The antioxidant curcumin postpones ovarian aging in young and middle-aged mice

2020 ◽  
Vol 32 (3) ◽  
pp. 292 ◽  
Author(s):  
Saeideh Hasani Azami ◽  
Hamid Nazarian ◽  
Mohammad Amin Abdollahifar ◽  
Fatemeh Eini ◽  
Mehdi Allahbakhshian Farsani ◽  
...  
Keyword(s):  
Serum Levels ◽  
Oocyte Quality ◽  
Sirtuin 1 ◽  
Ovarian Volume ◽  
Ovarian Aging ◽  
Morphogenetic Protein ◽  
Growth Differentiation Factor 9 ◽  
Oocyte Aging ◽  
Old Mice

Reproductive senescence is accompanied by a reduced number and quality of ovarian follicles in response to the accumulation of free radicals and the process of apoptosis. Having selected mice as models, we examined the hypothesis that curcumin as an antioxidant and anti-inflammatory agent might prevent or retard ovarian aging. Female NMRI 21-day-old mice were divided into control, vehicle and curcumin groups. In the treatment group the mice received curcumin at 100mgkg–1day–1 intraperitoneally. After 6, 12 and 33 weeks several parameters were examined including ovarian reserve, oocyte quality, oxidative status, invitro fertilisation and expression of ovulation-related (growth differentiation factor 9 (GDF-9) and bone morphogenetic protein 15 (BMP-15)) and anti-aging-related (sirtuin 1 (SIRT-1) and SIRT-3) genes. Curcumin treatment up to 12 and 33 weeks resulted in increased ovarian volume and number of follicles and was associated with elevated anti-Müllerian hormone and oestrogen and diminished FSH serum levels. Furthermore, enhanced oocyte maturation, fertilisation and embryo development plus reduced oxidative stress were seen in the curcumin group. Also, the expression of GDF-9, BMP-15, SIRT-1 and SIRT-3 genes was increased in the curcumin group. Concerning gestational age, the findings of the study suggested that administration of curcumin could delay the process of oocyte aging in a mouse model.

scholarly journals BRCA-related ATM-mediated DNA double-strand break repair and ovarian aging

2019 ◽  
Vol 26 (1) ◽  
pp. 43-57 ◽  
Author(s):  
Volkan Turan ◽  
Kutluk Oktay
Keyword(s):  
Clinical Evidence ◽  
Strand Break ◽  
Oocyte Quality ◽  
Repair Pathway ◽  
Dsb Repair ◽  
Ovarian Aging ◽  
Age Related ◽  
Dna Double Strand Break ◽  
Targeted Treatments ◽  
Oocyte Aging

Abstract BACKGROUND Oocyte aging has significant clinical consequences, and yet no treatment exists to address the age-related decline in oocyte quality. The lack of progress in the treatment of oocyte aging is due to the fact that the underlying molecular mechanisms are not sufficiently understood. BRCA1 and 2 are involved in homologous DNA recombination and play essential roles in ataxia telangiectasia mutated (ATM)-mediated DNA double-strand break (DSB) repair. A growing body of laboratory, translational and clinical evidence has emerged within the past decade indicating a role for BRCA function and ATM-mediated DNA DSB repair in ovarian aging. OBJECTIVE AND RATIONALE Although there are several competing or complementary theories, given the growing evidence tying BRCA function and ATM-mediated DNA DSB repair mechanisms in general to ovarian aging, we performed this review encompassing basic, translational and clinical work to assess the current state of knowledge on the topic. A clear understanding of the mechanisms underlying oocyte aging may result in targeted treatments to preserve ovarian reserve and improve oocyte quality. SEARCH METHODS We searched for published articles in the PubMed database containing key words, BRCA, BRCA1, BRCA2, Mutations, Fertility, Ovarian Reserve, Infertility, Mechanisms of Ovarian Aging, Oocyte or Oocyte DNA Repair, in the English-language literature until May 2019. We did not include abstracts or conference proceedings, with the exception of our own. OUTCOMES Laboratory studies provided robust and reproducible evidence that BRCA1 function and ATM-mediated DNA DSB repair, in general, weakens with age in oocytes of multiple species including human. In both women with BRCA mutations and BRCA-mutant mice, primordial follicle numbers are reduced and there is accelerated accumulation of DNA DSBs in oocytes. In general, women with BRCA1 mutations have lower ovarian reserves and experience earlier menopause. Laboratory evidence also supports critical role for BRCA1 and other ATM-mediated DNA DSB repair pathway members in meiotic function. When laboratory, translational and clinical evidence is considered together, BRCA-related ATM-mediated DNA DSB repair function emerges as a likely regulator of ovarian aging. Moreover, DNA damage and repair appear to be key features in chemotherapy-induced ovarian aging. WIDER IMPLICATIONS The existing data suggest that the BRCA-related ATM-mediated DNA repair pathway is a strong candidate to be a regulator of oocyte aging, and the age-related decline of this pathway likely impairs oocyte health. This knowledge may create an opportunity to develop targeted treatments to reverse or prevent physiological or chemotherapy-induced oocyte aging. On the immediate practical side, women with BRCA or similar mutations may need to be specially counselled for fertility preservation.

