The activity and copy number of mitochondrial DNA in ovine oocytes throughout oogenesis in vivo and during oocyte maturation in vitro

Cotterill, Matthew; Harris, Sarah E.; Fernandez, Esther Collado; Lu, Jianping; Huntriss, John; Campbell, Bruce; Picton, Helen M.

doi:10.1093/molehr/gat013

Cited by 94 publications

(72 citation statements)

References 52 publications

(102 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Although active mitochondrial biogenesis has been reported in oocytes [15], [27], little is known about mitochondrial homeostasis in these cells.…”

Section: Discussionmentioning

confidence: 99%

“…Mitochondrial number can be predicted by quantifying the mitochondrial DNA copy number (Mt number) using real time-PCR, based on reports that mitochondria in oocytes typically contain one copy of the mitochondrial genome [4]. The Mt-number in bovine oocytes increases during the growth of oocytes from early antral follicles to antral follicles in vivo and in vitro [5], [6], and the number remains the same or increases further during oocyte maturation [5], [7], [8]. However, little is known about how culture conditions affect Mt number in oocytes.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Relationship between mitochondrial DNA Copy Number and SIRT1 Expression in Porcine Oocytes

et al. 2014

View full text Add to dashboard Cite

The present study assessed the effect of resveratrol on the expression of SIRT1 and mitochondrial quality and quantity in porcine oocytes. Supplementing the maturation medium with 20 µM resveratrol increased the expression of SIRT1, and enhanced mitochondrial functions, as observed from the increased ATP content and mitochondrial membrane potential. Addition of resveratrol also improved the ability of oocytes to develop into the blastocyst stage following activation. The effects of resveratrol on mitochondrial number were examined by comparing the mitochondrial DNA copy number (Mt number) between group of oocytes collected from the same donor gilt ovaries. Supplementing the maturation medium with only resveratrol did not affect the Mt number in the oocytes. However, supplementing the maturation medium with 10 µM MG132, a proteasome inhibitor, significantly increased the amount of ubiquitinated proteins and Mt number by 12 and 14%, respectively. In addition, when resveratrol was added to the medium containing MG132, the Mt number increased significantly by 39%, this effect was diminished by the addition of the SIRT1 inhibitor EX527. Furthermore, supplementing the medium with MG132 and EX527 did not affect Mt number. The mean SIRT1 expression in 20 oocytes was significantly and positively correlated with the Mt number in oocytes collected from the same donor. This study suggests that the expression of SIRT1 is associated with the Mt number in oocytes. In addition, activation of SIRT1 by resveratrol enhances the biosynthesis and degradation of mitochondria in oocytes, thereby replenishing and improving mitochondrial function and the developmental ability of oocytes.

show abstract

“…Although active mitochondrial biogenesis has been reported in oocytes [15], [27], little is known about mitochondrial homeostasis in these cells.…”

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Relationship between mitochondrial DNA Copy Number and SIRT1 Expression in Porcine Oocytes

et al. 2014

View full text Add to dashboard Cite

show abstract

“…Mitochondrial quality and quantity are believed to be important for oocyte maturation, fertilization and subsequent development (Reynier et al 2001, Thouas et al 2004, Santos et al 2006. It has been reported that the mitochondrial number increases during oocyte development (Cotterill et al 2013). Early embryonic development may be supported by whole, already existing mitochondria without de novo synthesis (Wai et al 2010), although a few studies suggest that de novo mitochondrial synthesis occurs during early embryonic development (Chiaratti et al 2010).…”

Section: Introductionmentioning

confidence: 99%

“…Early embryonic development may be supported by whole, already existing mitochondria without de novo synthesis (Wai et al 2010), although a few studies suggest that de novo mitochondrial synthesis occurs during early embryonic development (Chiaratti et al 2010). Furthermore, it has been suggested that once mitochondrial number reaches a certain threshold during oocyte maturation, this number is maintained (Mahrous et al 2012, Cotterill et al 2013), but Mao et al (2012) reported that mitochondrial synthesis is induced by supplementation of maturation medium with follicular fluid (FF) and neuregulin 1. Despite the presence of both de novo synthesis and degradation pathways in somatic cells, mitochondrial turnover during oocyte maturation has not been investigated.…”

