Resveratrol protects against age-associated infertility in mice

Liu, Mengyuan; Yin, Yu; Ye, Xiaoying; Zeng, Ming; Zhao, Qiang; Keefe, David L.; Liu, Lin

doi:10.1093/humrep/des437

Cited by 243 publications

(212 citation statements)

References 66 publications

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“…Moreover, resveratrol has been reported to have several effects in reproductive physiology, such as the maintenance of ovarian reserve (32) or a protective role in aging-related infertility (33). Likewise, the therapeutic potential of resveratrol in the treatment of PCOS has been postulated because this polyphenol promotes apoptosis (34) and reduces androgen synthesis (35) in ovarian theca cells.…”

mentioning

confidence: 99%

Effects of resveratrol on ovarian response to controlled ovarian hyperstimulation in ob/ob mice

Cabello¹,

Garrido²,

Morán³

et al. 2015

Fertility and Sterility

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mentioning

confidence: 99%

Effects of resveratrol on ovarian response to controlled ovarian hyperstimulation in ob/ob mice

Cabello¹,

Garrido²,

Morán³

et al. 2015

Fertility and Sterility

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“…Also, RSV treatment resulted in an increase of telomerase activity, telomere length, and age-related gene expression of Sirt1 which was reported to increase telomerase activity, and a decrease of the senescence marker p21 in ovaries, similar to those of young mice (2~3-months-old) [338].…”

Section: Reproductive System Diseasesmentioning

confidence: 74%

The pharmacology of resveratrol in animals and humans

Park

Pezzuto

2015

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

258

193

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In addition to thousands of research papers related to resveratrol (RSV), approximately 300 review articles have been published. Earlier research tended to focus on pharmacological activities of RSV related to cardiovascular systems, inflammation, and carcinogenesis/cancer development. More recently, the horizon has been broadened by exploring the potential effect of RSV on the aging process, diabetes, neurological dysfunction, etc. Herein, we primarily focus on the in vivo pharmacological effects of RSV reported over the past 5 years (2009-2014). In addition, recent clinical intervention studies performed with resveratrol are summarized. Some discrepancies exist between in vivo studies with animals and clinical studies, or between clinical studies, which are likely due to disparate doses of RSV, experimental settings, and subject variation. Nevertheless, many positive indications have been reported with mammals, so it is reasonable to advocate for the conduct of more definitive clinical studies. Since the safety profile is pristine, an added advantage is the use of RSV as a dietary supplement. This article is part of a Special Issue entitled: Resveratrol: Challenges in translating pre-clinical findings to improved patient outcomes.

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“…Extensive evidence shows that reactive oxidative stress induces DNA damage, reduces fertility [59] and contributes to telomere attrition [60]. Anti-oxidants reduce DNA damage and delay ovarian aging [45,61], but it remains to be determined whether anti-oxidants delay ovarian aging in primate monkeys. Elevated DNA repair capacity from increased expression of BRCA1 in middle age might help repair telomeres and slow telomere shortening.…”

Section: Discussionmentioning

confidence: 99%

“…Sections were co-immunostained with γH2AX and TRF2 or BRCA1, and analyzed for the number of foci in different cells. Follicles were classified into different category depending on their developmental stages [45]. Primordial, primary and intermediate-stage (compact or enlarged oocyte with a single layer of mixed flattened and cuboidal granulosa cells) follicles were identified by the presence of an oocyte surrounded by a single layer of flat, squamous or cuboidal granulosa cells.…”

Section: Foci Countsmentioning

confidence: 99%

Increased DNA damage and repair deficiency in granulosa cells are associated with ovarian aging in rhesus monkey

Zhang

Zeng

et al. 2015

J Assist Reprod Genet

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Purpose Ovarian aging is closely tied to the decline in ovarian follicular reserve and oocyte quality. During the prolonged reproductive lifespan of the female, granulosa cells connected with oocytes play critical roles in maintaining follicle reservoir, oocyte growth and follicular development. We tested whether double-strand breaks (DSBs) and repair in granulosa cells within the follicular reservoir are associated with ovarian aging. Methods Ovaries were sectioned and processed for epifluorescence microscopy, confocal microscopy, and immunohistochemistry. DNA damage was revealed by immunstaining of γH2AX foci and telomere damage by γH2AX foci colocalized with telomere associated protein TRF2. DNA repair was indicated by BRCA1 immunofluorescence.Results DSBs in granulosa cells increase and DSB repair ability, characterized by BRCA1 foci, decreases with advancing age. γH2AX foci increase in primordial, primary and secondary follicles with advancing age. Likewise, telomere damage increases with advancing age. In contrast, BRCA1 foci in granulosa cells of primordial, primary and secondary follicles decrease with monkey age. BRCA1 positive foci in the oocyte nuclei also decline with maternal age. Conclusions Increased DSBs and reduced DNA repair in granulosa cells may contribute to ovarian aging. Discovery of therapeutics that targets these pathways might help maintain follicle reserve and postpone ovarian dysfunction with age.

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Resveratrol protects against age-associated infertility in mice

Abstract: This work was supported by MOST of China National Basic Research Program (grant number: 2010CB94500 and 2012CB911200). The authors have no competing interests to declare.

Cited by 243 publications

References 66 publications

Effects of resveratrol on ovarian response to controlled ovarian hyperstimulation in ob/ob mice

Effects of resveratrol on ovarian response to controlled ovarian hyperstimulation in ob/ob mice

The pharmacology of resveratrol in animals and humans

Increased DNA damage and repair deficiency in granulosa cells are associated with ovarian aging in rhesus monkey

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