Reactive oxygen species-scavenging nanomaterials for the prevention and treatment of age-related diseases.

With increasing proportion of the elderly in the population, age-related diseases (ARD) lead to a considerable healthcare burden to society. Prevention and treatment of ARD can decrease the negative impact of aging and the burden of disease. The aging rate is closely associated with the production of high levels of reactive oxygen species (ROS). ROS-mediated oxidative stress in aging triggers aging-related changes through lipid peroxidation, protein oxidation, and DNA oxidation. Antioxidants can control autoxidation by scavenging free radicals or inhibiting their formation, thereby reducing oxidative stress. Benefiting from significant advances in nanotechnology, a large number of nanomaterials with ROS-scavenging capabilities have been developed. ROS-scavenging nanomaterials can be divided into two categories: nanomaterials as carriers for delivering ROS-scavenging drugs, and nanomaterials themselves with ROS-scavenging activity. This study summarizes the current advances in ROS-scavenging nanomaterials for prevention and treatment of ARD, highlights the potential mechanisms of the nanomaterials used and discusses the challenges and prospects for their applications.

Towards prolonging ovarian reproductive life: Insights into trace elements homeostasis.

Ovarian aging is marked by a reduction in the quantity and quality of ovarian follicles, leading to a decline in female fertility and ovarian endocrine function. While the biological characteristics of ovarian aging are well-established, the exact mechanisms underlying this process remain elusive. Recent studies underscore the vital role of trace elements (TEs) in maintaining ovarian function. Imbalances in TEs can lead to ovarian aging, characterized by reduced enzyme activity, hormonal imbalances, ovulatory disorders, and decreased fertility. A comprehensive understanding of the relationship between systemic and cellular TEs balance and ovarian aging is critical for developing treatments to delay aging and manage age-related conditions. This review consolidates current insights into TEs homeostasis and its impact on ovarian aging, assesses how altered TEs metabolism affects ovarian aging, and suggests future research directions to prolong ovarian reproductive life. These studies are expected to offer novel approaches for mitigating ovarian aging.

Spatiotemporal transcriptomic changes of human ovarian aging and the regulatory role of FOXP1.

Limited understanding exists regarding how aging impacts the cellular and molecular aspects of the human ovary. This study combines single-cell RNA sequencing and spatial transcriptomics to systematically characterize human ovarian aging. Spatiotemporal molecular signatures of the eight types of ovarian cells during aging are observed. An analysis of age-associated changes in gene expression reveals that DNA damage response may be a key biological pathway in oocyte aging. Three granulosa cells subtypes and five theca and stromal cells subtypes, as well as their spatiotemporal transcriptomics changes during aging, are identified. FOXP1 emerges as a regulator of ovarian aging, declining with age and inhibiting CDKN1A transcription. Silencing FOXP1 results in premature ovarian insufficiency in mice. These findings offer a comprehensive understanding of spatiotemporal variability in human ovarian aging, aiding the prioritization of potential diagnostic biomarkers and therapeutic strategies.

Multiomics insights into the female reproductive aging.

The human female reproductive lifespan significantly diminishes with age, leading to decreased fertility, reduced fertility quality and endocrine function disorders. While many aspects of aging in general have been extensively documented, the precise mechanisms governing programmed aging in the female reproductive system remain elusive. Recent advancements in omics technologies and computational capabilities have facilitated the emergence of multiomics deep phenotyping. Through the application and refinement of various high-throughput omics methods, a substantial volume of omics data has been generated, deepening our comprehension of the pathogenesis and molecular underpinnings of reproductive aging. This review highlights current and emerging multiomics approaches for investigating female reproductive aging, encompassing genomics, epigenomics, transcriptomics, proteomics, metabolomics, and microbiomics. We elucidate their influence on fundamental cell biology and translational research in the context of reproductive aging, address the limitations and current challenges associated with multiomics studies, and offer a glimpse into future prospects.

Inhibition of checkpoint kinase prevents human oocyte apoptosis induced by chemotherapy and allows enhanced tumour chemotherapeutic efficacy.

