies using ‘placenta’, ‘decidua’, ‘trophoblast’, ‘transcriptome’, ‘microarray’ and ‘RNA sequencing’ as search terms until May 2019. Additional studies were found from bibliographies of identified studies. OUTCOMES The 179 identified studies were classifiable into four broad themes: healthy placental development, pregnancy complications, exposures during pregnancy and in vitro placental cultures. The median sample size was 13 (interquartile range 8–29). Transcriptome studies prior to 2015 were predominantly performed using microarrays, while RNA sequencing became the preferred choice in more recent studies. Development of fluidics technology, combined with RNA sequencing, has enabled transcript profiles to be generated of single cells throughout pregnancy, in contrast to previous studies relying on isolated cells. There are several key study aspects, such as sample selection criteria, sample processing and data analysis methods that may represent pitfalls and limitations, which need to be carefully considered as they influence interpretation of findings and conclusions. Furthermore, several areas of growing importance, such as maternal mental health and maternal obesity are understudied and the profiling of placentas from these conditions should be prioritized. WIDER IMPLICATIONS Integrative analysis of placental transcriptomics with other ‘omics’ (methylome, proteome and metabolome) and linkage with future outcomes from longitudinal studies is crucial in enhancing knowledge of healthy placental development and function, and in enabling the underlying causal mechanisms of pregnancy complications to be identified. Such understanding could help in predicting risk of future adversity and in designing interventions that can improve the health outcomes of both mothers and their offspring. Wider collaboration and sharing of placental transcriptome data, overcoming the challenges in obtaining sufficient numbers of quality samples with well-defined clinical characteristics, and dedication of resources to understudied areas of pregnancy will undoubtedly help drive the field forward.

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Section: Placental Transcriptome Studies Of Pregnancy Complicationsmentioning

confidence: 99%

Section: Placental Transcriptome Studies Of Pregnancy Complicationsmentioning

confidence: 99%

Section: Placental Transcriptome Studies Of Pregnancy Complicationsmentioning

confidence: 99%

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Current approaches and developments in transcript profiling of the human placenta

Yong

Chan

2020

Human Reproduction Update

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“…Both PE and FGR are often associated with a small placenta at delivery, and show various combinations of villous hypermaturity, infarction, and decidual vasculopathy, on histopathologic examination [1,2]. Recent studies have used a combination of gene expression profiling and histopathology to further separate PE and FGR into unique subtypes, with the potential to identify biomarkers with improved diagnostic accuracy [20][21][22][23]. However, trophoblast lineage-specific differentiation has yet to be described in these different disease subtypes.…”

Section: Preeclampsia and Fetal Growth Restriction: Clinical Synopsismentioning

confidence: 99%

“…However, results of studies evaluating CTB proliferation in PE/FGR range from no differences in CTB proliferation [50,51], region-specific alterations in CTB proliferation [52], to an increase in CTB proliferation attributed to a damaged syncytium in need of repair and regeneration [53,54]. Given the heterogeneity of PE and FGR, as recently elaborated on by genome-wide expression profiling of placental tissues associated with these complications [20][21][22][23], it is possible that distinct subclasses of these diseases have different alterations at the cellular level, including differences in CTB proliferation, depending on the underlying pathophysiology.…”

Section: Abnormalities Of Villous Trophoblast Associated With Pe/fgrmentioning

confidence: 99%

Trophoblast lineage-specific differentiation and associated alterations in preeclampsia and fetal growth restriction

et al. 2020

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The human placenta is a poorly-understood organ, but one that is critical for proper development and growth of the fetus in-utero. The epithelial cell type that contributes to primary placental functions is called "trophoblast," including two main subtypes, villous and extravillous trophoblast. Cytotrophoblast and syncytiotrophoblast comprise the villous compartment and contribute to gas and nutrient exchange, while extravillous trophoblast invade and remodel the uterine wall and vessels, in order to supply maternal blood to the growing fetus. Abnormal differentiation of trophoblast contributes to placental dysfunction and is associated with complications of pregnancy, including preeclampsia (PE) and fetal growth restriction (FGR). This review describes what is known about the cellular organization of the placenta during both normal development and in the setting of PE/FGR. It also explains known trophoblast lineagespecific markers and pathways regulating their differentiation, and how these are altered in the setting of PE/FGR, focusing on studies which have used human placental tissues. Finally, it also highlights remaining questions and needed resources to advance this field.

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Innovations in Placental Pathology

Pantham

Soncin

Zhang-Rutledge

et al. 2021

Benirschke's Pathology of the Human Placenta

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Placental transcriptional and histologic subtypes of normotensive fetal growth restriction are comparable to preeclampsia

Cited by 42 publications

References 86 publications

Current approaches and developments in transcript profiling of the human placenta

Current approaches and developments in transcript profiling of the human placenta

Trophoblast lineage-specific differentiation and associated alterations in preeclampsia and fetal growth restriction

Innovations in Placental Pathology

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