Reduced amount of cytochrome <i>c</i> oxidase subunit I messenger RNA in placentas from pregnancies complicated by preeclampsia

Lin, He; Wang, Zehua; Sun, Yu

doi:10.1111/j.0001-6349.2004.00345.x

Cited by 17 publications

(9 citation statements)

References 21 publications

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“…In addition, electron microscopic studies also revealed less abundant mitochondria, and consistently, the placental mitochondrial DNA copy number, which is a measure of mitochondrial content [ 47 ], was strongly decreased in the placenta of T rats. Similar mitochondrial structural damage and reduced numbers are observed in the placenta and cytotrophoblasts of PE women and in other placental insufficiency conditions [ 7 , 10 , 11 , 47 , 48 ]. Although the sex-dependent impacts of T on placental mitochondrial structure and function were not examined in this study, it will be an interesting aspect to examine in the future.…”

Section: Discussionsupporting

confidence: 59%

Testosterone Decreases Placental Mitochondrial Content and Cellular Bioenergetics

Mishra

Selvanesan

Kumar

2020

Biology

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Placental mitochondrial dysfunction plays a central role in the pathogenesis of preeclampsia. Since preeclampsia is a hyperandrogenic state, we hypothesized that elevated maternal testosterone levels induce damage to placental mitochondria and decrease bioenergetic profiles. To test this hypothesis, pregnant Sprague–Dawley rats were injected with vehicle or testosterone propionate (0.5 mg/kg/day) from gestation day (GD) 15 to 19. On GD20, the placentas were isolated to assess mitochondrial structure, copy number, ATP/ADP ratio, and biogenesis (Pgc-1α and Nrf1). In addition, in vitro cultures of human trophoblasts (HTR-8/SVneo) were treated with dihydrotestosterone (0.3, 1.0, and 3.0 nM), and bioenergetic profiles using seahorse analyzer were assessed. Testosterone exposure in pregnant rats led to a 2-fold increase in plasma testosterone levels with an associated decrease in placental and fetal weights compared with controls. Elevated maternal testosterone levels induced structural damage to the placental mitochondria and decreased mitochondrial copy number. The ATP/ADP ratio was reduced with a parallel decrease in the mRNA and protein expression of Pgc-1α and Nrf1 in the placenta of testosterone-treated rats compared with controls. In cultured trophoblasts, dihydrotestosterone decreased the mitochondrial copy number and reduced PGC-1α, NRF1 mRNA, and protein levels without altering the expression of mitochondrial fission/fusion genes. Dihydrotestosterone exposure induced significant mitochondrial energy deficits with a dose-dependent decrease in basal respiration, ATP-linked respiration, maximal respiration, and spare respiratory capacity. In summary, our study suggests that the placental mitochondrial dysfunction induced by elevated maternal testosterone might be a potential mechanism linking preeclampsia to feto-placental growth restriction.

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Section: Discussionsupporting

confidence: 59%

Testosterone Decreases Placental Mitochondrial Content and Cellular Bioenergetics

Mishra

Selvanesan

Kumar

2020

Biology

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“…However, there are two explanations for that. First, downregulation of the expression and activity of placental cytochrome c oxidase, a mitochondrial respiratory chain enzyme, in women with PE may lead to impaired mitochondrial energy production (Zehua et al 1999;He et al 2004). Second, hypoxia (due to impaired placentation) may downregulate the expression and activity of organic cation/carnitine transporter (OCTN2) in human trophoblasts (Rytting and Audus 2007).…”

Section: Lipid Metabolism and Its Related Metabolitesmentioning

confidence: 99%

Application of metabolomics to preeclampsia diagnosis

2018

Systems Biology in Reproductive Medicine

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PE: preeclampsia; sFlt-1: soluble FMS-like tyrosine kinase-1; PlGF: placental growth factor; GC-MS: gas chromatography-mass spectrometry; LC-MS: liquid chromatography-mass spectrometry; NMR: nuclear magnetic resonance spectroscopy; HMDB: human metabolome database; RCT: randomized control trial; e-PE: early-onset PE; l-PE: late-onset PE; PLS-DA: partial least-squares-discriminant analysis; CRL: crown-rump length; UtPI: uterine artery Doppler pulsatility index; BMI: body mass index; MAP: mean arterial pressure; OS: oxidative stress; PAPPA: plasma protein A; FTIR: Fourier transform infrared; BCAA: branched chain amino acids; Arg: arginine; NO: nitric oxide.

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“…Studies in skeletal muscle cells (L6 myotubes) have described direct interactions between PGC-1α/ERRα, increased creatine transporter mRNA expression and cellular creatine up-take [32]. As there have been mixed reports of increases and decreases to placental mitochondrial content and PGC-1α expression with PE [33,34], further exploration of this mechanistic pathway is required before conclusions about AMPK's role in driving changes to creatine transport and cellular up-take in PE placentae can be drawn. In vitro techniques should be employed for these analyses to control for changes in placental metabolism associated with tissue collection and processing times.…”

Section: Discussionmentioning

confidence: 99%

The Effects of Early-Onset Pre-Eclampsia on Placental Creatine Metabolism in the Third Trimester

Ellery

Murthi

Gatta

et al. 2020

IJMS

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Creatine is a metabolite important for cellular energy homeostasis as it provides spatio-temporal adenosine triphosphate (ATP) buffering for cells with fluctuating energy demands. Here, we examined whether placental creatine metabolism was altered in cases of early-onset pre-eclampsia (PE), a condition known to cause placental metabolic dysfunction. We studied third trimester human placentae collected between 27–40 weeks’ gestation from women with early-onset PE (n = 20) and gestation-matched normotensive control pregnancies (n = 20). Placental total creatine and creatine precursor guanidinoacetate (GAA) content were measured. mRNA expression of the creatine synthesizing enzymes arginine:glycine aminotransferase (GATM) and guanidinoacetate methyltransferase (GAMT), the creatine transporter (SLC6A8), and the creatine kinases (mitochondrial CKMT1A & cytosolic BBCK) was assessed. Placental protein levels of arginine:glycine aminotransferase (AGAT), GAMT, CKMT1A and BBCK were also determined. Key findings; total creatine content of PE placentae was 38% higher than controls (p < 0.01). mRNA expression of GATM (p < 0.001), GAMT (p < 0.001), SLC6A8 (p = 0.021) and BBCK (p < 0.001) was also elevated in PE placentae. No differences in GAA content, nor protein levels of AGAT, GAMT, BBCK or CKMT1A were observed between cohorts. Advancing gestation and birth weight were associated with a down-regulation in placental GATM mRNA expression, and a reduction in GAA content, in control placentae. These relationships were absent in PE cases. Our results suggest PE placentae may have an ongoing reliance on the creatine kinase circuit for maintenance of cellular energetics with increased total creatine content and transcriptional changes to creatine synthesizing enzymes and the creatine transporter. Understanding the functional consequences of these changes warrants further investigation.

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Reduced amount of cytochrome c oxidase subunit I messenger RNA in placentas from pregnancies complicated by preeclampsia

Abstract: Our study demonstrates a reduced amount of cytochrome c oxidase subunit I mRNA in preeclamptic placentas compared to control placentas. We hypothesize that a reduced expression may play a role in the pathophysiology of preeclampsia.

Cited by 17 publications

References 21 publications

Testosterone Decreases Placental Mitochondrial Content and Cellular Bioenergetics

Testosterone Decreases Placental Mitochondrial Content and Cellular Bioenergetics

Application of metabolomics to preeclampsia diagnosis

The Effects of Early-Onset Pre-Eclampsia on Placental Creatine Metabolism in the Third Trimester

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