STUDY QUESTION: Could inhibition of the checkpoint kinase (CHEK) pathway protect human oocytes and even enhance the anti-tumour effects, during chemotherapy? SUMMARY ANSWER: CHEK inhibitors prevented apoptosis of human oocytes induced by chemotherapy and even enhanced the anti-tumour effects. WHAT IS KNOWN ALREADY: CHEK inhibitors showed ovarian protective effects in mice during chemotherapy, while their role in human oocytes is unclear. STUDY DESIGN, SIZE, DURATION: This experimental study evaluated the ovarian reserve of young patients (120 patients) with cancer, exposed or not exposed to taxane and platinum (TP)-combined chemotherapy. Single RNA-sequencing analysis of human primordial oocytes from 10 patients was performed to explore the mechanism of oocyte apoptosis induced by TP chemotherapy. The damaging effects of paclitaxel (PTX) and cisplatin on human oocytes were also evaluated by culturing human ovaries in vitro. A new mouse model that combines human ovarian xenotransplantation and patient-derived tumour xenografts was developed to explore adjuvant therapies for ovarian protection. The mice were randomly allocated to four groups (10 mice for each group): control, cisplatin, cisplatin + CK1 (CHEK1 inhibitor, SCH 900776), and cisplatin + CK2 (CHEK2 inhibitor, BML277). PARTICIPANTS/MATERIALS, SETTING, METHODS: In the prospective cohort study, human ovarian follicles were counted and serum AMH levels were evaluated. RNA-sequencing analysis was conducted, and staining for follicular damage (phosphorylated H2AX histone; γH2AX), terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labelling (TUNEL) assays and assessments of apoptotic biomarkers (western blot and immunofluorescence) were conducted in human ovaries. After the treatments, histological analysis was performed on human ovarian samples to investigate follicular populations, and oocyte damage was measured by γH2AX staining, BAX staining, and TUNEL assays. At the same time, the tumours were evaluated for volume, weight, and apoptosis levels. MAIN RESULTS AND THE ROLE OF CHANCE: Patients who received TP chemotherapy showed decreased ovarian reserves. Single RNA-sequencing analysis of human primordial oocytes indicated that TP chemotherapy induced apoptosis of human primordial oocytes by causing CHEK-mediated TAp63α phosphorylation. In vitro culture of human ovaries showed greater damaging effects on oocytes after cisplatin treatment compared with that after PTX treatment. Using the new animal model, CHEK1/2 inhibitors prevented the apoptosis of human oocytes induced by cisplatin and even enhanced its anti-tumour effects. This protective effect appeared to be mediated by inhibiting DNA damage via the CHEK-TAp63α pathway and by generation of anti-apoptotic signals in the oocytes. LARGE SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: This was a preclinical study performed with human ovarian samples, and clinical research is required for validation. WIDER IMPLICATIONS OF THE FINDINGS: These findings highlight the therapeutic potential of CHEK1/2 inhibitors as a complementary strategy for preserving fertility in female cancer patients. STUDY FUNDING/COMPETING INTEREST(S): This work was financially supported by the National Natural Science Foundation of China (nos. 82001514 and 81902669) and the Fundamental Research Funds for the Central Universities (2021yjsCXCY087). The authors declare no conflict of interest.

Ovarian reserve in reproductive-aged patients with cancer before gonadotoxic treatment: a systematic review and meta-analysis.