Section: Introductionmentioning

confidence: 99%

Mitochondrial biogenesis and degradation are induced by CCCP treatment of porcine oocytes

et al. 2015

View full text Add to dashboard Cite

In this study, we investigated the mitochondrial quality control system in porcine oocytes during meiotic maturation. Cumulus cell oocyte complexes (COCs) collected from gilt ovaries were treated with 10 mM carbonyl cyanide-m-chlorophenylhydrazone (CCCP; a mitochondrial uncoupler) for 2 h. The CCCP treatment was found to significantly reduce ATP content, increase the amount of phosphorylated AMP-activated protein kinase and elevate reactive oxygen species levels in oocytes. When the CCCP-treated COCs were cultured further for 44 h in maturation medium, the ATP levels were restored and the parthenogenetic developmental rate of oocytes to the blastocyst stage was comparable with that of untreated COCs. To examine the effects of CCCP treatment of oocytes on the kinetics of mitochondrial DNA copy number (Mt number), COCs treated with 0 or 10 mM CCCP were cultured for 44 h, after which the Mt number was determined by RT-PCR. CCCP treatment was found to increase the Mt number in the modified maturation medium in which mitochondrial degradation was inhibited by MG132, whereas CCCP treatment did not affect the Mt number in the maturation medium lacking MG132. The relative gene expression of TFAM was furthermore shown to be significantly higher in CCCP-treated oocytes than in untreated oocytes. Taken together, the finding presented here suggest that when the mitochondria are injured, mitochondrial biogenesis and degradation are induced, and that these processes may contribute to the recuperation of oocytes.Reproduction (2015) 150 97-104

show abstract

“…In both cases, the defect would have originated from the population of mtDNA that segregated to the primordial germ cells during early fetal development (Cree et al 2008;Rebolledo-Jaramillo et al 2014). The primordial germ cells are the first identifiable germ cells and their constituent population of mtDNA copies increases exponentially during oogenesis Cotterill et al 2013). Consequently, mtDNA variants have the propensity to populate oocytes at differing levels, which can give rise to mitochondrial disease in the offspring (Shoubridge and Wai 2007).…”

mentioning

confidence: 99%

Segregation of Naturally Occurring Mitochondrial DNA Variants in a Mini-Pig Model

et al. 2016

View full text Add to dashboard Cite

The maternally inherited mitochondrial genome (mtDNA) is present in multimeric form within cells and harbors sequence variants (heteroplasmy). While a single mtDNA variant at high load can cause disease, naturally occurring variants likely persist at low levels across generations of healthy populations. To determine how naturally occurring variants are segregated and transmitted, we generated a mini-pig model, which originates from the same maternal ancestor. Following next-generation sequencing, we identified a series of low-level mtDNA variants in blood samples from the female founder and her daughters. Four variants, ranging from 3% to 20%, were selected for validation by high-resolution melting analysis in 12 tissues from 31 animals across three generations. All four variants were maintained in the offspring, but variant load fluctuated significantly across the generations in several tissues, with sexspecific differences in heart and liver. Moreover, variant load was persistently reduced in high-respiratory organs (heart, brain, diaphragm, and muscle), which correlated significantly with higher mtDNA copy number. However, oocytes showed increased heterogeneity in variant load, which correlated with increased mtDNA copy number during in vitro maturation. Altogether, these outcomes show that naturally occurring mtDNA variants segregate and are maintained in a tissue-specific manner across generations. This segregation likely involves the maintenance of selective mtDNA variants during organogenesis, which can be differentially regulated in oocytes and preimplantation embryos during maturation.KEYWORDS mitochondrial DNA; segregation; variants; generations; embryo W HILE the nuclear genome is inherited from both parents, the mitochondrial genome (mtDNA) is only inherited from the population present in the oocyte at fertilization (Chinnery et al. 2000). The porcine mitochondrial genome is 16.7 kb in size and encodes 13 of the subunits of the electron transport chain, which drives ATP synthesis through the biochemical process of oxidative phosphorylation (OXPHOS) (Ursing and Arnason 1998). It also encodes 22 transfer RNAs (tRNAs), which are interspersed between the encoding genes, and 2 ribosomal RNA (rRNA) complexes. mtDNA is located in the mitochondrial matrix and is tethered to proteins, which collectively form the mitochondrial nucleoid (Kucej and Butow 2007). mtDNA is present in multiple copies within cells and these genomes can be polymorphic. Consequently, cells can inherently harbor variant and wild-type (WT) sequences, i.e., heteroplasmic populations, of mtDNA at different frequencies (Wallace and Chalkia 2013).Most mtDNA variants are nonpathogenic (Ramos et al. 2013) but specific nucleotide mutations and large-scale deletions can lead to molecular defects, resulting in a wide range of clinical conditions, known as mitochondrial diseases (McFarland et al. 2007). Within the spectrum of mitochondrial diseases, the onset of symptoms can vary according to Copyright © 2016 Apart from the occurrence o...

show abstract

The activity and copy number of mitochondrial DNA in ovine oocytes throughout oogenesis in vivo and during oocyte maturation in vitro

Cited by 94 publications

References 52 publications

Relationship between mitochondrial DNA Copy Number and SIRT1 Expression in Porcine Oocytes

Relationship between mitochondrial DNA Copy Number and SIRT1 Expression in Porcine Oocytes

Mitochondrial biogenesis and degradation are induced by CCCP treatment of porcine oocytes

Segregation of Naturally Occurring Mitochondrial DNA Variants in a Mini-Pig Model

Contact Info

Product

Resources

About