Analysis of mitochondrial regulatory transcripts in publicly available datasets with validation in placentae from pre-term, post-term and fetal growth restriction pregnancies

Bartho, Lucy A.; O’Callaghan, Jessica L.; Fisher, Joshua J.; Cuffe, James; Kaitu’u-Lino, Tu’uhevaha J; Hannan, Natalie J.; Clifton, Vicki L.; Perkins, Anthony V.

doi:10.1016/j.placenta.2021.07.303

Cited by 14 publications

(6 citation statements)

References 44 publications

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“…Additionally, it is reported that SIRT3 affects the migration, invasion, tube formation and necroptosis of trophoblasts and is implicated in the pathogenesis of pre-eclampsia [58]. Furthermore, studies showed that SIRT4 might trigger senescence of trophoblasts [59][60][61]. This evidence further confirms our hypothesis that SIRT1 might participate in the pathogenesis of pre-eclampsia by regulating trophoblastic invasion, migration and proliferation.…”

Section: The Functions Of Other Sirtuins Proteins In Trophoblastssupporting

confidence: 84%

SIRT1: A Novel Protective Molecule in Pre-eclampsia

Liu¹,

Wang²,

Pei³

et al. 2022

Int. J. Med. Sci.

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Pre-eclampsia is a severe pregnant complication, mainly characterized by insufficient trophoblast invasion, impaired uterine spiral artery remodeling, placental hypoxia and ischemia, and endothelial dysfunction. However, the potential mechanisms of pre-eclampsia remain unclear. SIRT1 is a NAD+-dependent deacetylase, involving in multiple biological processes, including energy metabolism, oxidative stress, inflammatory response, and cellular autophagy. Several studies showed that SIRT1 might play a vital role in the pathogenesis of pre-eclampsia. In this review, we aim to integrate the latest research on SIRT1 and pre-eclampsia to explore the comprehensive mechanisms of SIRT1 in pre-eclampsia. More specifically, SIRT1 might affect placental development and trophoblast invasion through autophagy and senescence in pre-eclampsia, and SIRT1 protects vascular endothelial cells from oxidative stress, inflammatory response, autophagy, and senescence. Furthermore, SIRT1 deficiency mice showed typical pre-eclampsia-like performances, which can be reversed via direct SIRT1 supplement or SIRT1 agonist treatment. Additionally, resveratrol, a SIRT1 agonist, attenuates vascular endothelial injury and placental dysfunction, and exerts protective effect on decreasing blood pressure. In this review, we provide new insights into the development of pre-eclampsia, which can establish a theoretical basis for prevention and treatment for pre-eclampsia. Besides, we also propose questions that still need to be further addressed in order to elucidate the comprehensive molecular mechanisms of pre-eclampsia in the future.

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Section: The Functions Of Other Sirtuins Proteins In Trophoblastssupporting

confidence: 84%

SIRT1: A Novel Protective Molecule in Pre-eclampsia

Liu¹,

Wang²,

Pei³

et al. 2022

Int. J. Med. Sci.

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“…6D ). Specifically, we focused on a set of genes that have been reported to be differentially expressed in primary chorionic tissue in the third trimester relative to the first trimester 21 . This previous study reported that expression of the antioxidant genes CLPP , TXNRD2 , HSPD1 and GPX3 was lower in tissue from the third trimester relative to the first trimester; on the other hand, SOD2 , HSPA1A , TRAP1 , TXNRD1 and GDF15 were upregulated in tissue from the third trimester.…”