STUDY QUESTION: Does cancer itself, before any gonadotoxic treatment, affect ovarian function in reproductive-aged patients? SUMMARY ANSWER: Our study revealed that women with cancer may have decreased ovarian reserve markers even before cancer therapy. WHAT IS KNOWN ALREADY: With the field 'oncofertility' improving rapidly, cancer therapy-mediated ovarian damage is well characterized. However, there is a controversy about whether cancer itself affects ovarian function before gonadotoxic treatment. STUDY DESIGN SIZE DURATION: We conducted a systematic meta-analysis investigating the association between cancer and ovarian function prior to gonadotoxic treatment. Titles or abstracts related to ovarian reserve (e.g. anti-Müllerian hormone (AMH), antral follicle count (AFC), or basal follicle-stimulating hormone (FSH)) combined with titles or abstracts related to the exposure (e.g. cancer*, oncolog*, or malignan*) were searched in PubMed, Embase, and Web of Science databases from inception to 1 February 2022. PARTICIPANTS/MATERIALS SETTING METHODS: We included cohort, case-control, and cross-sectional studies in English that examined ovarian reserve in reproductive-aged patients (18-45 years) with cancer compared to age-matched controls before cancer treatment. The quality of the included studies was assessed by ROBINS-I. Fixed or random effects were conducted to estimate standard or weighted mean difference (SMD or WMD, respectively) and CI. Heterogeneity was assessed by the Q test and I2 statistics, and publication bias was evaluated by Egger's and Begg's tests. MAIN RESULTS AND THE ROLE OF CHANCE: The review identified 17 eligible studies for inclusion. The results showed that cancer patients had lower serum AMH levels compared to healthy controls (SMD = -0.19, 95% CI = -0.34 to -0.03, P = 0.001), especially women with hematological malignancies (SMD = -0.62, 95% CI = -0.99 to -0.24, P = 0.001). The AFC was also decreased in patients with cancer (WMD = -0.93, 95% CI = -1.79 to -0.07, P = 0.033) compared to controls, while inhibin B and basal FSH levels showed no statistically significant differences. LIMITATIONS REASONS FOR CAUTION: Serum AMH and basal FSH levels in this meta-analysis showed high heterogeneity, and the small number of studies contributing to most subgroup analyses limited the heterogeneity analysis. Moreover, the studies for specific cancer subtypes may be too small to draw conclusions; more studies are needed to investigate the possible impact of cancer type and stage on ovarian function. WIDER IMPLICATIONS OF THE FINDINGS: Our study confirmed the findings that cancer per se, especially hematological malignancies, negatively affects serum AMH level, and AFC values of reproductive-aged women. However, the lower AMH levels and AFC values may also be due to the changes in ovarian physiology under oncological conditions, rather than actual lower ovarian reserves. Based on the meta-analysis, clinicians should raise awareness about the possible need for personalized approaches for young women with cancer who are interested in pursuing fertility preservation strategies before anticancer treatments. STUDY FUNDING/COMPETING INTERESTS: This work was financially supported by the National Natural Science Foundation of China (nos 81873824, 82001514, and 81902669) and the Applied Basic Research Program of Wuhan Municipal Bureau of Science and Technology (2019020701011436). The authors declare that they have no conflicts of interest. REGISTRATION NUMBER: PROSPERO (CRD42021235954).

Local excision as a viable alternative to hysterectomy for early-stage cervical cancer in women of reproductive age: a population-based cohort study.

BACKGROUND: Local excision as the main alternative for fertility-sparing surgery (FSS) has been widely used in patients with early-stage cervical cancer to achieve fertility preservation, but its safety and practicability are still questioned. Therefore, The authors evaluated the current application of local excision in early-stage cervical cancer with this population-based study and compared its efficacy with hysterectomy. MATERIALS AND METHODS: Women diagnosed with International Federation of Gynecology and Obstetrics (FIGO) stage I cervical cancer at childbearing age (18-49 years) recorded in the Surveillance, Epidemiology and End Results (SEER) database from 2000 to 2017 were included. Overall survival (OS) and disease-specific survival (DSS) rates were compared between local excision and hysterectomy. RESULTS: A total of 18 519 patients of reproductive age with cervical cancer were included, and 2268 deaths were observed. 17.0% of patients underwent FSS via local excision, and 70.1% underwent hysterectomy. Among patients younger than 39 years, OS and DSS of local excision were comparable to those of hysterectomy, whereas, in patients older than 40 years, OS and DSS of local excision were significantly worse than those of hysterectomy. In addition, OS and DSS of local excision were similar to hysterectomy in patients with stage IA cervical cancer, but OS and DSS were inferior to hysterectomy in patients with stage IB cervical cancer who underwent local excision. CONCLUSION: For patients without fertility requirements, hysterectomy remains the best therapeutic option. However, for patients under 40 years of age diagnosed with stage IA cervical cancer, FSS via local excision is a viable option that can achieve a well-balanced outcome between tumour control and fertility preservation.

MiR-145 regulates steroidogenesis in mouse primary granulosa cells by targeting Arpc5 and subsequent cytoskeleton remodeling.