scholarly journals Melatonin attenuates postovulatory oocyte dysfunction by regulating SIRT1 expression

Reproduction ◽  
2018 ◽  
Vol 156 (1) ◽  
pp. 81-92 ◽  
Author(s):  
Qingling Yang ◽  
Shanjun Dai ◽  
Xiaoyan Luo ◽  
Jing Zhu ◽  
Fangyuan Li ◽  
...  
Keyword(s):  
Aging Process ◽  
Oocyte Quality ◽  
Developmental Competence ◽  
Oocyte Aging ◽  
Sirt1 Inhibitor ◽  
Underlying Mechanisms ◽  
Related Proteins ◽  
Sirt1 Activator

The quality of postovulatory metaphase II oocytes undergoes a time-dependent deterioration as a result of the aging process. Melatonin is considered to be an anti-aging agent. However, the underlying mechanisms of how melatonin improves the quality of postovulatory aged oocytes remain largely unclear. In this study, by using mouse model, we found that there were elevated reactive oxygen species levels and impaired mitochondrial function demonstrated by reduced mitochondrial membrane potential and increased mitochondrial aggregation in oocytes aged 24 h, accompanied by an increased number of meiotic errors, unregulated autophagy-related proteins and early apoptosis, which led to decreased oocyte quality and disrupted developmental competence. However, all of these events can be largely prevented by supplementing the oocyte culture medium with 10−3 M melatonin. Additionally, we found that the expression of sirtuin family members (SIRT1, 2 and 3) was dramatically reduced in aged oocytes. In addition,in vitrosupplementation with melatonin significantly upregulated the expression of SIRT1 and antioxidant enzyme MnSOD, but this action was not observed for SIRT2 and SIRT3. Furthermore, the protective effect of melatonin on the delay of oocyte aging vanished when the SIRT1 inhibitor EX527 was used to simultaneously treat the oocytes with melatonin. Consistent with this finding, we found that the postovulatory oocyte aging process was markedly attenuated when the oocytes were treated with the SIRT1 activator SRT1720. In conclusion, our data strongly indicate that melatonin delays postovulatory mouse oocyte aging via a SIRT1–MnSOD-dependent pathway, which may provide a molecular mechanism support for the further application of melatonin in the assisted reproductive technology field.

