Study of mitochondrial function in placental insufficiency

Lefebvre, Tiphaine; Roche, Ombeline; Seegers, Valérie; Cherif, Majida; Khiati, Salim; Guéguen, Naïg; Desquiret-Dumas, Valérie; Geffroy, Guillaume; Blanchet, Odile; Reynier, Pascal; Legendre, Guillaume; Lenaers, Guy; Procaccio, Vincent; Gascoin, Géraldine

doi:10.1016/j.placenta.2018.05.007

Cited by 12 publications

(5 citation statements)

References 25 publications

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“…Notably, the significant alteration in ATP6 observed in pigs with IUGR lends support to our results (Luo et al 2018). Additionally, our observations align with previously published reports in humans, where investigations demonstrated abnormalities in mitochondrial structure and perturbations in molecular pathways regulating mitochondrial content and function within the placenta under the conditions of IUGR and preeclampsia (Lefebvre et al 2018;Vangrieken et al 2021). These collective findings underscore the significance of mitochondrial dysfunction in the context of RP, shedding light on potential connections and shared pathways across species and reproductive complications.…”

Section: Discussionsupporting

confidence: 92%

Mitochondrial Bioenergetics in Placenta of Crossbred Cattle- Deciphering the Association of Mitochondrial Alterations with Retained Placenta

S. Lahamge,

E.M

2024

Preprint

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Retention of placenta (RP) in crossbred cattle poses health, reproductive, and economic challenges linked to oxidative stress, hormonal imbalances, and complex causative factors. Emphasizing the key role of mitochondria in oxidative phosphorylation (OXPHOS) and hormone synthesis, our study is the first to explore differences in OXPHOS activity, mitochondrial content, and mtDNA-encoded gene expression between normal and RP. In addition, gross morphological examination of placental tissues from both groups revealed noticeable disparities in cotyledons of RP as compared to normal placenta. Moreover, OXPHOS complex I specific activity was decreased in RP, and RT-qPCR analysis unveiled a significant reduction in transcript levels of 10 mtDNA-encoded protein genes. While COX3 and ATP8 genes showed no significant changes, ND6 increased in RP. Whereas, mtDNA copy number varied between animals but showed no statistically significant differences among groups. Retained placenta manifests alterations in the transcript levels of various mitochondrial genes, complex activity, and mtDNA content, potentially linked to heightened energy demands or mitochondrial insufficiency, posing an elevated risk. Overall, our study suggests a link between mitochondrial abnormalities, gene expression, and RP. This connection could influence the removal of fetal membranes by affecting energy supply, hormonal balance, and oxidative stress. This study also offers novel insights and serves as a valuable animal model for studying placental insufficiency in humans. Moving forward, comprehensive investigations are imperative to unravel underlying mechanisms and intricate roles of mitochondria in the context of RP, paving the way for targeted interventions to mitigate health, reproductive, and economic challenges in crossbred cattle.

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Section: Discussionsupporting

confidence: 92%

Mitochondrial Bioenergetics in Placenta of Crossbred Cattle- Deciphering the Association of Mitochondrial Alterations with Retained Placenta

S. Lahamge,

E.M

2024

Preprint

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“…Similarly, we found no differences in lipid peroxidation, as an indicator of oxidative stress, between groups, in any tissue. Previous studies in IUGR reported controversial results in oxidative damage but in other pregnancy complications caused by placental insufficiency, such as preeclampsia, it is described an induction of oxidative stress in the placenta and maternal blood, as well as in certain risk pregnancies depending on the type of delivery (specially vaginal delivery because of intermittent perfusion of intervillous space of the placenta during uterine contractions) . In our cohort of IUGR pregnancies, we reduced preeclampsia comorbidity and vaginal delivery to avoid potential confounders.…”

Section: Discussionmentioning

confidence: 99%

Mitochondrial implications in human pregnancies with intrauterine growth restriction and associated cardiac remodelling