MicroRNA (miR)-145 is enriched in the follicular granulosa cells (GCs) of 3-week-old mice. Downregulating miR-145 inhibits the proliferation and differentiation of GCs and induces evident changes in their cytoskeleton. In this study, we examined how miR-145 induces cytoskeletal changes in mouse GCs and its potential mechanism in regulating GC steroidogenesis. We found that actin related protein 2/3 complex subunit 5 (Arpc5) is a target of miR-145. The miR-145 antagomir increased ARPC5 expression but not ß-ACTIN, ß-TUBULIN, and PAXILLIN expression. Arpc5 overexpression inhibited GC proliferation, differentiation, and progesterone synthesis. Furthermore, the expression of progesterone synthesis-associated enzymes was downregulated in the Arpc5 overexpression group, and the GC cytoskeleton exhibited evident changes. We conclude that Arpc5, a new target of miR-145, regulates primary GC proliferation and progesterone production by regulating the cytoskeleton remodeling.

Abiotic Synthetic Antibody Inhibitor with Broad-Spectrum Neutralization and Antiviral Efficacy against Escaping SARS-CoV-2 Variants.

The rapid emergence and spread of vaccine/antibody-escaping variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has posed serious challenges to our efforts in combating corona virus disease 2019 (COVID-19) pandemic. A potent and broad-spectrum neutralizing reagent against these escaping mutants is extremely important for the development of strategies for the prevention and treatment of SARS-CoV-2 infection. We herein report an abiotic synthetic antibody inhibitor as a potential anti-SARS-CoV-2 therapeutic agent. The inhibitor, Aphe-NP14, was selected from a synthetic hydrogel polymer nanoparticle library created by incorporating monomers with functionalities complementary to key residues of the SARS-CoV-2 spike glycoprotein receptor binding domain (RBD) involved in human angiotensin-converting enzyme 2 (ACE2) binding. It has high capacity, fast adsorption kinetics, strong affinity, and broad specificity in biologically relevant conditions to both the wild type and the current variants of concern, including Beta, Delta, and Omicron spike RBD. The Aphe-NP14 uptake of spike RBD results in strong blockage of spike RBD-ACE2 interaction and thus potent neutralization efficacy against these escaping spike protein variant pseudotyped viruses. It also inhibits live SARS-CoV-2 virus recognition, entry, replication, and infection in vitro and in vivo. The Aphe-NP14 intranasal administration is found to be safe due to its low in vitro and in vivo toxicity. These results establish a potential application of abiotic synthetic antibody inhibitors in the prevention and treatment of the infection of emerging or possibly future SARS-CoV-2 variants.

Study on Ag(I) Loaded ZIF-8 and Ag(I) Ion Release in Artificial Seawater.

From a porous structure perspective, the one-stage de novo synthesis method and impregnation method were applied to synthesize Ag(I) ion-containing ZIF-8 samples. With the de novo synthesis method, Ag(I) ions could be located inside micropores or adsorbed on the external surface of the ZIF-8 by selecting AgNO3 in water or Ag2CO3 in ammonia solution as precursors, respectively. The ZIF-8 confining Ag(I) ion exhibited a much lower constant releasing rate than the Ag(I) ion adsorbed on the ZIF-8 surface in artificial seawater. As such, strong diffusion resistance in association with the confinement effect is contributed by ZIF-8's micropore. On the other hand, the release of Ag(I) ions adsorbed on the external surface was diffusion limited. Therefore, the releasing rate would reach a maximum not increasing with Ag(I) loading in the ZIF-8 sample.

Semaphorin 4C regulates ovarian steroidogenesis through RHOA/ROCK1-mediated actin cytoskeleton rearrangement.

Semaphorins are a family of evolutionarily conserved morphogenetic molecules that were initially found to be associated with axonal guidance. Semaphorin 4C (Sema4C), a member of the fourth subfamily of semaphorins, has been demonstrated to play multifaceted and important roles in organ development, immune regulation, tumor growth, and metastasis. However, it is completely unknown whether Sema4C is involved in the regulation of ovarian function. We found that Sema4C was widely expressed in the stroma, follicles, and corpus luteum of mouse ovaries, and its expression was decreased at distinct foci in ovaries of mice of mid-to-advanced reproductive age. Inhibition of Sema4C by the ovarian intrabursal administration of recombinant adeno-associated virus-shRNA significantly reduced oestradiol, progesterone, and testosterone levels in vivo. Transcriptome sequencing analysis showed changes in pathways related to ovarian steroidogenesis and the actin cytoskeleton. Similarly, knockdown of Sema4C by siRNA interference in mouse primary ovarian granulosa cells or thecal interstitial cells significantly suppressed ovarian steroidogenesis and led to actin cytoskeleton disorganization. Importantly, the cytoskeleton-related pathway RHOA/ROCK1 was simultaneously inhibited after the downregulation of Sema4C. Furthermore, treatment with a ROCK1 agonist after siRNA interference stabilized the actin cytoskeleton and reversed the inhibitory effect on steroid hormones described above. In conclusion, Sema4C may play an important role in ovarian steroidogenesis through regulation of the actin cytoskeleton via the RHOA/ROCK1 signaling pathway. These findings shed new light on the identification of dominant factors involved in the endocrine physiology of female reproduction.

