Embryo developmental capability and pregnancy outcome are related to the mitochondrial DNA copy number and ooplasmic volume

Murakoshi, Yukitaka; Sueoka, Kou; Takahashi, Kaori; Sato, Suguru; Sakurai, Takeshi; Tajima, Hiroto; Yoshimura, Yasunori

doi:10.1007/s10815-013-0062-6

Cited by 117 publications

(92 citation statements)

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“…Mitochondrial DNA replication resumes around the time of blastocyst formation and is first observed in trophectoderm (TE) cells (reviewed in St John, 2014), consistent with the significant increase in the energy needs of the embryo associated with rapid cell proliferation and implantation (Van Blerkom, 2011). Mitochondrial replication, in turn, starts after implantation (Murakoshi et al., 2013; Pikó & Taylor, 1987). Mitochondrial DNA copy number is higher in aneuploid blastocysts (which contain an abnormal chromosome number) and in euploid blastocysts that fail to implant (Fragouli et al., 2015), suggesting that higher mtDNA copy number reflects embryonic stress and is associated with lower reproductive potential.…”

Section: Introductionmentioning

confidence: 99%

Mitochondrial unfolded protein response gene Clpp is required to maintain ovarian follicular reserve during aging, for oocyte competence, and development of pre‐implantation embryos

et al. 2018

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SummaryCaseinolytic peptidase P mediates degradation of unfolded mitochondrial proteins and activates mitochondrial unfolded protein response (mtUPR) to maintain protein homeostasis. Clpp −/− female mice generate a lower number of mature oocytes and two‐cell embryos, and no blastocysts. Clpp −/− oocytes have smaller mitochondria, with lower aspect ratio (length/width), and decreased expression of genes that promote fusion. A 4‐fold increase in atretic follicles at 3 months, and reduced number of primordial follicles at 6–12 months are observed in Clpp −/− ovaries. This is associated with upregulation of p‐S6, p‐S6K, p‐4EBP1 and p‐AKT473, p‐mTOR2481 consistent with mTORC1 and mTORC2 activation, respectively, and Clpp −/− oocyte competence is partially rescued by mTOR inhibitor rapamycin. Our findings demonstrate that CLPP is required for oocyte and embryo development and oocyte mitochondrial function and dynamics. Absence of CLPP results in mTOR pathway activation, and accelerated depletion of ovarian follicular reserve.

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Section: Introductionmentioning

confidence: 99%

Mitochondrial unfolded protein response gene Clpp is required to maintain ovarian follicular reserve during aging, for oocyte competence, and development of pre‐implantation embryos

et al. 2018

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“…Mitochondria are maternally inherited organelles that serve as the cell's powerhouses, using oxidative phosphorylation to supply ATP. Reproductive age is associated with a decrease in the amount of mitochondrial DNA (mtDNA) [5,6], and decreased mtDNA content leads to poor-quality oocytes and negative fertilization outcomes [7]. However, oocytes themselves cannot be used to predict fertilization outcome owing to ethical concerns.…”

Section: Introductionmentioning

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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“…Furthermore, the mitochondria and mtDNA copy number may be altered during cell differentiation and aging. It has also been reported in previous studies that the alteration of mtDNA participates in the regulation of ovarian function (5)(6)(7)(8). Therefore, it is likely that the dysfunction of the mitochondrion may be associated AA.…”

Section: Introductionmentioning

confidence: 64%

“…In addition, ovarian aging is associated with reduced oocyte mtDNA content and mitochondrial dysfunction (13). Numerous studies have reported that the mtDNA content in the oocytes of aged women or of women with a diminished ovarian reserve is significantly lower when compared with that of young patients or those with a normal ovarian reserve (6)(7)(8).…”

Section: Discussionmentioning

confidence: 99%

“…The mRNA expression levels of ND2 were detected by qPCR using the following primers: ND2, forward 5'-TTA TCC TCT TAT CCG TCC TC-3' and reverse 5'-TGT TAA GTC GAA GGG AGC-3'. The expression levels of genes were calculated using the 2 -ΔΔCq method (6). The relative ratio of the D-loop and GAPDH expression was used as the relative abundance of the mitochondrial genome.…”

Section: Analysis Of Mtdna Copy Number and Nadh Dehydrogenase Subunitmentioning

confidence: 99%

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Morphological and molecular variations induce mitochondrial dysfunction as a possible underlying mechanism of athletic amenorrhea

et al. 2017

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Abstract. Female athletes may experience difficulties in achieving pregnancy due to athletic amenorrhea (AA); however, the underlying mechanisms of AA remain unknown. The present study focuses on the mitochondrial alteration and its function in detecting the possible mechanism of AA. An AA rat model was established by excessive swimming. Hematoxylin and eosin staining, and transmission electron microscopic methods were performed to evaluate the morphological changes of the ovary, immunohistochemical examinations and radioimmunoassays were used to detect the reproductive hormones and corresponding receptors. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to test the mtDNA copy number. PCR and western blot analysis were used to test the expression of ND2. The change of morphological features of the rat ovaries revealed evident abnormalities. Particularly, the features of the mitochondria were markedly altered. In addition, reproductive hormones in the serum and tissues of AA rats were also detected to evaluate the function of the ovaries, and the levels of these hormones were significantly decreased. Furthermore, the mitochondrial DNA copy number (mtDNA) and expression of NADH dehydrogenase subunit 2 (ND2) were quantitated by qPCR or western blot analysis. Accordingly, the mtDNA copy number and expression of ND2 expression were markedly reduced in the AA rats. In conclusion, mitochondrial dysfunction in AA may affect the cellular energy supply and, therefore, result in dysfunction of the ovary. Thus, mitochondrial dysfunction may be considered as a possible underlying mechanism for the occurrence of AA. IntroductionAn increasing number of athletes are suffering from sports-associated diseases in the competitive sports. For professional female athletes, the incidence of athletic amenorrhea (AA) is particularly high, at a rate of 65-69% in athletes such as dancers and distance runners compared with 2-5% in normal women (1). The high AA in female athletes suggests that achieving pregnancy may be challenging. The current treatment methods primarily including increasing weight and decreasing exercise, replenishing vitamins and minerals, and reinforcing strength training (2). The normal menstrual cycle is regulated by the hypothalamic-pituitary-ovarian axis, and the ovary is one of the most important organs in this axis (3). Thus, it is important to investigate the underlying mechanism of ovary dysfunction in AA.The mitochondrion is the organelle of energy supply in eukaryotic organisms. Mitochondrial abnormity or dysfunction has been reported to be involved in various diseases (4). To some of these diseases, the dysfunction of mitochondrion is considered as a key mechanism to cause the dysfunction of the organ, thus it was conjectured that the dysfunction of mitochondrion may cause the dysfunction of ovary, which may result in AA. The number of mitochondria and the mitochondrial DNA (mtDNA) copy number may vary among different types of cells and tissues. Furthermore, the mitochondria an...

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Embryo developmental capability and pregnancy outcome are related to the mitochondrial DNA copy number and ooplasmic volume

Cited by 117 publications

References 50 publications

Mitochondrial unfolded protein response gene Clpp is required to maintain ovarian follicular reserve during aging, for oocyte competence, and development of pre‐implantation embryos

Mitochondrial unfolded protein response gene Clpp is required to maintain ovarian follicular reserve during aging, for oocyte competence, and development of pre‐implantation embryos

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

Morphological and molecular variations induce mitochondrial dysfunction as a possible underlying mechanism of athletic amenorrhea

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