Sperm-triggered [Ca2+] oscillations and Ca2+homeostasis in the mouse egg have an absolute requirement for mitochondrial ATP production

Dumollard, Rémi; Marangos, Petros; FitzHarris, Greg; Swann, Karl; Duchen, Michael R.; Carroll, John

doi:10.1242/dev.01181

Cited by 217 publications

(186 citation statements)

References 50 publications

(60 reference statements)

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“…mtDNA mitochondrial DNA, PBCs peripheral blood cells, CCs cumulus cells oocytes were surrounded by CCs [17]. At fertilization, mitochondrion-derived ATP is essential for sperm-triggered oscillations [18]. Oocyte aging has been proposed to occur in association with mitochondrial dysfunction resulting from the accumulation of point mutations and decreased mtDNA content [5,19].…”

Section: Discussionmentioning

confidence: 99%

Mitochondrial DNA copy number in cumulus cells is a strong predictor of obtaining good-quality embryos after IVF

Ogino

Taniguchi

Sakata

et al. 2016

J Assist Reprod Genet

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Purpose The aim of this study was to establish a simple tool to predict good-quality embryos in in vitro fertilization (IVF) by using cumulus cells (CCs) or peripheral blood cells (PBCs). Methods Mitochondrial DNA was extracted from CCs and PBCs in patients undergoing IVF. Using real-time polymerase chain reaction, mtDNA copy number in a single cell was calculated. Embryo quality was assessed when it was transferred or frozen. Results CCs were obtained from 60 oocyte cumulus-cell complexes (OCCCs) in 30 women, and PBCs were collected from 18 women. For the 30 women in the study, the median age was 37 years old (range, 24-43), and the mean body mass index was 21.4 (standard error, 2.0). mtDNA content of CCs and PBCs was highly correlated (Pearson's r = 0.900, p < 0.0001). The median mtDNA content of CCs for goodand poor-quality embryos was 140 and 57, respectively (p < 0.0001). The median mtDNA content of PBCs for goodand poor-quality embryos was 36 and 13, respectively (p = 0.604). The logistic regression model indicated that mtDNA content in CCs was the only parameter that predicted good-quality embryos (p = 0.020). The receiver operating characteristic curve for obtaining good-quality embryos by mtDNA copy number in CCs had an area under the curve of 0.823, and using a threshold of 86, positive and negative predictive values were 84.4 and 82.1 %, respectively. Conclusions The determination of mtDNA content in CCs can be used to predict good-quality embryos.

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Section: Discussionmentioning

confidence: 99%

Mitochondrial DNA copy number in cumulus cells is a strong predictor of obtaining good-quality embryos after IVF

Ogino

Taniguchi

Sakata

et al. 2016

J Assist Reprod Genet

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“…The average increase in fluorescence per unit area of the mitochondria was determined and plotted for both conditions. Next, embryos were isolated and treated with Tyrode's acid solution to remove the zona pellucida (Dumollard et al 2004) and then loaded with TMRM. Individual embryos were then allowed to attach in an eight-well chamber dish by plating them in minimal amount of M2 medium lacking BSA.…”

Section: Effect Of Serotonin On Mitochondrial Potentialmentioning

confidence: 99%

Serotonin in pre-implantation mouse embryos is localized to the mitochondria and can modulate mitochondrial potential

Basu¹,

Desai²,

Balaji³

et al. 2008

Reproduction

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Serotonin is reported to be present in early embryos of many species and plays an important role in early patterning. Since it is a fluorophore, it can be directly visualized using fluorescence microscopy. Here, we use three-photon microscopy to image serotonin in live pre-implantation mouse embryos. We find that it is present as puncta averaging 1.3 square microns and in concentrations as high as 442 mM. The observed serotonin puncta were found to co-localize with mitochondria. Live embryos pre-incubated with serotonin showed a higher mitochondrial potential, indicating that it can modulate mitochondrial potential. Pre-implantation mouse embryos were also examined at various developmental stages for the presence of transcripts of the peripheral and neuronal forms of tryptophan hydroxylase (Tph1 and Tph2 respectively) and the classical serotonin transporter (Slc6a4). Transcripts of Tph2 were seen in oocytes and in two-cell stages, whereas transcripts of Tph1 were not detected at any stage. Transcripts of the transporter, Slc6a4, were present in all pre-implantation stages investigated. These results suggest that serotonin in embryos can arise from a combination of synthesis and uptake from the surrounding milieu.

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“…Although the "immature" mitochondria in mammalian fertilized eggs differ from the "mature" mitochondria in somatic cells, the "immature" mitochondria are also involved in the early phase of oxidative stress-induced apoptosis [23]. In mouse oocytes and embryos, constant levels of ATP are maintained by active mitochondrial oxidative phosphorylation [9,38].…”

Section: Introductionmentioning

confidence: 99%

Nitric oxide modulates mitochondrial activity and apoptosis through protein S-nitrosylation for preimplantation embryo development

Lee¹,

Lee²,

Huang³

et al. 2013

J Assist Reprod Genet

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Purpose Previous studies reported that patients with endometriosis had excess nitric oxide (NO) in the reproductive tract and poor embryo development in IVF cycles. This study aims to elucidate the effects of NO on early embryo development. Methods Zygotes from superovulated B6CBF1 mice were cultured to blastocysts in a variety of media. Sodium nitroprusside (SNP) and N G -nitro-L-arginine (LNA) were added to the culture medium as a NO donor and a NO synthase inhibitor, respectively. The localization and fluorescence intensity of S-nitrosylated (SNO) proteins within 2-cell stage embryos were analyzed with confocal microscopy. Apoptosis and ATP production in the blastocysts were measured. Result(s) Subsequent to NO exposure, the SNO proteins mainly colocalized with the mitochondria and endoplasmic reticulum and the intensity of SNO proteins increased. The addition of a quanylate cyclase inhibitor and a cyclic GMP mimic agent induced nonsignificant changes in SNO proteins, whereas addition of a superoxide scavenger or a reduced form of glutathione rescued the embryos from the effects of NO. However, superoxide scavenger supplementation resulted in decreased blastocyst ATP production. Conclusion(s) Elevated NO exerts deleterious effects on embryo development, possibly through protein S-nitrosylation in the mitochondria and endoplasmic reticulum. Including glutathione as a component in the culture medium might counteract this effect.

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Sperm-triggered [Ca2+] oscillations and Ca2+homeostasis in the mouse egg have an absolute requirement for mitochondrial ATP production

Cited by 217 publications

References 50 publications

Mitochondrial DNA copy number in cumulus cells is a strong predictor of obtaining good-quality embryos after IVF

Mitochondrial DNA copy number in cumulus cells is a strong predictor of obtaining good-quality embryos after IVF

Serotonin in pre-implantation mouse embryos is localized to the mitochondria and can modulate mitochondrial potential

Nitric oxide modulates mitochondrial activity and apoptosis through protein S-nitrosylation for preimplantation embryo development

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