The effects and mechanism of taxanes on chemotherapy-associated ovarian damage: A review of current evidence.

Chemotherapy is often a cause of premature ovarian insufficiency and infertility since the ovarian follicles are extremely sensitive to the effects of chemotherapeutic agents. Different chemotherapeutic agents with varying mechanisms of action may damage ovarian function differently. Taxanes are widely used in clinical cancer treatment, but the specific reproductive toxicological information is still controversial. This review described the impact and duration of taxanes on ovarian function in women and analyzed the possible reasons for different conclusions. Furthermore, the toxicity of taxanes on ovarian function and its possible mechanisms were discussed. The potential protective strategies and agents against ovarian damage induced by taxanes are also reviewed.

Biomaterials and advanced technologies for the evaluation and treatment of ovarian aging.

Ovarian aging is characterized by a progressive decline in ovarian function. With the increase in life expectancy worldwide, ovarian aging has gradually become a key health problem among women. Over the years, various strategies have been developed to preserve fertility in women, while there are currently no clinical treatments to delay ovarian aging. Recently, advances in biomaterials and technologies, such as three-dimensional (3D) printing and microfluidics for the encapsulation of follicles and nanoparticles as delivery systems for drugs, have shown potential to be translational strategies for ovarian aging. This review introduces the research progress on the mechanisms underlying ovarian aging, and summarizes the current state of biomaterials in the evaluation and treatment of ovarian aging, including safety, potential applications, future directions and difficulties in translation.

Carbon tetrachloride exposure induces ovarian damage through oxidative stress and inflammatory mediated ovarian fibrosis.

Carbon tetrachloride (CCL4) is widely used as a chemical intermediate and as a feedstock in the production of chlorofluorocarbons. CCL4 is highly toxic in the liver, kidney, testicle, brain and other tissues. However, the effect of CCL4 on ovarian function has not been reported. In this study, we found that the mice treated with CCL4 showed decreased ovarian function with disturbed estrus cycle, decreased serum level of 17ß-estradiol and the reduced number of healthy follicles. Ovarian damage was accompanied by oxidative stress and the production of proinflammatory cytokines, especially interleukins. The indicators of oxidative stress, 4-Hydroxynonenal (4-HNE), 8-hydroxy-2´-deoxyguanosine (8-OHdG), 3-Nitrotyrosine (3-NT) and malondialdehyde (MDA), and the levels of proinflammatory cytokines IL-1α, IL-1ß, IL-6 and IL-11 were increased, while the antioxidants, including superoxide dismutase (SOD), nuclear factor erythroid2-related factor 2 (NRF2) and heme oxygenase-1 (HO-1), were decreased in the CCL4 group. In the CCL4 treated group, the results of Sirius Red staining, immunohistochemistry and qPCR indicated that proinflammatory cytokines caused further ovarian fibrosis. And CCL4 could also promote ovarian thecal cells to secrete inflammatory cytokines, resulting in fibrosis in vitro. In addition, CCL4 inhibited oocyte development and triggered oocyte apoptosis. In conclusion, CCL4 exposure causes ovarian damage by strong oxidative stress and the high expression of the proinflammatory cytokine mediated ovarian fibrosis.

Chronic exposure to propylparaben at the humanly relevant dose triggers ovarian aging in adult mice.

