The association of reproductive senescence with mitochondrial quantity, function, and DNA integrity in human oocytes at different stages of maturation

Duran, Eyup Hakan; Simsek-Duran, Fatma; Oehninger, Sergio; Jones, Howard W.; Castora, Frank J.

doi:10.1016/j.fertnstert.2011.05.056

Cited by 105 publications

(86 citation statements)

References 26 publications

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“…As mitochondrial function is essential for both oocyte and embryonic development (Cummins 2004, Eichenlaub-Ritter et al 2011), it appears that the significantly reduced functional mitochondria in the oocytes recovered from women of advanced reproductive age underlines the impairment of oocyte developmental competence (Madankumar et al 2003) by bioenergetic deficiencies, resulting in chromosomal segregation disorders (Schon et al 2000), failed maturation and fertilisation (Reynier et al 2001), and arrested cellular development (Van Blerkom 2011). However, our observation contrasts with a previous study (Duran et al 2011), which may be due to a difference in the mitochondrial assessment technique used.…”

Section: Discussioncontrasting

confidence: 99%

“…The number of mitochondria present in an oocyte may indicate the energetic status of the oocyte, which has been the aim for several investigations using different approaches and markers for estimating their numbers and/or mass quantity such as cytochrome c oxidase (Duran et al 2011, Eichenlaub-Ritter et al 2011. However, mitochondria are in a consistent dynamic turnover because of their short functional life span (Cummins 2004).…”

Section: Introductionmentioning

confidence: 99%

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A direct action for GH in improvement of oocyte quality in poor-responder patients

Weall¹,

Al-Samerria²,

Conceicao³

et al. 2015

Reproduction

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Declining female fecundity at later age and the increasing tendency for women to delay childbirth have lead to a drastic rise in the number of women seeking assisted reproductive technology. Many women fail to respond adequately to standard ovarian stimulation regimens, raising a significant therapeutic challenge. Recently, we have demonstrated that the administration of GH, as an adjunct to ovarian stimulation, has improved the clinical outcomes by enhancing the oocyte quality. However, the mechanism(s) by which GH facilitated this improvement is yet to be understood. This study aimed to determine these potential mechanism(s) through the use of immunofluorescent localisation of GH receptors (GHRs) on the human oocyte and unbiased computer-based quantification to assess and compare oocyte quality between women of varying ages, with or without GH treatment. This study demonstrates for the first time, the presence of GHRs on the human oocyte. The oocytes retrieved from older women showed significant decrease in the expression of GHRs and amount of functional mitochondria when compared with those from younger patients. More interestingly, when older patients were treated with GH, a significant increase in functional mitochondria was observed in their oocytes. We conclude that GH exerts a direct mode of action, enabling the improvement of oocyte quality observed in our previous study, via the upregulation of its own receptors and enhancement of mitochondrial activity. This result, together with recent observations, provides scientific evidence in support of the use of GH supplementation for the clinical management of poor ovarian response.

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Section: Discussioncontrasting

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A direct action for GH in improvement of oocyte quality in poor-responder patients

Weall¹,

Al-Samerria²,

Conceicao³

et al. 2015

Reproduction

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“…Furthermore, recent progress in real-time quantitative PCR technology has enabled sensitive analysis of mtDNA copy number in small sample volumes [195]. By this method mtDNA content is quantified relative to nDNA, yielding a mitochondrial-to-nuclear DNA ratio as measure of mtDNA copy number, which was used as a measure of mitochondrial content in animal and clinical studies [40,[196][197][198]. It should, however, be mentioned that changes in OXPHOS protein expression or mtDNA levels do not always correlate with changes in mitochondrial content (e.g.…”

Section: Biochemical Biomarkersmentioning

confidence: 99%

Regulation and Quantification of Cellular Mitochondrial Morphology and Content

Tronstad¹,

Nooteboom²,

Nilsson³

et al. 2014

CPD

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Running title: Regulation and quantification of mitochondrial morphology and content. Word count: 15,454 (total)Characters: 107,091 (including spaces); 92,067 (excluding spaces) Keywords: mitochondrial biogenesis, mitochondrial dynamics, mitochondrial degradation, living cells, TMRM, microscopy, segmentation, image analysis.Page 2 of 37 ABSTRACTMitochondria play a key role in signal transduction, redox homeostasis and cell survival, which extends far beyond their classical functioning in ATP production and energy metabolism. In living cells, mitochondrial content ("mitochondrial mass") depends on the cell-controlled balance between mitochondrial biogenesis and degradation. These processes are intricately linked to changes in net mitochondrial morphology and spatiotemporal positioning ("mitochondrial dynamics"), which are governed by mitochondrial fusion, fission and motility. It is becoming increasingly clear that mitochondrial mass and dynamics, as well as its ultrastructure and volume, are mechanistically linked to mitochondrial function and the cell. This means that proper quantification of mitochondrial morphology and content is of prime importance in understanding mitochondrial and cellular physiology in health and disease. This review first presents how cellular mitochondrial content is regulated at the level of mitochondrial biogenesis, degradation and dynamics. Next we discuss how mitochondrial dynamics and content can be analyzed with a special emphasis on quantitative live-cell microscopy strategies.

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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: 63%

“…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%

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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The association of reproductive senescence with mitochondrial quantity, function, and DNA integrity in human oocytes at different stages of maturation

Cited by 105 publications

References 26 publications

A direct action for GH in improvement of oocyte quality in poor-responder patients

A direct action for GH in improvement of oocyte quality in poor-responder patients

Regulation and Quantification of Cellular Mitochondrial Morphology and Content

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

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