Spatiotemporal Dynamics of Human Ovarian Cortex Transcriptome Following Vitrification and Thawing: Insights into the FOS/AP-1 Pathway DOI
Wen Li,

Fanghao Guo,

Di Sun

et al.

Research Square (Research Square), Journal Year: 2025, Volume and Issue: unknown

Published: April 4, 2025

Abstract Ovary is a vital and dynamic reproductive organ. Ovarian tissue cryopreservation (OTC) plays role in female fertility preservation, especially for adolescent cancer patients. Yet, the sensitive cell populations cryoinjury molecular mechanisms underlying remain elusive. This study employs single-cell RNA sequencing spatial transcriptomics to dissect impacts of temperature stress cryoprotectant toxicity on human ovarian cortex. The spatiotemporal characteristics eight types following vitrification-thawing had been comprehensively characterized. Granulosa, perivascular stromal cells are identified as most OTC procedure. Further analysis using Smart-seq2 oocytes highlights alterations in“cell cycle” “DNA methylation” pathways. Notably, FOS/AP-1 pathway emerges crucial response factor during cryopreservation. Inhibition this with T-5224 mitigates vascular damage reduces apoptosis vitrification-thawed ovaries. These findings provide insight into dynamics vitrification thawing, aiding prioritizing therapeutic strategies pre- post-cryopreservation interventions.

Language: Английский

Spatiotemporal transcriptomic changes of human ovarian aging and the regulatory role of FOXP1 DOI Creative Commons
Meng Wu, Weicheng Tang, Runsheng Chen

et al.

Nature Aging, Journal Year: 2024, Volume and Issue: 4(4), P. 527 - 545

Published: April 9, 2024

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

Language: Английский

Citations

32
Ovarian microenvironment: challenges and opportunities in protecting against chemotherapy-associated ovarian damage DOI Creative Commons

Yican Guo,

Liru Xue,

Weicheng Tang

et al.

Human Reproduction Update, Journal Year: 2024, Volume and Issue: 30(5), P. 614 - 647

Published: June 28, 2024

Chemotherapy-associated ovarian damage (CAOD) is one of the most feared short- and long-term side effects anticancer treatment in premenopausal women. Accumulating detailed data show that different chemotherapy regimens can lead to disturbance hormone levels, reduced or lost fertility, an increased risk early menopause. Previous studies have often focused on direct chemotherapeutic drugs follicles, such as DNA damage-mediated apoptotic death primordial follicle burnout. Emerging evidence has revealed imbalance microenvironment during chemotherapy. The provides nutritional support transportation signals stimulate growth development ovulation, corpus luteum formation. close interaction between follicles determine function. Therefore, designing novel precise strategies manipulate may be a new strategy protect function

Language: Английский

Citations

14
Aging atlas reveals cell-type-specific effects of pro-longevity strategies DOI Creative Commons
Shihong Max Gao, Yanyan Qi, Qinghao Zhang

et al.

Nature Aging, Journal Year: 2024, Volume and Issue: 4(7), P. 998 - 1013

Published: May 30, 2024

Abstract Organismal aging involves functional declines in both somatic and reproductive tissues. Multiple strategies have been discovered to extend lifespan across species. However, how age-related molecular changes differ among various tissues those lifespan-extending slow tissue distinct manners remain unclear. Here we generated the transcriptomic Cell Atlas of Worm Aging (CAWA, http://mengwanglab.org/atlas ) wild-type long-lived strains. We cell-specific, signatures all germ cell types. developed clocks for different quantitatively determined three pro-longevity distinctively. Furthermore, through genome-wide profiling alternative polyadenylation (APA) events tissues, cell-type-specific APA during revealed these are differentially affected by strategies. Together, this study offers fundamental insights into provides a valuable resource in-depth understanding diversity mechanisms.

