Maternal aging affects oocyte resilience to carbonyl cyanide-m-chlorophenylhydrazone -induced mitochondrial dysfunction in cows

Kansaku, Kazuki; Takeo, Shun; Itami, Nobuhiko; Kin, Airi; Shirasuna, Koumei; Kuwayama, Takehito; Iwata, Hisataka

doi:10.1371/journal.pone.0188099

Cited by 27 publications

(21 citation statements)

References 35 publications

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“…CCCP treatment has been used to enhance mitochondrial quality control in cells [ 20 ]. We showed that CCCP treatment of bovine and porcine COCs did not reduce developmental ability but enhanced mitochondrial biogenesis and degradation in oocytes [ 13 , 21 ]. From these facts, it is conceivable that short duration of CCCP treatment may reversibly affect mitochondrial conditions in oocytes and cells, and enhance mitochondrial kinetics in both cells.…”

Section: Discussionmentioning

confidence: 99%

Mitochondrial dysfunction in cumulus-oocyte complexes increases cell-free mitochondrial DNA

Kansaku

Munakata

Itami

et al. 2018

Journal of Reproduction and Development

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This study examined the concentration of cell-free mitochondrial DNA (cf-mtDNA) in porcine follicular fluid (FF) and explored whether the cfDNA level in the culture medium could reflect mitochondrial dysfunction in cumulus cell-oocyte complexes (COCs). cfDNA concentration was higher in the fluid of small-sized follicles, compared to that in larger follicles. The length of cfDNA ranged from short (152 bp) to long (1,914 bp) mtDNA in FF, detected by polymerase chain reaction (PCR). cfDNA concentration in FF significantly correlated with the mtDNA copy number in FF but not with the number of one-copy gene (nuclear DNA) in FF. When the COCs were treated with the mitochondrial uncoupler, namely carbonyl cyanide m-chlorophenyl hydrazone (CCCP), for 2 h and incubated for 42 h, subsequent real-time PCR detected significantly higher amount of cf-mtDNA, compared to nuclear cfDNA, in the spent culture medium. The mtDNA number and viability of cumulus cells and oocytes remained unchanged. When the oocytes were denuded from the cumulus cells following CCCP treatment, PCR detected very low levels of cfDNA in the spent culture medium of the denuded oocytes. In contrast, CCCP treatment of granulosa cells significantly increased the amount of cf-mtDNA in the spent culture medium, without any effect on other markers, including survival rate, apoptosis of cumulus cells, and lactate dehydrogenase levels. Thus, cf-mtDNA was present in FF in a wide range of length, and mitochondrial dysfunction in COCs increased the active secretion of cf-mtDNA in the cultural milieu.

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Section: Discussionmentioning

confidence: 99%

Mitochondrial dysfunction in cumulus-oocyte complexes increases cell-free mitochondrial DNA

Kansaku

Munakata

Itami

et al. 2018

Journal of Reproduction and Development

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“…Treatment of porcine oocytes with resveratrol increased mitochondrial biogenesis and degradation in the oocytes, through SIRT1 activation and improved their developmental ability [ 10 ]. Moreover, CCCP-induced mitochondrial dysfunction has been found to differentially influence oocyte developmental ability and mitochondrial synthesis between young and aged cows; the differential mitochondrial response may be attributed to the differential activation of SIRT1 between the two age groups following CCCP treatment [ 11 ]. Based on these studies, it may be suggested that the up-regulation of SIRT1 expression induced by resveratrol may attenuate mitochondrial dysfunction in oocytes and embryos.…”

Section: Introductionmentioning

confidence: 99%

Resveratrol enhances the clearance of mitochondrial damage by vitrification and improves the development of vitrified-warmed bovine embryos

