The Role of Epigenetics in Placental Development and the Etiology of Preeclampsia

Apicella, Clara; Ruano, Camino S. M.; Méhats, Céline; Miralles, Francisco; Vaiman, Daniel

doi:10.3390/ijms20112837

Cited by 137 publications

(105 citation statements)

References 323 publications

(347 reference statements)

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“…A variety of lncRNAs including H19, MALAT-1, MEG3, RNA-ATB. PVT1, TUG1, and DIAPH2-AS1 involved in preeclampsia and were discussed in detail and in-depth (Apicella et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

Long Non-coding RNA Gas5 Is Associated With Preeclampsia and Regulates Biological Behaviors of Trophoblast via MicroRNA-21

Zheng

Hou

et al. 2020

Front. Genet.

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Preeclampsia is a lethal pregnancy specific hypertensive disorder involving multisystem. Despite extensive studies to investigate the causes of preeclampsia, the pathogenesis still remains largely unknown. Long non-coding RNAs (lncRNAs) are a diverse class of non-translated RNAs which play a crucial part in various biological phenomena. Although lncRNA Growth Arrest-Specific 5 (GAS5) aberrantly expressed in multiple cancer tissues and is implicated in multiple biological processes of tumor cells, little is known about its role in preeclampsia. In this study, 40 patients with preeclampsia and 32 gestational age matched normotension pregnant women were recruited. Using quantitative real-time polymerase chain reaction (qRT-PCR), we found higher expression of GAS5 in placenta of preclamsia affected women. The level of GAS5 existed strongly in correlation with Thrombin Time indicating coagulation function and other clinical parameters by Pearson correlation analysis. Then we constructed the GAS5 lentivirus expression vectors and transfected into human trophoblast cell lines HTR-8/SVneo and JEG-3. Using in vitro cell culture studies, we found an inhibited effect of GAS5 on proliferative ability, migratory ability and invasive ability however; no effect on apoptosis was detected. Further mechanistic analysis found that GAS5 modulated microRNA-21 (miR-21) in an opposite variation tendency by qRT-PCR and rescue experiment. In addition, inhibition of GAS5 promoted the activation of PI3K/AKT signaling pathway and its downstream proteins covering MMP-9 and TP53 as evident from our qRT-PCR and western blot analyses. Thus, we suggested that GAS5 might involve in pregnancy with preeclampsia by influencing the biological functions of trophoblast cells through the regulation of miR-21 and activation of PI3K/AKT signaling pathway and its downstream targets, which may contribute to reveal the nature of preeclampsia.

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“…A variety of lncRNAs including H19, MALAT-1, MEG3, RNA-ATB. PVT1, TUG1, and DIAPH2-AS1 involved in preeclampsia and were discussed in detail and in-depth (Apicella et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

Long Non-coding RNA Gas5 Is Associated With Preeclampsia and Regulates Biological Behaviors of Trophoblast via MicroRNA-21

Zheng

Hou

et al. 2020

Front. Genet.

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“…Epigenetic alterations have also been noted in preeclampsia including alterations of methylation in the placenta of pre-eclamptic patients. Additionally, it is hypothesized that antiangiogenic and cytotoxic factors released by the placenta in preeclampsia have the potential to induce epigenetic modifications in maternal tissues (132).…”

Section: Current Understanding Of Pre-eclampsiamentioning

confidence: 99%

Immunological Role of the Maternal Uterine Microbiome in Pregnancy: Pregnancies Pathologies and Alterated Microbiota

et al. 2020

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Understanding what happens at the time of embryo implantation has been the subject of significant research. Investigators from many differing fields including maternal fetal medicine, microbiology, genetics, reproductive endocrinology and immunology have all been studying the moment the embryo interacts with the maternal endometrium. A perfect relationship between the uterus and the embryo, mediated by a tightly controlled interaction between the embryo and the endometrium, is required for successful implantation. Any factors affecting this communication, such as altered microbiome may lead to poor reproductive outcomes. Current theories suggest that altered microbiota may trigger an inflammatory response in the endometrium that affects the success of embryo implantation, as inflammatory mediators are tightly regulated during the adhesion of the blastocyst to the epithelial endometrial wall. In this review, we will highlight the various microbiome found during the periconceptual period, the microbiomes interaction with immunological responses surrounding the time of implantation, its effect on implantation, placentation and ultimately maternal and neonatal outcomes.

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“…These include peptide and steroid hormones, structural and immune proteins, enzymes, and transcription factors. [14][15][16][17]19] Remarkably, separate observations have noted that many predominantly placenta-expressed (PPE) molecules are encoded by primate-specific gene clusters (e.g., chorionic gonadotropins (CGBs), galectins, microRNAs) [15][16][17][19][20][21][22][23][24][25][26], suggesting that the evolution of these clusters and their trophoblastic expression might have strongly impacted the complex regulation of pregnancy in humans.…”

Section: Introductionmentioning

confidence: 99%

Placenta-Specific Genes, Their Regulation During Villous Trophoblast Differentiation and Dysregulation in Preterm Preeclampsia

Szilágyi

Gelencser

Romero

et al. 2020

IJMS

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The human placenta maintains pregnancy and supports the developing fetus by providing nutrition, gas-waste exchange, hormonal regulation, and an immunological barrier from the maternal immune system. The villous syncytiotrophoblast carries most of these functions and provides the interface between the maternal and fetal circulatory systems. The syncytiotrophoblast is generated by the biochemical and morphological differentiation of underlying cytotrophoblast progenitor cells. The dysfunction of the villous trophoblast development is implicated in placenta-mediated pregnancy complications. Herein, we describe gene modules and clusters involved in the dynamic differentiation Int.Int. J. Mol. Sci. 2020, 21, 628 2 of 27 of villous cytotrophoblasts into the syncytiotrophoblast. During this process, the immune defense functions are first established, followed by structural and metabolic changes, and then by peptide hormone synthesis. We describe key transcription regulatory molecules that regulate gene modules involved in placental functions. Based on transcriptomic evidence, we infer how villous trophoblast differentiation and functions are dysregulated in preterm preeclampsia, a life-threatening placenta-mediated obstetrical syndrome for the mother and fetus. In the conclusion, we uncover the blueprint for villous trophoblast development and its impairment in preterm preeclampsia, which may aid in the future development of non-invasive biomarkers for placental functions and early identification of women at risk for preterm preeclampsia as well as other placenta-mediated pregnancy complications.

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The Role of Epigenetics in Placental Development and the Etiology of Preeclampsia

Cited by 137 publications

References 323 publications

Long Non-coding RNA Gas5 Is Associated With Preeclampsia and Regulates Biological Behaviors of Trophoblast via MicroRNA-21

Long Non-coding RNA Gas5 Is Associated With Preeclampsia and Regulates Biological Behaviors of Trophoblast via MicroRNA-21

Immunological Role of the Maternal Uterine Microbiome in Pregnancy: Pregnancies Pathologies and Alterated Microbiota

Placenta-Specific Genes, Their Regulation During Villous Trophoblast Differentiation and Dysregulation in Preterm Preeclampsia

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