Tracking placental development in health and disease

Aplin, John D.; Myers, Jenny; Timms, Kate; Westwood, Melissa

doi:10.1038/s41574-020-0372-6

Cited by 215 publications

(180 citation statements)

References 208 publications

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“…Decidual transformation of human endometrium upon embryo implantation requires differentiation of resident EnSC, immune clearance of acute senescent decidual cells, and rapid tissue growth. These processes occur in concert with coordinated trophoblast invasion [53]. Considering the magnitude of tissue remodeling required for pregnancy, poised progenitor and highly proliferative decidual precursor cells are likely critical for the formation of a robust maternal-fetal interface, as is the case in mice [20].…”

Section: Discussionmentioning

confidence: 99%

Characterization of highly proliferative decidual precursor cells during the window of implantation in human endometrium

Diniz-da-Costa

Kong

Fishwick

et al. 2020

Preprint

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Pregnancy depends on the wholesale transformation of the endometrium, a process driven by differentiation of endometrial stromal cells (EnSC) into specialist decidual cells. Upon embryo implantation, decidual cells impart the tissue plasticity needed to accommodate a rapidly growing conceptus and invading placenta, although the underlying mechanisms are unclear. Here we characterize a discrete population of highly proliferative mesenchymal cells (hPMC) in midluteal human endometrium, coinciding with the window of embryo implantation. Single-cell transcriptomics demonstrated that hPMC express genes involved in chemotaxis and vascular transmigration. Although distinct from resident EnSC, hPMC also express genes encoding pivotal decidual transcription factors and markers, most prominently prolactin. We further show that hPMC are enriched around spiral arterioles, scattered throughout the stroma, and occasionally present in glandular and luminal epithelium. The abundance of hPMC correlated with the in vitro colony-forming unit activity of midluteal endometrium and, conversely, clonogenic cells in culture express a gene signature partially conserved in hPMC. Cross-referencing of single-cell RNA-sequencing data sets indicated that hPMC differentiate into a recently discovered decidual subpopulation in early pregnancy. Finally, we demonstrate that recurrent pregnancy loss is associated with hPMC depletion. Collectively, our findings characterize midluteal hPMC as novel decidual precursors that are likely derived from circulating bone marrow-derived mesenchymal stem/stromal cells and integral to decidual plasticity in pregnancy.

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Section: Discussionmentioning

confidence: 99%

Characterization of highly proliferative decidual precursor cells during the window of implantation in human endometrium

Diniz-da-Costa

Kong

Fishwick

et al. 2020

Preprint

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“…Failure of this process is likely behind many of the recurrent implantation failures seen in assisted reproduction patients and may also contribute to cases of recurrent miscarriage (Koot et al 2011). Furthermore, there is increasing awareness that later stage obstetric pathologies have their origin in implantation and early pregnancy (Rabaglino et al 2015, Garrido-Gomez et al 2017, Than et al 2018, Aplin et al 2020, and understanding endometrial shaping of trophoblast development is central to developing new treatments.…”

Section: Discussionmentioning

confidence: 99%

Trophectoderm differentiation to invasive syncytiotrophoblast is induced by endometrial epithelial cells during human embryo implantation

Ruane¹,

Garner²,

Parsons

et al. 2020

Preprint

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At implantation, trophoblast derived from the trophectoderm of the blastocyst-stage embryo invades the endometrium to establish pregnancy. To understand how embryos breach the endometrial epithelium, we modelled human implantation using blastocysts or trophoblast stem cell spheroids cultured with endometrial epithelial cells (EEC). Blastocyst invasion of the EEC layer was initiated by multinuclear syncytiotrophoblast. Spheroids also invaded the epithelium with syncytiotrophoblast, and EEC induced upregulation of syncytiotrophoblast markers. Modelling implantation in silico using blastocyst and EEC transcriptomes revealed gene networks that exhibited greater connectivity and organisation in trophectoderm of the polar region of the embryonic axis. However, gene ontologies and machine learning suggested that EEC drives syncytiotrophoblast differentiation in polar and mural trophectoderm. This is the first evidence for endometrial epithelium-induced trophectoderm differentiation to invasive syncytiotrophoblast as the cellular mechanism of embryonic breaching of the endometrium in humans, with implications for reproductive medicine and our understanding of human embryonic development.

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“…Maternal endothelial dysfunction caused by placental factors (pro- and anti-angiogenic proteins) has long been considered one of the pathophysiological factors underlying severe pre-eclampsia ( Roberts and Hubel, 2009 ). However, whether angiomodulatory imbalance is a consequence of an underlying pathology that is common to several different types of placental dysfunction is still unclear, as is whether it reflects a specific abnormality of earlier placental development ( Aplin et al, 2020 ). There is now sufficient evidence to suggest that tissue-specific of LNs and their associated signaling regulates cell behavior and angiogenesis [as reviewed in Simon-Assmann et al (2011) ].…”

Section: Laminins and Pre-eclampsiamentioning

confidence: 99%

“…During a normal pregnancy, placentation begins with the recognition and adhesion of the trophectoderm to the uterine epithelium; trophoblast stem cells originate from the embryonic trophectoderm and differentiate into various trophoblast lineages [as reviewed in Silva and Serakides (2016)]. A recent review (Aplin et al, 2020) clearly summarized the steps in normal and failed uterine spiral arterial conversion. Cytotrophoblast cells invade into the decidua (interstitial trophoblast), and then the wall of maternal uterine spiral artery is destroyed, including the endothelium and smooth muscle cell.…”

Section: Introductionmentioning

confidence: 99%

Laminins Regulate Placentation and Pre-eclampsia: Focus on Trophoblasts and Endothelial Cells

Liu

Yin

et al. 2020

Front. Cell Dev. Biol.

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Pre-eclampsia is a systemic vascular disease characterized by new-onset hypertension and/or proteinuria at ≥20 weeks of gestation and leads to high rates of maternal and perinatal morbidity and mortality. Despite the incomplete understanding of pre-eclampsia pathophysiology, it is accepted that insufficient spiral artery remodeling and endothelial dysfunction are major contributors. Laminins (LNs) are a vital family of extracellular matrix (ECM) molecules present in basement membranes that provide unique spatial and molecular information to regulate implantation and placentation. LNs interact with cell surface receptors to trigger intracellular signals that affect cellular behavior. This mini-review summarizes the role of LNs in placental development during normal pregnancy. Moreover, it describes how LN deficiency can lead to the pre-eclampsia, which is associated with trophoblast and vascular endothelial dysfunction. New research directions and the prospect of clinical diagnosis of LN deficiency are discussed, and the gaps in basic and clinical research in this field are highlighted.

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Tracking placental development in health and disease

Cited by 215 publications

References 208 publications

Characterization of highly proliferative decidual precursor cells during the window of implantation in human endometrium

Characterization of highly proliferative decidual precursor cells during the window of implantation in human endometrium

Trophectoderm differentiation to invasive syncytiotrophoblast is induced by endometrial epithelial cells during human embryo implantation

Laminins Regulate Placentation and Pre-eclampsia: Focus on Trophoblasts and Endothelial Cells

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