Hara¹,

Kin²,

Aoki³

et al. 2018

PLoS ONE

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The present study investigated the vitrification-induced deterioration of mitochondrial functions that may reduce the developmental ability of post-warming bovine embryos. In addition, the effect of supplementation of the culture medium with resveratrol on the mitochondrial functions and post-warming embryonic development was examined. Two days after in vitro fertilization, embryos with 8–12 cells (referred to hereafter as 8-cell embryos) were vitrified and warmed, followed by in vitro incubation for 5 days in a culture medium containing either the vehicle or 0.5 μM resveratrol. Vitrification reduced embryonic development until the blastocyst stage, reduced the ATP content of embryos, and impaired the mitochondrial genome integrity, as determined by real-time polymerase chain reaction. Although the total cell number and mitochondrial DNA copy number (Mt-number) of blastocysts were low in the vitrified embryos, the Mt-number per blastomere was similar among the blastocysts derived from fresh (non-vitrified) and vitrified-warmed embryos. Supplementation of the culture medium with resveratrol enhanced the post-warming embryonic development and reduced the Mt-number and reactive oxygen species level in blastocysts and blastomeres without affecting the ATP content. An increase in the content of cell-free mitochondrial DNA in the spent culture medium was observed following cultivation of embryos with resveratrol. These results suggested that vitrification induces mitochondrial damages and that resveratrol may enhance the development of post-warming embryos and activates the degeneration of damaged mitochondria, as indicated by the increase in the cell-free mitochondrial DNA content in the spent culture medium and the decrease in the Mt-number of blastocysts and blastomeres.

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“…Ageing has a well described effect on mitochondrial quantity and quality (Pantos et al 1999, Iwata et al 2011, Bartmann et al 2004. The oocyte quality decreases with maternal age and the ageassociated mitochondrial deterioration is closely related to this decline in oocyte quality (Pantos et al 1999, Tilly and Sinclair 2013, Kansaku et al 2017b. Several studies described a decrease in the mitochondrial DNA copy number, decline in the ATP content and increased levels of reactive oxygen species (ROS) in oocytes in different Vol.…”

Section: Energy Metabolism Of Granulosa Cells and Oocytesmentioning

confidence: 99%

“…Several studies described a decrease in the mitochondrial DNA copy number, decline in the ATP content and increased levels of reactive oxygen species (ROS) in oocytes in different Vol. 69 animal species (Simsek-Duran et al 2013, Rambags et al 2014, Kansaku et al 2017b. Kansaku et al (2017b) described a lower level of mitochondrial biogenesis and an inadequate activation of mitochondrial biogenesis in response to uncoupler-induced mitochondrial dysfunction in oocytes of aged cows.…”

Section: Energy Metabolism Of Granulosa Cells and Oocytesmentioning

confidence: 99%

Metabolic Cooperation in the Ovarian Follicle

et al. 2020

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Granulosa cells (GCs) are somatic cells essential for establishing and maintaining bi-directional communication with the oocytes. This connection has a profound importance for the delivery of energy substrates, structural components and ions to the maturing oocyte through gap junctions. Cumulus cells, group of closely associated GCs, surround the oocyte and can diminished the effect of harmful environmental insults. Both GCs and oocytes prefer different energy substrates in their cellular metabolism: GCs are more glycolytic, whereas oocytes rely more on oxidative phosphorylation pathway. The interconnection of these cells is emphasized by the fact that GCs supply oocytes with intermediates produced in glycolysis. The number of GCs surrounding the oocyte and their age affect the energy status of oocytes. This review summarises available studies collaboration of cellular types in the ovarian follicle from the point of view of energy metabolism, signaling and protection of toxic insults. A deeper knowledge of the underlying mechanisms is crucial for better methods to prevent and treat infertility and to improve the technology of in vitro fertilization.

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Maternal aging affects oocyte resilience to carbonyl cyanide-m-chlorophenylhydrazone -induced mitochondrial dysfunction in cows

Cited by 27 publications

References 35 publications

Mitochondrial dysfunction in cumulus-oocyte complexes increases cell-free mitochondrial DNA

Mitochondrial dysfunction in cumulus-oocyte complexes increases cell-free mitochondrial DNA

Resveratrol enhances the clearance of mitochondrial damage by vitrification and improves the development of vitrified-warmed bovine embryos

Metabolic Cooperation in the Ovarian Follicle

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