Can Coenzyme Q10 supplementation protect the ovarian reserve against oxidative damage?

Özcan, Pınar; Fıçıcıoğlu, Cem; Kızılkale, Özge; Yeşiladalı, Mert; Tok, Olgu Enis; Özkan, Ferda; Eşrefoğlu, Mukaddes

doi:10.1007/s10815-016-0751-z

Cited by 68 publications

(70 citation statements)

References 36 publications

(40 reference statements)

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“…As a result, a potent method to protect ovarian function would provide great benefits for patients and physicians. Many studies addressed the protection of ovarian function during cisplatin chemotherapy, but most of them involved antioxidants, such as coenzyme Q10, colony stimulating factor, sphingosine‐1‐phosphate, and erythropoietin (Akdemir et al, 2014; Dayangan Sayan et al, 2017; Li et al, 2014; Özcan et al, 2016; Roness, Kashi, & Meirow, 2016). However, the efficacy and specific mechanism of these drugs are unknown.…”

Section: Discussionmentioning

confidence: 99%

Rapamycin preserves the primordial follicle pool during cisplatin treatment in vitro and in vivo

Xie

Zhou

et al. 2020

Molecular Reproduction Devel

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Rapamycin has been proven to effectively inhibit the activation of primordial follicles while cisplatin-induced the loss of primordial follicles due to the overactivation of the primordial follicle stockpile. Whether rapamycin could inhibit the loss of primordial follicles induced by cisplatin is still unknown. The ovaries of neonatal Sprague Dawley rats were cultured in vitro in different doses of rapamycin (0.08, 0.16, and 0.32 μg/ml) and cisplatin (0.1, 0.4, and 0.8 μg/ml). The immature BALB/c mice were administered cisplatin with or without rapamycin by intraperitoneal injection. Ovaries were collected to analyze the histomorphology, the messenger RNA (mRNA) expression of anti-Mullerian hormone (AMH), growth differentiation factor 9 (GDF9), and bone morphogenetic protein 15 (BMP15) and the expression of key proteins of mammalian target of rapamycin (mTOR) pathway.Growing follicle counts of ovaries cultured in vitro in the R0.16 and R0.32 groups were decreased and the ratio of growing to primordial follicles was also decreased in a dose-dependent manner. In the C0.8 group, growing follicles were decreased compared with the other groups while the ratio was substantially increased in the C0.4 and C0.8 group. Co-treatment attenuated primordial follicle loss and reduced the upregulated ratio induced by cisplatin. Ovarian follicle dynamics in vivo was consistent with the in vitro results. Primordial follicles counts were statistically increased and the ratio was reduced in the rapamycin group compared with the control group. Primordial follicle counts were dramatically reduced in the cisplatin group whereas co-treatment with rapamycin slightly recovered its counts. There was no obvious difference in the number of growing follicles between the cisplatin group and other groups. The ratio was significantly increased in cisplatin-treated mice whereas decreased in the co-treatment group. The apoptosis rate of antral follicles in cisplatin-treated mice was higher than the other groups while the apoptosis rate was decreased in the co-treatment group in vivo. Compared with the control and rapamycin group, the mRNA expression of AMH, GDF9, and BMP15 were Abbreviations: AMH, anti-Mullerian hormone; BMP15, bone morphogenetic protein 15; CCK-8, cell counting kit-8; con, control group; FBS, fetal bovine serum; GDF9, growth differentiation factor 9; HE, hematoxylin and eosin; mTOR, mammalian target of rapamycin; mTORC1, mammalian target of rapamycin complex 1; PBS, phosphate-buffered solution; PFA, paraformaldehyde; POI, premature ovarian insufficiency; PTEN, phosphate and tension homology deleted on chromosome ten; qPCR, quantitative polymerase chain reaction; TSC1/TSC2, tuberous sclerosis complex; TUNEL, terminal deoxynucleotidyl transferase-mediated nick end labeling assay. downregulated in the cisplatin group. The co-treatment group recovered the mRNA expression of BMP15. In addition, the expression of key protein of mTOR pathway rpS6 and its phosphorylated forms were increased in the cisplatin-treated group while co-treatme...

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Section: Discussionmentioning

confidence: 99%

Rapamycin preserves the primordial follicle pool during cisplatin treatment in vitro and in vivo

Xie

Zhou

et al. 2020

Molecular Reproduction Devel

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“…Moreover, previous literatures indicated that when ovary is exposed to some drugs related to oxidative stress, such as chemotherapeutic drugs, gamma irradiation, or polycyclic aromatic hydrocarbons, loss of primordial follicles is induced. However, the mechanism of reactive oxygen species (ROS) causing primordial follicle depletion is not fully clear yet [ 17 – 19 ]. The mechanisms by which anticancer drugs exert cytotoxicity are diverse, and include the promotion of ROS generation.…”