Melatonin enhances the in vitro maturation and developmental potential of bovine oocytes denuded of the cumulus oophorus

Zygote ◽  
2014 ◽  
Vol 23 (4) ◽  
pp. 525-536 ◽  
Author(s):  
Xue-Ming Zhao ◽  
Jiang-Tao Min ◽  
Wei-Hua Du ◽  
Hai-Sheng Hao ◽  
Yan Liu ◽  
...  
Keyword(s):  
Formation Rate ◽  
Developmental Rate ◽  
Mrna Levels ◽  
Developmental Potential ◽  
Cumulus Oophorus ◽  
Morphogenetic Protein ◽  
Growth Differentiation Factor 9 ◽  
Bovine Oocytes

SummaryThis study was designed to determine the effect of melatonin on the in vitro maturation (IVM) and developmental potential of bovine oocytes denuded of the cumulus oophorus (DOs). DOs were cultured alone (DOs) or with 10−9 M melatonin (DOs + MT), cumulus–oocyte complexes (COCs) were cultured without melatonin as the control. After IVM, meiosis II (MII) rates of DOs, and reactive oxygen species (ROS) levels, apoptotic rates and parthenogenetic blastocyst rates of MII oocytes were determined. The relative expression of ATP synthase F0 Subunit 6 and 8 (ATP6 and ATP8), bone morphogenetic protein 15 (BMP-15) and growth differentiation factor 9 (GDF-9) mRNA in MII oocytes and IFN-tau (IFN-τ), Na+/K+-ATPase, catenin-beta like 1 (CTNNBL1) and AQP3 mRNA in parthenogenetic blastocysts were quantified using real-time polymerase chain reaction (PCR). The results showed that: (1) melatonin significantly increased the MII rate of DOs (65.67 ± 3.59 % vs. 82.29 ± 3.92%; P < 0.05), decreased the ROS level (4.83 ± 0.42 counts per second (c.p.s) vs. 3.78 ± 0.29 c.p.s; P < 0.05) and apoptotic rate (36.99 ± 3.62 % vs. 21.88 ± 2.08 %; P < 0.05) and moderated the reduction of relative mRNA levels of ATP6, ATP8, BMP-15 and GDF-9 caused by oocyte denudation; (2) melatonin significantly increased the developmental rate (24.17 ± 3.54 % vs. 35.26 ± 4.87%; P < 0.05), and expression levels of IFN-τ, Na+/K+-ATPase, CTNNBL1 and AQP3 mRNA of blastocyst. These results indicated that melatonin significantly improved the IVM quality of DOs, leading to an increased parthenogenetic blastocyst formation rate and quality.

scholarly journals Serum Concentrations of GDF9 and BMP15 Across the Menstrual Cycle

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A734-A735
Author(s):  
Angelique Helena Riepsamen ◽  
Mark W Donoghoe ◽  
Angela Baerwald ◽  
Michael W Pankhurst ◽  
Shelly Lien ◽  
...  
Keyword(s):  
Menstrual Cycle ◽  
Generalized Additive Model ◽  
Additive Model ◽  
Oocyte Quality ◽  
Serum Concentrations ◽  
Morphogenetic Protein ◽  
Late Luteal Phase ◽  
Growth Differentiation Factor 9 ◽  
Reproductive Life ◽  
Frequent Sampling

Abstract Growth differentiation factor-9 (GDF9) and bone morphogenetic protein-15 (BMP15) are TGF-β proteins that regulate key processes throughout folliculogenesis and are determinants of mammalian fecundity (1). They are uniquely produced predominantly by the oocyte and have potential clinical application as markers of oocyte quality and quantity (2). However, no studies have been conducted to assess whether serum concentrations alter across the different phases of the menstrual cycle, and thus if assessment should be confined to specific cycle stages. The aim of this study was to measure serum concentrations of these proteins during the menstrual cycle in women at different stages of reproductive life. Serum was collected every 1-3 days throughout the menstrual cycle from 41 healthy ovulatory women from three cohorts: menses to late luteal phase (21-29 years of age; n=16; University of Otago) and across one interovulatory interval (18-35 years of age; n=10; and 45-50 years of age; n=15; University of Saskatchewan), with simultaneous ultrasound scans confirming ovulation. Serum concentrations of GDF9, BMP15, estradiol, FSH, LH, progesterone, inhibin A and B and AMH were measured. GDF9 and BMP15 were detectable in 54% and 73% of women and varied 236- and 52-fold between women, respectively. To detect changes, mean concentrations and variances across the cycle were statistically modelled using a generalized additive model of location, shape and scale (GAMLSS). Across the menstrual cycle, there were minimal changes in serum GDF9 or BMP15 within a woman for all cohorts, with no significant differences detected in modelled mean concentrations. However, modelled variances were highest in the luteal phases of all women for BMP15 immediately following ovulation, regardless of age, suggesting a possible underlying cyclic pattern. These results suggest that serum BMP15 and GDF9 are not overtly affected by menstrual cycle dynamics but may be more stable in the follicular phase. Larger studies with more frequent sampling should establish if BMP15 and presumably GDF9 demonstrate clinically relevant cyclic variation. References: (1) Gilchrist RB et al., HRU 2008; 14:159-77. (2) Riepsamen AH et al., Endocrinol 2019; 160:2298-313.

