STUDY QUESTION: What is the current burden of infertility attributable to PCOS at global, regional, and national levels by age and socio-demographic index (SDI) across 21 regions and 204 countries and territories? SUMMARY ANSWER: The burden of infertility attributable to PCOS increased from 6.00 million prevalent cases in 1990 to 12.13 million in 2019 globally and increased sharply in most regions and nations. WHAT IS KNOWN ALREADY: PCOS is the most common cause of anovulatory infertility, affecting up to 80% of women with anovulation. No comprehensive and detailed epidemiological estimates of infertility attributable to PCOS in reproductive women aged 15–49 years by age and SDI, at the global, regional, and national level, have been reported. STUDY DESIGN, SIZE, DURATION: An age- and SDI-stratified systematic analysis of the prevalence and years lived with disability (YLD) of infertility attributable to PCOS across 21 regions and 204 countries and territories from 1990 to 2019 has been performed. PARTICIPANTS/MATERIALS, SETTING, METHODS: The prevalence and YLD of female infertility attributable to PCOS in reproductive women aged 15–49 years from 1990 to 2019 were retrieved directly from the Global Burden of Diseases 2019. The number, rates per 100 000 persons, and average annual percentage changes (AAPCs) of prevalence and YLD were estimated at the global, regional, and national levels. MAIN RESULTS AND THE ROLE OF CHANCE: Globally, the prevalent cases of infertility attributable to PCOS among women of reproductive age (15–49 years) doubled from 1990 to 2019, with 6.00 million prevalent cases in 1900 and 12.13 million in 2019. The global age-standardized prevalence rates (ASPRs) of infertility attributable to PCOS were 223.50/100 000 persons in 1990 and 308.25/100 000 persons in 2019. At global level, the YLDs of infertility attributable to PCOS increased by 98.0% from 35.20 thousand in 1990 to 69.70 thousand in 2019. The burden of infertility attributable to PCOS in the high SDI region was significantly higher than that in the other four SDI regions. The greatest annual increases in rates of ASPR and age-standardized YLD rate were observed in the middle SDI region (AAPC 1.96 [95% CI 1.87–2.06], 1.94 [1.87–2.00], respectively) and the low-middle SDI region (AAPC 1.96 [1.90–2.03], 1.90 [1.85–1.94], respectively). The regional highest ASPR and the age-standardized YLD rate of infertility were observed in High-income Asia Pacific. The national highest ASPR and the age-standardized YLD rate of infertility were observed in Italy. Positive associations were observed between these burden estimates and the SDI level (all P < 0.001). LIMITATIONS, REASONS FOR CAUTION: Although the Global Burden of Diseases 2019 has tried its best to collect all available data, some countries have limited data, which may result in an underestimation of the burden of infertility attributable to PCOS. The diagnostic criteria of PCOS are constantly changing, which may induce bias in infertility attributable to PCOS. No information on the PCOS phenotype is provided in the Global Burden of Diseases 2019, so we cannot estimate the infertility attributable to a specific PCOS phenotype. Detection bias would lead to a higher prevalence of PCOS and infertility attributable to PCOS in developed countries with well-established medical systems and greater willingness of the populace to seek medical attention. Thus, health resource allocation for infertility attributable to PCOS in low-prevalence areas should not be ignored. WIDER IMPLICATIONS OF THE FINDINGS: The global burden of infertility attributable to PCOS increased sharply from 1990 to 2019. Effective health interventions and efficient preventative and managerial strategies should be established to reduce the burden of infertility attributable to PCOS. Weight control is suggested to reduce the burden of infertility attributable to PCOS, especially in the high SDI region. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by the National Key Research and Development Program of China (grant number, 2022YFC2704100) and the National Natural Science Foundation of China (Nos 82001498 and 82371648). The authors declare no competing interests. TRIAL REGISTRATION NUMBER: N/A

The aim of this study was to design and fabricate a three-dimensional (3D) printed artificial ovary.We first compared the printability of gelatin-methacryloyl (GelMA), alginate and GelMA–alginate b... 目的：本研究的目的是设计和制造一个3D打印的人工卵巢。方法：我们首先比较了明胶-甲基丙烯酰基 (GelMA)、藻酸盐和 GelMA-藻酸盐生物墨水的可印刷性, 并选取GelMA 进行进一步研究。 GelMA支架的溶胀和降解性能、形状保真度通过溶胀/冻干平衡、胶原酶降解和微型计算机断层扫描评估来表征。利用商业化的卵巢肿瘤细胞系（COV434、KGN、ID8）和原代培养卵巢体细胞进行载细胞3D打...