Section: Introductionmentioning

confidence: 99%

Protective effects of mangafodipir against chemotherapy-induced ovarian damage in mice

Qin

Iwase

Murase

et al. 2018

Reprod Biol Endocrinol

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BackgroundGiven the seriousness of chemotherapy-induced ovarian injury in female cancer patients, the preservation of fertility, including through the use of cryopreservation technology and pharmaceuticals, requires investigation. Previous studies have shown that damage to the ovaries is related to oxidative stress caused by anticancer drugs. Therefore, superoxide dismutase (SOD) may represent a key factor in the pharmacological protection of the ovaries. The aim of our study was to identify the effects of mangafodipir, a manganese chelate and SOD-mimetic, on suppression of apoptosis in granulosa cells and primordial follicle activation induced by anticancer drugs.MethodsCell viability assays using methyltrichlorosilane solutions and immunoblotting for cleaved caspase-3 were performed in in vitro experiments with the simultaneous addition of mangafodipir to human non-luteinized granulosa cell line (HGrC) cultures treated with hydrogen peroxide (H2O2), cisplatin, or paclitaxel. Count and morphological analyses of follicles at each developing stage in the ovaries and immunohistochemistry for cleaved caspase-3, Ki67 and 4-hydroxynonenal, a marker for oxidative stress, were also performed using mangafodipir-injected 6-week-old female ICR mice treated with cisplatin or paclitaxel. Further, mangafodipir was injected into 6-week-old female BALB/c mice inoculated with ES-2 to analyze whether mangafodipir inhibits the anti-tumor effects of cisplatin or paclitaxel treatment.ResultsMangafodipir attenuated apoptosis induced by H2O2 and anticancer drugs in vitro. Mangafodipir also decreased the expression of 4-hydroxynonenal and reduced cisplatin- and paclitaxel-induced apoptosis in granulosa cells in vivo. In addition, mangafodipir inhibited the loss of primordial follicles. Tumor xenograft studies in mice showed that mangafodipir did not affect anticancer drug antitumor effects.ConclusionsOxidative stress might be one of the mechanisms of cisplatin- and paclitaxel-induced the loss of primordial follicles. Mangafodipir can reduce cisplatin- and paclitaxel-induced apoptosis in granulosa cells and primordial follicle activation partially via its SOD activity. At the same time, mangafodipir might have other potential mechanisms to inhibit the activation of primordial follicles. Further, mangafodipir attenuated the ovarian damage caused by cisplatin and paclitaxel without affecting their antitumor activities. Mangafodipir, therefore, though its efficacy might be limited, may be a new option for the preservation of fertility during anticancer treatment.

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“…Although shown to be beneficial in treating male oligo-asthenospermia and in cardiology, the clinical use in POR is not abundant (98)(99)(100)(101). Preclinical studies in animals have suggested CoQ10 can protect ovarian reserve, possibly counteracting the physiological ovarian aging by restoring mitochondrial function and augmenting embryo cleavage and blastocyst generation (102)(103)(104). In female infertility, CoQ10 supplementation to COH improved patients' response to ovulation induction and decreased fetal aneuploidy in older patients, between age 35 and 43 (105,106).…”

Section: Coenzyme Q10mentioning

confidence: 99%

What Is the Best Regimen for Ovarian Stimulation of Poor Responders in ART/IVF?

Blumenfeld

2020

Front. Endocrinol.

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The infertile patients with aging ovaries-also sometimes referred to as impending premature ovarian insufficiency (POI), impending premature ovarian failure (POF), or poor ovarian responders (POR), constitute a significant and increasing bulk of the patients appealing to IVF/ART. Different causes have been cited in the literature, among the identified etiologies, including chromosomal and genetic etiology, metabolic, enzymatic, iatrogenic, toxic, autoimmune, and infectious causes. Although the most successful and ultimate treatment of POI/POF/POR patients is egg donation (ED), many, if not most, of these infertile women are reluctant to consent to ED upon the initial diagnostic interview, requesting alternative solutions despite the low odds for success. Despite anecdotal case reports, no unequivocal treatment proved to be successful for these patients in prospective randomized controlled trials. Nevertheless, the addition of growth hormone (GH) to ovarian stimulation in POR with GH deficiency may improve the results of controlled ovarian hyperstimulation (COH) and the IVF success. In patients with autoimmune etiology for POR/POI, the combination of glucocorticosteroids, pituitary-ovarian suppression, and COH may be successful in achieving the desired conception.

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Can Coenzyme Q10 supplementation protect the ovarian reserve against oxidative damage?

Cited by 68 publications

References 36 publications

Rapamycin preserves the primordial follicle pool during cisplatin treatment in vitro and in vivo

Rapamycin preserves the primordial follicle pool during cisplatin treatment in vitro and in vivo

Protective effects of mangafodipir against chemotherapy-induced ovarian damage in mice

What Is the Best Regimen for Ovarian Stimulation of Poor Responders in ART/IVF?

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