scholarly journals Inositol and In Vitro Fertilization with Embryo Transfer

2017 ◽  
Vol 2017 ◽  
pp. 1-5 ◽  
Author(s):  
G. Simi ◽  
A. R. Genazzani ◽  
M. E. R. Obino ◽  
F. Papini ◽  
S. Pinelli ◽  
...  
Keyword(s):  
In Vitro Fertilization ◽  
Ovarian Function ◽  
Serum Levels ◽  
Oocyte Quality ◽  
Fertilization Program ◽  
Hormonal Responses ◽  
Vitro Fertilization ◽  
Infertile Patients

Recently, studies on inositol supplementation during in vitro fertilization program (IVF) have gained particular importance due to the effect of this molecule on reducing insulin resistance improving ovarian function, oocyte quality, and embryo and pregnancy rates and reducing gonadotropin amount during stimulation. Inositol and its isoforms, especially myoinositol (MYO), are often used as prestimulation therapy in infertile patients undergoing IVF cycle. Inositol supplementation started three months before ovarian stimulation, resulting in significant improvements in hormonal responses, reducing the amount of FSH necessary for optimal follicle development and serum levels of 17beta-estradiol measured the day of hCG injection. As shown by growing number of trials, MYO supplementation improves oocyte quality by reducing the number of degenerated and immature oocytes, in this way increasing the quality of embryos produced. Inositol can also improve the quality of sperm parameters in those patients affected by oligoasthenoteratozoospermia.

scholarly journals Theaflavin 3, 3 ′ -Digallate Delays Ovarian Aging by Improving Oocyte Quality and Regulating Granulosa Cell Function

2021 ◽  
Vol 2021 ◽  
pp. 1-18
Author(s):  
Jiahuan He ◽  
Guidong Yao ◽  
Qina He ◽  
Tongwei Zhang ◽  
Huiying Fan ◽  
...  
Keyword(s):  
Granulosa Cell ◽  
High Throughput Sequencing ◽  
Ovarian Function ◽  
Antioxidant Properties ◽  
Life Quality ◽  
Oocyte Quality ◽  
Physiological Age ◽  
Female Reproduction ◽  
Ovarian Aging

Ovarian aging refers to the gradual decline of ovarian function with increasing physiological age, manifested as decreased ovarian reserve, elevated aging-related markers, and reduced oocyte quality. With a declining female fertility and a growing aging population, it is urgent to delay ovarian aging to maintain fertility and improve the life quality of women. Theaflavin 3, 3 ′ -digallate (TF3) is a naturally bioactive polyphenol compound extracted from black tea, and its antioxidant properties play an important role in maintaining human health and delaying aging; however, the effects of TF3 on female reproduction and ovarian function are not yet clear. Here, we show that TF3 can preserve primordial follicle pool, partially restore the estrous cycle, and increase the offspring number of aged mice. Meanwhile, TF3 gavage increased the number of oocytes retrieved, decreased the level of reactive oxygen species, increased the level of glutathione, and decreased the abnormal rate of oocyte spindle after ovulation induction. Moreover, TF3 inhibited human granulosa cell apoptosis and improved their antioxidative stress ability. High-throughput sequencing and small-molecule-targeted pharmacological prediction show that TF3 affects multiple pathways and gene expression levels, mainly involved in reproductive and developmental processes. It may also affect cellular function by targeting mTOR to regulate the autophagic pathway, thereby delaying the process of ovarian aging. This study shows that TF3 can be used as a potential dietary supplement to protect ovary function from aging and thereby improving the life quality of advanced-age women.