Section: Resultsmentioning

confidence: 99%

Derivation of human trophoblast stem cells from placentas at birth

Karakis,

Britt,

Jabeen

et al. 2024

Preprint

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Human trophoblast stem cells (hTSCs) have emerged as a powerful tool for modeling the placental cytotrophoblast (CTB) in vitro. hTSCs were originally derived from CTBs of the first trimester placenta or blastocyst-stage embryos in trophoblast stem cell medium (TSCM) that contains epidermal growth factor (EGF), the glycogen synthase kinase-beta (GSK3β) inhibitor CHIR99021, the transforming growth factor-beta (TGFβ) inhibitors A83-01 and SB431542, valproic acid (VPA), and the Rho-associated protein kinase (ROCK) inhibitor Y-27632. Here we show that hTSCs can be derived from CTBs isolated from the term placenta, using TSCM supplemented with a low concentration of mitochondrial pyruvate uptake inhibitor UK5099 and lipid-rich albumin (TUA medium). Notably, hTSCs could not be derived from term CTBs using TSCM alone, or in the absence of either UK5099 or lipid-rich albumin. Strikingly, hTSCs cultured in TUA medium for a few passages could be transitioned into TSCM and cultured thereafter in TSCM. hTSCs from term CTBs cultured in TUA medium as well as those transitioned into and cultured in TSCM thereafter could be differentiated to the extravillous trophoblast and syncytiotrophoblast lineages and exhibited high transcriptome similarity with hTSCs derived from first trimester CTBs. We anticipate that these results will enable facile derivation of hTSCs from normal and pathological placentas at birth with diverse genetic backgrounds and facilitate in vitro mechanistic studies in trophoblast biology.

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“…60 By regulating energy, placental mitochondria are essential to the proper formation and functioning of the organ and a healthy pregnancy. 61 Mitochondria are the major intracellular source and primary target of ROS and, compared with nuclear DNA, mtDNA is more sensitive to oxidative stress due a lack of protective chromatin structure, histones and introns and less efficient repair mechanisms. 62,63 Oxidative stress therefore has the potential to have an adverse effect on placental mitochondria and in doing so impairs the ability of the placenta to support the growing fetus through energy-dependent processes such as active transport and hormone secretion.…”

Section: Oxidative Stressmentioning

confidence: 99%

“…A number of studies have also observed significant associations between increased concentrations of PM 56 – 58 and NO 2 59 during pregnancy and decreased placental/cord blood mtDNA content ( Table 1 ), indicative of mitophagy and mitochondrial death 60 . By regulating energy, placental mitochondria are essential in the proper formation and functioning of the organ and a healthy pregnancy 61 . Mitochondria are the major intracellular source and primary target of ROS and, compared to nuclear DNA, mtDNA is more sensitive to oxidative stress due a lack of protective chromatin structure, histones, and introns and less efficient repair mechanisms 62 , 63 .…”

Section: Mechanisms Underlying Adverse Birth Outcomesmentioning

confidence: 99%

Ambient air pollution and adverse birth outcomes: A review of underlying mechanisms

Fussell,

Jauniaux,

Smith

et al. 2023

BJOG

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Epidemiological data provide varying degrees of evidence for associations between prenatal exposure to ambient air pollutants and adverse birth outcomes (suboptimal measures of fetal growth, preterm birth and stillbirth). To assess further certainty of effects, this review examines the experimental literature base to identify mechanisms by which air pollution (particulate matter, nitrogen dioxide and ozone) could cause adverse effects on the developing fetus. It likely that this environmental insult impacts multiple biological pathways important for sustaining a healthy pregnancy, depending upon the composition of the pollutant mixture and the exposure window owing to changes in physiologic maturity of the placenta, its circulations and the fetus as pregnancy ensues. The current body of evidence indicates that the placenta is a target tissue, impacted by a variety of critical processes including nitrosative/oxidative stress, inflammation, endocrine disruption, epigenetic changes, as well as vascular dysregulation of the maternal‐fetal unit. All of the above can disturb placental function and, as a consequence, could contribute to compromised fetal growth as well increasing the risk of stillbirth. Furthermore, given that there is often an increased inflammatory response associated with preterm labour, inflammation is a plausible mechanism mediating the effects of air pollution on premature delivery. In the light of increased urbanisation and an ever‐changing climate, both of which increase ambient air pollution and negatively affect vulnerable populations such as pregnant individuals, it is hoped that the collective evidence may contribute to decisions taken to strengthen air quality policies, reductions in exposure to air pollution and subsequent improvements in the health of those not yet born.

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Analysis of mitochondrial regulatory transcripts in publicly available datasets with validation in placentae from pre-term, post-term and fetal growth restriction pregnancies

Cited by 14 publications

References 44 publications

SIRT1: A Novel Protective Molecule in Pre-eclampsia

SIRT1: A Novel Protective Molecule in Pre-eclampsia

Derivation of human trophoblast stem cells from placentas at birth

Ambient air pollution and adverse birth outcomes: A review of underlying mechanisms

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