Parabens, a type of endocrine-disrupting chemicals, are widely used as antibacterial preservatives in food and cosmetics in daily life. Paraben exposure has gained particular attention in the past decades, owing to its harmful effects on reproductive function. Whether low-dose paraben exposure may cause ovarian damage has been ignored recently. Here, we investigated the effects of chronic low-dose propylparaben (PrPB) exposure on ovarian function. Female C57BL/6J mice were exposed to PrPB at a humanly relevant dose for 8 months. Our results showed that chronic exposure to PrPB at a humanly relevant dose significantly altered the estrus cycle, hormone levels, and ovarian reserve, accelerating ovarian aging in adult mice. These effects are accompanied by oxidative stress enrichment, leading to steroidogenesis dysfunction and acceleration of primordial follicle recruitment. Notably, melatonin supplementation has been shown to protect against PrPB-induced steroidogenesis dysfunction in granulosa cells. Here, we report that daily chronic PrPB exposure may contribute to ovarian aging by altering oxidative stress-mediated JNK and PI3K-AKT signaling regulation, and that melatonin may serve as a pharmaceutical candidate for PrPB-associated ovarian dysfunction.

MiR-145 regulates steroidogenesis in mouse primary granulosa cells through targeting Crkl.

AIMS: It has been demonstrated that miR-145 is expressed in primordial follicles and modulates the initiation of primordial follicle development. We aimed to explore the function of miR-145 in mouse granulosa cells (mGCs). MATERIALS AND METHODS: The proliferation and differentiation of GCs were examined via MTT, EDU assay, QRT-PCR, ELISA and electron microscope analysis. The target of miR-145 was determined by bioinformatics analysis and luciferase reporter assay and the molecular mechanisms were examined via western blot and quantitative Real-Time RT-PCR. KEY FINDINGS: We proved that down-regulation of miR-145 could inhibit GCs proliferation and differentiation. In addition, we provided evidence that Crkl was the target gene of miR-145. The miR-145 antagomir caused an increase in Crkl expression and activation of the JNK/p38 MAPK pathway. Overexpression of Crkl with pEGFP-N1-Crkl vector inhibited GCs differentiation and progesterone synthesis as well as activation of the JNK/p38 MAPK pathway. SIGNIFICANCE: Our study shows that miR-145 targets Crkl and through the JNK/p38 MAPK signaling pathway promotes the GCs proliferation, differentiation, and steroidogenesis. MiR-145 may play an important role in the ovarian physiology and pathology.

THERAPY OF ENDOCRINE DISEASE: Novel protection and treatment strategies for chemotherapy-associated ovarian damage.

Fertility and ovarian protection against chemotherapy-associated ovarian damage has formed a new field called oncofertility, which is driven by the pursuit of fertility protection as well as good life quality for numerous female cancer survivors. However, the choice of fertility and ovarian protection method is a difficult problem during chemotherapy and there is no uniform guideline at present. To alleviate ovarian toxicity caused by anticancer drugs, effective methods combined with an individualized treatment plan that integrates an optimal strategy for preserving and restoring reproductive function should be offered from well-established to experimental stages before, during, and after chemotherapy. Although embryo, oocyte, and ovarian tissue cryopreservation are the major methods that have been proven effective and feasible for fertility protection, they are also subject to many limitations. Therefore, this paper mainly discusses the future potential methods and corresponding mechanisms for fertility protection in chemotherapy-associated ovarian damage.

Resveratrol alleviates chemotherapy-induced oogonial stem cell apoptosis and ovarian aging in mice.

Chemotherapy-induced ovarian aging not only increases the risk for early menopause-related complications but also results in infertility in young female cancer survivors. Oogonial stem cells have the ability to generate new oocytes and thus provide new opportunities for treating ovarian aging and female infertility. Resveratrol (3,5,4'-trihydroxy-trans-stilbene) is a natural phenol derived from plants, that has been shown to have positive effects on longevity and redox flow in lipid metabolism and a preventive function against certain tumors. To evaluate whether resveratrol could promote the repair of oogonial stem cells damage in a busulfan/cyclophosphamide (Bu/Cy)-induced accelerated ovarian aging model, female mice were administered 30 and 100 mg/kg/d resveratrol through a gavage for 2 weeks. We demonstrated that resveratrol (30 mg/kg/d) relieved oogonial stem cells loss and showed an attenuating effect on Bu/Cy-induced oxidative apoptosis in mouse ovaries, which may be attributed to the attenuation of oxidative levels in ovaries. Additionally, we also showed that Res exerted a dose-dependent effect on oogonial stem cells and attenuated H2O2-induced cytotoxicity and oxidative stress injury by activating Nrf2 in vitro. Therefore, resveratrol could be of a potential therapeutic drug used to prevent chemotherapy-induced ovarian aging.