scholarly journals Ceramide and mitochondrial function in aging oocytes: joggling a new hypothesis and old players

Reproduction ◽  
2012 ◽  
Vol 143 (1) ◽  
pp. 1-10 ◽  
Author(s):  
Loro L Kujjo ◽  
Gloria I Perez
Keyword(s):  
Molecular Mechanisms ◽  
Oocyte Quality ◽  
Developmental Potential ◽  
Present Information ◽  
Molecular Determinants ◽  
Oocyte Aging ◽  
And Function ◽  
Maternal Aging ◽  
New Hypothesis

Maternal aging adversely affects oocyte quality (function and developmental potential) and consequently lowers pregnancy rates while increasing spontaneous abortions. Substantial evidence, especially from egg donation studies, implicates the decreased quality of an aging oocyte as a major factor in the etiology of female infertility. Nevertheless, the cellular and molecular mechanisms responsible for the decreased oocyte quality with advanced maternal aging are not fully characterized. Herein we present information in the published literature and our own data to support the hypothesis that during aging induced decreases in mitochondrial ceramide levels and associated alterations in mitochondrial structure and function are prominent elements contributing to reduced oocyte quality. Hence, by examining the molecular determinants that underlie impairments in oocyte mitochondria, we expect to sieve to a better understanding of the mechanistic anatomy of oocyte aging.

Coenzyme Q10 supplement rescues postovulatory oocyte aging by regulating SIRT4 expression

2021 ◽  
Vol 14 ◽  
Author(s):  
Xupeng Xing ◽  
Jinjing Zhang ◽  
Jingcheng Zhang ◽  
Yongsheng Wang ◽  
Jingyi Wang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Mitochondrial Dysfunction ◽  
Coenzyme Q10 ◽  
Expression Patterns ◽  
Oocyte Quality ◽  
Developmental Competence ◽  
Ros Accumulation ◽  
Oocyte Aging ◽  
Modulation Of Gene Expression

Background: High-quality of the oocyte is crucial for embryo development and the success of human assisted reproduction. The postovulatory aged oocytes lose the developmental competence with mitochondrial dysfunction and oxidative stress. Coenzyme Q10 (CoQ10) is widely distributed in the membranes of cells, and has an important role in the mitochondrial respiration chain, against oxidative stress and modulation of gene expression. Objective: To investigate the functions and mechanisms of CoQ10 on delaying postovulatory oocyte aging. Methods: Quantitative real-time PCR and Immunofluorescence staining were used to determine the expression patterns of the biogenesis genes of CoQ10 in postovulatory aged oocytes compared with fresh oocytes. The mitochondrial function, apoptosis, reactive oxygen species (ROS) accumulation and spindle abnormalities were investigated after treatment with 10 μM CoQ10 in aged groups. SIRT4 siRNA or capped RNA was injected into oocytes to investigate the function of SIRT4 on postovulatory oocyte aging and the relationship between CoQ10 and SIRT4. Results: Multiple CoQ10 biosynthesis enzymes are insufficient, and supplement of CoQ10 can improve oocyte quality and elevate the development competency of postovulatory aged oocytes. CoQ10 can attenuate the aging-induced abnormalities including mitochondrial dysfunction, ROS accumulation, spindle abnormalities, and apoptosis in postovulatory aged oocytes. Furthermore, SIRT4, which was first found to be up-regulated in postovulatory aged oocytes, decreased following CoQ10 treatment. Finally, knockdown of SIRT4 can rescue aging-induced dysfunction of mitochondria, and the efficiency of CoQ10 rescuing dysfunction of mitochondria can be weakened by SIRT4 overexpression. Conclusion: Supplement of CoQ10 protects oocytes from postovulatory aging by inhibiting SIRT4increase.

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