Increased apoptosis in the syncytiotrophoblast in human term placentas complicated by either preeclampsia or intrauterine growth retardation

Ishihara, Naonori; Matsuo, Hiroya; Murakoshi, Homare; Laoag-Fernandez, Jovelle B.; Samoto, Takashi; Maruo, Takeshi

doi:10.1067/mob.2002.119176

Cited by 469 publications

(307 citation statements)

References 22 publications

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“…These results suggested that EVTB in early preeclamptic placentas might have higher levels of cell death. This conclusion is in line with previous reports that trophoblastic apoptosis is increased in PE (52)(53)(54)(55)(56)(57)(58)(59). Despite the invasion insufficiency of EVTB in PE, the increased cell death in EVTB may also contribute to the up-regulation of the EVTB signatures in the maternal plasma of early preeclamptic patients.…”

Section: Deciphering Cellular Aberrations In Preeclamptic Placentas Fromsupporting

confidence: 82%

Integrative single-cell and cell-free plasma RNA transcriptomics elucidates placental cellular dynamics

Tsang

Vong

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

264

267

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The human placenta is a dynamic and heterogeneous organ critical in the establishment of the fetomaternal interface and the maintenance of gestational well-being. It is also the major source of cell-free fetal nucleic acids in the maternal circulation. Placental dysfunction contributes to significant complications, such as preeclampsia, a potentially lethal hypertensive disorder during pregnancy. Previous studies have identified significant changes in the expression profiles of preeclamptic placentas using whole-tissue analysis. Moreover, studies have shown increased levels of targeted RNA transcripts, overall and placental contributions in maternal cell-free nucleic acids during pregnancy progression and gestational complications, but it remains infeasible to noninvasively delineate placental cellular dynamics and dysfunction at the cellular level using maternal cell-free nucleic acid analysis. In this study, we addressed this issue by first dissecting the cellular heterogeneity of the human placenta and defined individual cell-type-specific gene signatures by analyzing more than 24,000 nonmarker selected cells from full-term and early preeclamptic placentas using large-scale microfluidic single-cell transcriptomic technology. Our dataset identified diverse cellular subtypes in the human placenta and enabled reconstruction of the trophoblast differentiation trajectory. Through integrative analysis with maternal plasma cell-free RNA, we resolved the longitudinal cellular dynamics of hematopoietic and placental cells in pregnancy progression. Furthermore, we were able to noninvasively uncover the cellular dysfunction of extravillous trophoblasts in early preeclamptic placentas. Our work showed the potential of integrating transcriptomic information derived from single cells into the interpretation of cell-free plasma RNA, enabling the noninvasive elucidation of cellular dynamics in complex pathological conditions. single-cell transcriptomics | cell-free RNA | noninvasive prenatal testing | placenta | preeclampsia

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Section: Deciphering Cellular Aberrations In Preeclamptic Placentas Fromsupporting

confidence: 82%

Integrative single-cell and cell-free plasma RNA transcriptomics elucidates placental cellular dynamics

Tsang

Vong

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

264

267

View full text Add to dashboard Cite

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“…This issue is important, because the biological effects of necrotic or apoptotic trophoblast debris may be different. Increased apoptosis of villous trophoblast noted in the placentae of women with pre-eclampsia suggests a role for apoptosis 28,29 . Moreover, increased apoptosis of extravillous trophoblast in pre-eclampsia has also been observed 26,27 .…”

Section: Discussionmentioning

confidence: 99%

“…Recently, increased apoptosis of the extravillous trophoblast in the placental bed 26,27 and villous trophoblast 28,29 have been reported in pre-eclampsia and implicated as a mechanism of disease in the pathophysiology of the disorder. A high rate of apoptosis in villous trophoblast may lead to deportation of trophoblast cells into the maternal circulation, while the increased cell death may explain defective trophoblast invasion of the decidua and spiral arteries (abnormal placentation), as well as activation of the hemostatic system in patients with preeclampsia 26,[36][37][38] .…”

Section: Introductionmentioning

confidence: 99%

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Maternal serum of women with pre-eclampsia reduces trophoblast cell viability: evidence for an increased sensitivity to Fas-mediated apoptosis

Neale

Demasio

Illuzi

et al. 2003

The Journal of Maternal-Fetal & Neonatal Medicine

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“…Since apoptosis increases in the placenta with gestational age (16,17) or due to elevated levels of TNF-␣ at the maternal-fetal interface, we postulate that XAF1 is demethylated, resulting in the induction of XAF1 expression and an increase in trophoblast apoptosis. Current studies are aimed at determining whether XAF1 is unmethylated in placentas from complicated pregnancies, such as preeclampsia, intrauterine growth restriction (IUGR) and preterm labor, which are characterized by a greater incidence of trophoblast apoptosis (47)(48)(49)(50)(51)(52).…”

Section: Discussionmentioning

confidence: 99%

XAF1 Mediates Tumor Necrosis Factor-α-induced Apoptosis and X-linked Inhibitor of Apoptosis Cleavage by Acting through the Mitochondrial Pathway

Chavez

Visintin

Karassina

et al. 2007

Journal of Biological Chemistry

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Tumor necrosis factor-␣ (TNF-␣) and Fas ligand induce apoptosis by interacting with their corresponding membranebound death receptors and activating caspases. Since both systems share several components of the intracellular apoptotic cascade and are expressed by first trimester trophoblasts, it is unknown how these cells remain resistant to Fas ligand while sensitive to TNF-␣. XAF1 (X-linked inhibitor of apoptosis (XIAP)-associated factor 1) is a proapoptotic protein that antagonizes the caspase-inhibitory activity of XIAP. Here, we demonstrated that XAF1 functions as an alternative pathway for TNF-␣-induced apoptosis by translocating to the mitochondria and promoting XIAP inactivation. In addition, we showed that the overexpression of XAF1 sensitized first trimester trophoblast cells to Fas-mediated apoptosis. Furthermore, we also determined that the differential expression of XAF1 in first and third trimester trophoblast cells was due to changes in XAF1 gene methylation. Our results establish a novel regulatory pathway controlling trophoblast cell survival and provide a molecular mechanism to explain trophoblast sensitivity to TNF-␣ and the increased number of apoptotic trophoblast cells observed near term. Aberrant XAF1 expression and/or localization may have consequences for normal pregnancy outcome.

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Increased apoptosis in the syncytiotrophoblast in human term placentas complicated by either preeclampsia or intrauterine growth retardation

Cited by 469 publications

References 22 publications

Integrative single-cell and cell-free plasma RNA transcriptomics elucidates placental cellular dynamics

Integrative single-cell and cell-free plasma RNA transcriptomics elucidates placental cellular dynamics

Maternal serum of women with pre-eclampsia reduces trophoblast cell viability: evidence for an increased sensitivity to Fas-mediated apoptosis

XAF1 Mediates Tumor Necrosis Factor-α-induced Apoptosis and X-linked Inhibitor of Apoptosis Cleavage by Acting through the Mitochondrial Pathway

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