Ovarian ageing: the role of mitochondria in oocytes and follicles

May‐Panloup, Pascale; Boucret, Lisa; Barca, Juan Manuel Chao de la; Desquiret-Dumas, Valérie; Ferré-L’Hôtellier, Véronique; Morinière, Catherine; Descamps, Philippe; Procaccio, Vincent; Reynier, Pascal

doi:10.1093/humupd/dmw028

Cited by 423 publications

(324 citation statements)

References 279 publications

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“…Alterations in the mtDNA, which are reflected by the change of its copy number and its mutation, have been reported to be involved in a series of diseases and in organ dysfunction (4). Several studies have reported that the alterations of mtDNA are involved in the maturity, aging and lesion formation in the ovary (12,13). Mutations in mtDNA can cause the abnormally expression of oxidative phosphorylation complex and abnormal transfer RNAs, which may be associated with polycystic ovarian syndrome patients (12).…”

Section: Discussionmentioning

confidence: 99%

“…Devine et al (14) also reported that ~20% of patients consulting for infertility presented signs of premature ovarian aging. 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%

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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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Section: Discussionmentioning

confidence: 99%

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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“…112 Subsequently, more than 50 successful live births have been achieved with this method. 113 However, due to lack of adequate experimental data and the potential risk associated with the transmission thirdparty genetic material, the US Food and Drug Administration (FDA)…”

Section: Mitochondrial Transfermentioning

confidence: 99%

Mitochondrial dysfunction and ovarian aging

Wang

Zhang

Jiang

et al. 2017

American J Rep Immunol

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Mitochondria are double‐membrane‐bound organelles that are responsible for the generation of most of the cell's energy. Mitochondrial dysfunction has been implicated in cellular senescence in general and ovarian aging in particular. Recent studies exploited this association by studying mitochondrial DNA (mtDNA) copy number as a potential biomarker of embryo viability and the use of mitochondrial nutrients and autologous mitochondrial transfer as a potential treatment for poor ovarian function and response.

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“…If any disorder occurs in any part of the process of mutual regulation between granulosa cells and oocytes, it will interfere with the reproductive process and further affect reproduction (Nagyova, Kalous, & Nemcova, ). Although the emergence of assisted reproductive technology (ART) has made great progress in the treatment of infertility, some infertility patients are still unable to obtain offspring through ART (Chen & Zhou, ; Giuliani et al, ; May‐Panloup et al, ). One of the main reasons is that the molecular mechanism of the interaction between granulosa cells and oocytes is not completely understood (Chang, Qiao, & Leung, ).…”

Section: Introductionmentioning

confidence: 99%

LncRNA Gm2044 promotes 17β‐estradiol synthesis in mpGCs by acting as miR‐138‐5p sponge

Ren

et al. 2019

Molecular Reproduction Devel

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Long noncoding RNAs (lncRNAs) have been demonstrated to play vital roles in mammalian reproduction. Our previous research revealed that lncRNA Gm2044 is highly expressed in mouse spermatocytes and regulates male germ cell function. The gene annotation database BioGPS shows that Gm2044 is not only highly expressed in testicular tissue but also in ovarian tissue, which suggests that Gm2044 may be involved in female reproductive development. In this study, we confirmed that lncRNA Gm2044 promotes 17β‐estradiol synthesis in mouse pre‐antral follicular granulosa cells (mpGCs). Furthermore, bioinformatics methods, western blot, and the luciferase assay proved that Gm2044 functions as a miR‐138‐5p sponge to inhibit the direct target of miR‐138‐5p, Nr5a1, which enhances 17β‐estradiol synthesis through cyp19a1 activation. Taken together, our results provide an insight into the mechanistic roles of lncRNA Gm2044 for 17β‐estradiol synthesis by acting as competing‐endogenous RNAs to modulate the function of mpGCs. Studying the potential lncRNAs, which regulate estradiol release, will be beneficial for the diagnosis and treatment of steroid hormone‐related disease.

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Ovarian ageing: the role of mitochondria in oocytes and follicles

Abstract: A fuller understanding of the involvement of mitochondria in cases of infertility linked to ovarian ageing would contribute to a better management of the disorder in the future.

Cited by 423 publications

References 279 publications

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

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

Mitochondrial dysfunction and ovarian aging

LncRNA Gm2044 promotes 17β‐estradiol synthesis in mpGCs by acting as miR‐138‐5p sponge

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