Uterine aging is an important factor that impacts fertility, reproductive health, and uterus-related diseases; however, it remains poorly explored. Functionally, these disturbances have been associated with an abnormal hormonal response in the endometrium and decreased endometrial receptivity. Based on emerging evidence, these alterations are mediated via the senescence of endometrial stem cells and impaired decidualization of endometrial stromal cells. Multiple molecular activities may participate in uterine aging, including oxidative stress, inflammation, fibrosis, DNA damage response, and cellular senescence. Over the past decade, several protective strategies targeting these biological processes have afforded promising results, including stem cell therapy, anti-aging drugs, and herbal medicines. However, the currently available evidence is fragmented and scattered. Here, we summarize the most recent findings regarding uterine aging, including functional and structural alterations and potential cellular and molecular mechanisms, and discuss potential protective interventions against uterine aging. Thereby, we hope to provide a comprehensive understanding of the pathophysiological processes and underlying mechanisms associated with uterine aging, as well as improve fecundity and reproductive outcomes in females of advanced reproductive age.

Ovarian injury caused by chemotherapy can lead to early menopause, infertility, and even premature senility in female cancer patients, impairing the quality of life and overall health of the cancer survivors seriously. However, there is still a lack of effective protection strategies against such injury. Cellular senescence can be induced by chemotherapeutic agents in multiple organs and may corrode the structure and function of normal tissues. We hypothesized that the widely used first-line chemotherapy drug, doxorubicin, could increase senescent cell burden in normal ovarian tissue during the therapeutic process and that elimination of senescent cells with senolytics would ameliorate doxorubicin-induced ovarian injury. Here, we demonstrated an accumulation of cellular senescence in doxorubicin-treated ovaries through detecting p16 and p21 expression levels and senescence-associated β-galactosidase (SA-β-gal) activity as well as senescence-associated secretory phenotype (SASP) factors. Short-term intervention with the classic senolytic combination dasatinib and quercetin (DQ) or fisetin significantly reduced the load of senescent cells in ovaries after doxorubicin treatment. However, neither DQ nor fisetin alleviated doxorubicin-related ovarian dysfunction. Further experiments showed that ovarian apoptosis and fibrosis following doxorubicin exposure could not be improved by senolytics. Collectively, our study shows that senolytic treatment can eliminate accumulated senescent cells, but cannot reverse the massive follicle loss and ovarian stromal fibrosis caused by doxorubicin, suggesting that cellular senescence may not be one of the key mechanisms in doxorubicin-induced ovarian injury.

Ovarian damage induced by platinum‐based chemotherapy seriously affects young women with cancer, manifesting as infertility, early menopause, and premature ovarian insufficiency. However, effective prevention strategies for such damage are lacking. Senescent cells may be induced by chemotherapeutic agents. We hypothesized that cisplatin can lead to senescence in ovarian cells during the therapeutic process, and senolytic drugs can protect animals against cisplatin‐induced ovarian injury. Here, we demonstrated the existence of senescent cells in cisplatin‐treated ovaries, identified the senescence‐associated secretory phenotype, and observed significant improvement of ovarian function by treatment with metformin or dasatinib and quercetin (DQ) independently or in combination. These senotherapies improved both oocyte quality and fertility, increased the ovarian reserve, and enhanced hormone secretion in cisplatin‐exposed mice. Additionally, attenuated fibrosis, reorganized subcellular structure, and mitigated DNA damage were observed in the ovaries of senotherapeutic mice. Moreover, RNA sequencing analysis revealed upregulation of the proliferation‐related genes Ki, Prrx2, Sfrp4, and Megfl0; and the antioxidative gene H2-Q10 after metformin plus DQ treatment. Gene ontology analysis further revealed that combining senotherapies enhanced ovarian cell differentiation, development, and communication. In this study, we demonstrated that metformin plus DQ recovered ovarian function to a greater extent compared to metformin or DQ independently, with more follicular reserve, increased pups per litter, and reduced DNA damage. Collectively, our work indicates that senotherapies might prevent cisplatin‐induced ovarian injury by removing senescent cells and reducing DNA damage, which represent a promising therapeutic avenue to prevent chemotherapy‐induced ovarian damage.