Guitart‐Mampel

Juárez‐Flores

Youssef

et al. 2019

J Cellular Molecular Medi

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Intrauterine growth restriction (IUGR) is an obstetric complication characterised by placental insufficiency and secondary cardiovascular remodelling that can lead to cardiomyopathy in adulthood. Despite its aetiology and potential therapeutics are poorly understood, bioenergetic deficits have been demonstrated in adverse foetal and cardiac development. We aimed to evaluate the role of mitochondria in human pregnancies with IUGR. In a single‐site, cross‐sectional and observational study, we included placenta and maternal peripheral and neonatal cord blood mononuclear cells (PBMC and CBMC) from 14 IUGR and 22 control pregnancies. The following mitochondrial measurements were assessed: enzymatic activities of mitochondrial respiratory chain (MRC) complexes I, II, IV, I + III and II + III, oxygen consumption (cell and complex I‐stimulated respiration), mitochondrial content (citrate synthase [CS] activity and mitochondrial DNA copy number), total ATP levels and lipid peroxidation. Sirtuin3 expression was evaluated as a potential regulator of bioenergetic imbalance. Intrauterine growth restriction placental tissue showed a significant decrease of MRC CI enzymatic activity ( P < 0.05) and CI‐stimulated oxygen consumption ( P < 0.05) accompanied by a significant increase of Sirtuin3/β‐actin protein levels ( P < 0.05). Maternal PBMC and neonatal CBMC from IUGR patients presented a not significant decrease in oxygen consumption (cell and CI‐stimulated respiration) and MRC enzymatic activities (CII and CIV). Moreover, CS activity was significantly reduced in IUGR new‐borns ( P < 0.05). Total ATP levels and lipid peroxidation were preserved in all the studied tissues. Altered mitochondrial function of IUGR is especially present at placental and neonatal level, conveying potential targets to modulate obstetric outcome through dietary interventions aimed to regulate Sirtuin3 function.

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“…All placental tissues were dissected within 30 min after delivery. The protocol for placental dissection has been described previously [ 15 ]. Briefly, after removal of maternal decidua and amniotic membranes, 1 cm 3 sections of placental villi were dissected from four different cotyledons between the basal and chorionic plates.…”

Section: Methodsmentioning

confidence: 99%

A Metabolomic Profiling of Intra-Uterine Growth Restriction in Placenta and Cord Blood Points to an Impairment of Lipid and Energetic Metabolism

et al. 2022

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(1) Background: Intrauterine growth restriction (IUGR) involves metabolic changes that may be responsible for an increased risk of metabolic and cardiovascular diseases in adulthood. Several metabolomic profiles have been reported in maternal blood and urine, amniotic fluid, cord blood and newborn urine, but the placenta has been poorly studied so far. (2) Methods: To decipher the origin of this metabolic reprogramming, we conducted a targeted metabolomics study replicated in two cohorts of placenta and one cohort of cord blood by measuring 188 metabolites by mass spectrometry. (3) Results: OPLS-DA multivariate analyses enabled clear discriminations between IUGR and controls, with good predictive capabilities and low overfitting in the two placental cohorts and in cord blood. A signature of 25 discriminating metabolites shared by both placental cohorts was identified. This signature points to sharp impairment of lipid and mitochondrial metabolism with an increased reliance on the creatine-phosphocreatine system by IUGR placentas. Increased placental insulin resistance and significant alteration of fatty acids oxidation, together with relatively higher phospholipase activity in IUGR placentas, were also highlighted. (4) Conclusions: Our results show a deep lipid and energetic remodeling in IUGR placentas that may have a lasting effect on the fetal metabolism.

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Study of mitochondrial function in placental insufficiency

Cited by 12 publications

References 25 publications

Mitochondrial Bioenergetics in Placenta of Crossbred Cattle- Deciphering the Association of Mitochondrial Alterations with Retained Placenta

Mitochondrial Bioenergetics in Placenta of Crossbred Cattle- Deciphering the Association of Mitochondrial Alterations with Retained Placenta

Mitochondrial implications in human pregnancies with intrauterine growth restriction and associated cardiac remodelling

A Metabolomic Profiling of Intra-Uterine Growth Restriction in Placenta and Cord Blood Points to an Impairment of Lipid and Energetic Metabolism

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