Higher Mitochondrial DNA Content in Human IUGR Placenta

Lattuada, D.; Colleoni, F.; Martinelli, Anna; Garretto, A.; Magni, R.; Radaelli, Tatjana; Cetin, Irene

doi:10.1016/j.placenta.2008.09.012

Cited by 91 publications

(59 citation statements)

References 22 publications

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“…We found that mtDNA content was higher in placentas of the IUGR group than in control placentas. This is in agreement with our previously reported results (28) and complies with NRF1 gene expression levels, which were increased, though not significantly, in IUGR placentas. On the other hand, mtDNA placental content of the PE group was not significantly different from control placentas.…”

Section: Discussionsupporting

confidence: 94%

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Placental mitochondrial content and function in intrauterine growth restriction and preeclampsia

Mandò

Palma

Stampalija

et al. 2014

American Journal of Physiology-Endocrinology and Metabolism

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164

132

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Intrauterine growth restriction (IUGR) and pregnancy hypertensive disorders such as preeclampsia (PE) associated with IUGR share a common placental phenotype called “placental insufficiency”, originating in early gestation when high availability of energy is required. Here, we assess mitochondrial content and the expression and activity of respiratory chain complexes (RCC) in placental cells of these pathologies. We measured mitochondrial (mt)DNA and nuclear respiratory factor 1 ( NRF1) expression in placental tissue and cytotrophoblast cells, gene and protein expressions of RCC (real-time PCR and Western blotting) and their oxygen consumption, using the innovative technique of high-resolution respirometry. We analyzed eight IUGR, six PE, and eight uncomplicated human pregnancies delivered by elective cesarean section. We found lower mRNA levels of complex II, III, and IV in IUGR cytotrophoblast cells but no differences at the protein level, suggesting a posttranscriptional compensatory regulation. mtDNA was increased in IUGR placentas. Both mtDNA and NRF1 expression were instead significantly lower in their isolated cytotrophoblast cells. Finally, cytotrophoblast RCC activity was significantly increased in placentas of IUGR fetuses. No significant differences were found in PE placentas. This study provides genuine new data into the complex physiology of placental oxygenation in IUGR fetuses. The higher mitochondrial content in IUGR placental tissue is reversed in cytotrophoblast cells, which instead present higher mitochondrial functionality. This suggests different mitochondrial content and activity depending on the placental cell lineage. Increased placental oxygen consumption might represent a limiting step in fetal growth restriction, preventing adequate oxygen delivery to the fetus.

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Section: Discussionsupporting

confidence: 94%

“…We have previously reported higher mitochondrial DNA (mtDNA) levels in placenta and maternal blood of human IUGR (13,28). mtDNA levels are largely recognized as a measure of the mitochondrial content (25,36,37,58) and are regulated by different mitochondrial biogenesis activators in several tissues (41,6).…”

mentioning

confidence: 99%

Placental mitochondrial content and function in intrauterine growth restriction and preeclampsia

Mandò

Palma

Stampalija

et al. 2014

American Journal of Physiology-Endocrinology and Metabolism

Self Cite

164

132

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“…Therefore, lower placental glutamine concentrations possibly deriving from SNAT2 decrease may lead to mitochondrial oxidative stress and cell distress, resulting in alterations in cell metabolism and the biosynthesis of molecules (such as progesterone) that are fundamental for pregnancy maintenance (24). Indeed, these are typical characteristics leading to the IUGR condition, and mitochondrial alterations have been reported in human IUGR placentas (25).…”

Section: Discussionmentioning

confidence: 99%

SNAT2 expression and regulation in human growth-restricted placentas

et al. 2013

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Background: Amino acid placental delivery is reduced in human intrauterine growth-restricted (IUGR) fetuses, and the activity of placental amino transporters has been consistently shown to be decreased in in vitro studies. We hypothesized lower placental expression and localization of sodium-coupled neutral amino acid transporter 2 (SNAT2 (also known as SLC38A2)), altered levels of intron-1 methylation, and altered distribution of single-nucleotide polymorphisms in human IUGR vs. normal pregnancies. Methods: We studied 88 IUGR and 84 control placentas from singleton pregnancies at elective caesarean section. SNAT2 expression was investigated by real-time PCR and immunohistochemistry. Intron-1 methylation levels were analyzed by pyrosequencing, and single-nucleotide polymorphism distribution was analyzed by allelic discrimination. results: mRNA levels were significantly decreased in IUGR placentas with reduced umbilical blood flows. Syncytiotrophoblast immunostaining was lower in IUGR placentas than in control placentas. Methylation levels were steadily low in both IUGR and control placentas. SNP genotype and allele frequencies did not differ between the two groups. conclusion: This is the first study investigating SNAT2 expression and regulation mechanisms in human IUGR placentas. We confirm previous results obtained in rats and cell cultures that support the fundamental role of SNAT2 in fetal growth and well-being, as well as a possible role of oxygen levels in regulating SNAT2 expression, indicating the relevance of hypoxia in IUGR.

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“…As mentioned above, cffDNA can trigger inflammation and adverse pregnancy outcomes in mice via TLR9 (Scharfe-Nugent et al 2012). Similarly, mitochondrial DNA (mtDNA) is released by trophoblasts upon death and its levels in maternal circulation are increased in PE (and IUGR) (Lattuada et al 2008, Goulopoulou et al 2012, Qiu et al 2012; the immunostimulatory and pro-inflammatory role of mitochondrial DNA in PE has been reviewed elsewhere (McCarthy & Kenny 2016). Activation of TLR9 by fetal or mitochondrial cell-free DNA, or other mediators (including HMGB1), has been suggested to lead to vascular dysfunction and hypertension (Goulopoulou et al 2012).…”

Section: Cffdnamentioning

confidence: 99%

Sterile inflammation and pregnancy complications: a review

Nadeau-Vallée¹,

Obari²,

Palacios³

et al. 2016

Reproduction

218

161

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Inflammation is essential for successful embryo implantation, pregnancy maintenance and delivery. In the last decade, important advances have been made in regard to endogenous, and therefore non-infectious, initiators of inflammation, which can act through the same receptors as pathogens. These molecules are referred to as damage-associated molecular patterns (DAMPs), and their involvement in reproduction has only recently been unraveled. Even though inflammation is necessary for successful reproduction, untimely activation of inflammatory processes can have devastating effect on pregnancy outcomes. Many DAMPs, such as uric acid, high-mobility group box 1 (HMGB1), interleukin (IL)-1 and cell-free fetal DNA, have been associated with pregnancy complications, such as miscarriages, preeclampsia and preterm birth in preclinical models and in humans. However, the specific contribution of alarmins to these conditions is still under debate, as currently there is lack of information on their mechanism of action. In this review, we discuss the role of sterile inflammation in reproduction, including early implantation and pregnancy complications. Particularly, we focus on major alarmins vastly implicated in numerous sterile inflammatory processes, such as uric acid, HMGB1, IL-1α and cell-free DNA (especially that of fetal origin) while giving an overview of the potential role of other candidate alarmins.Reproduction (2016) 152 R277-R292

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Higher Mitochondrial DNA Content in Human IUGR Placenta

Cited by 91 publications

References 22 publications

Placental mitochondrial content and function in intrauterine growth restriction and preeclampsia

Placental mitochondrial content and function in intrauterine growth restriction and preeclampsia

SNAT2 expression and regulation in human growth-restricted placentas

Sterile inflammation and pregnancy complications: a review

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