Language: Английский

Citations

13
The role of cellular senescence in ovarian aging DOI Creative Commons
Jéssica D. Hense, José V.V. Isola, Driele N. Garcia

et al.

npj Aging, Journal Year: 2024, Volume and Issue: 10(1)

Published: July 20, 2024

Abstract This review explores the relationship between ovarian aging and senescent cell accumulation, as well efficacy of senolytics to improve reproductive longevity. Reproductive longevity is determined by age-associated decline in reserve, resulting reduced fertility eventually menopause. Cellular senescence a state permanent cycle arrest resistance apoptosis. Senescent cells accumulate several tissues with advancing age, thereby promoting chronic inflammation age-related diseases. Ovaries also appear which might contribute system whole organism through SASP production. Importantly, senolytic drugs can eliminate may present potential intervention mitigate aging. Herein, we current literature related for extending window mice.

Language: Английский

Citations

8
Reproductive Ageing: Inflammation, immune cells, and cellular senescence in the aging ovary DOI Creative Commons

José V. V. Isola,

Jéssica D. Hense,

César A P Osório

et al.

Reproduction, Journal Year: 2024, Volume and Issue: 168(2)

Published: May 13, 2024

In brief Recent reports suggest a relationship between ovarian inflammation and functional declines, although it remains unresolved if is the cause or consequence of aging. this review, we compile available literature in area point to several current knowledge gaps that should be addressed through future studies. Abstract Ovarian aging results reduced fertility, disrupted endocrine signaling, an increased burden chronic diseases. The factors contributing natural decline follicles throughout reproductive life are not fully understood. Nevertheless, local may play important role driving Inflammation progressively rises aged ovaries during window, potentially affecting fertility. addition inflammatory markers, recent studies show accumulation specific immune cell populations ovaries, particularly lymphocytes. Other hallmarks ovary include formation multinucleated giant cells, collagen deposition, markers cellular senescence. Collectively, these changes significantly impact quantity quality oocytes. This review explores on alterations associated with inflammation, fibrosis, senescence, cells ovary.

Language: Английский

Citations

7
Molecular and genetic insights into human ovarian aging from single-nuclei multi-omics analyses DOI Creative Commons
Chen Jin,

Xizhe Wang,

Jiping Yang

et al.

Nature Aging, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 22, 2024

The ovary is the first organ to age in human body, affecting both fertility and overall health. However, biological mechanisms underlying ovarian aging remain poorly understood. Here we present a comprehensive single-nuclei multi-omics atlas of four young (ages 23–29 years) reproductively aged 49–54 ovaries. Our analyses reveal coordinated changes transcriptomes chromatin accessibilities across cell types during aging, notably mTOR signaling being prominent ovary-specific pathway. Cell-type-specific regulatory networks enhanced activity transcription factor CEBPD ovary. Integration our data with genetic variants associated at natural menopause demonstrates global impact functional on gene types. We nominate non-coding variants, their target genes mechanisms. This provides valuable resource for understanding cellular, molecular basis aging. cellular are incompletely authors provide RNA ATAC-seq tissue from donors, revealing transcriptomic epigenomic highlighting role reproductive

Language: Английский

Citations

7
Shear wave elastography to assess stiffness of the human ovary and other reproductive tissues across the reproductive lifespan in health and disease DOI Creative Commons
Emily J. Zaniker, Man Zhang, Lydia Hughes

et al.

Biology of Reproduction, Journal Year: 2024, Volume and Issue: 110(6), P. 1100 - 1114

Published: April 11, 2024

Abstract The ovary is one of the first organs to show overt signs aging in human body, and ovarian associated with a loss gamete quality quantity. age-dependent decline function contributes infertility an altered endocrine milieu, which has ramifications for overall health. microenvironment becomes fibro-inflammatory stiff age, this implications physiology pathology, including follicle growth, quality, ovulation dynamics, cancer. Thus, developing non-invasive tool measure monitor stiffness would represent major advance female reproductive health longevity. Shear wave elastography quantitative ultrasound imaging method evaluation soft tissue stiffness. been used clinically assessment liver fibrosis characterization tendinopathies various neoplasms thyroid, breast, prostate, lymph nodes as diagnostic prognostic tool. In study, we review underlying principles shear its current clinical uses outside tract well successful application tissues, uterus cervix. We also describe emerging use technology via transvaginal ultrasound. Establishing biomarker may have predicting reserve outcomes Assisted Reproductive Technologies efficacy therapeutics extend This parameter broad relevance other conditions where be implicated, such polycystic syndrome, late off target effects chemotherapy radiation, premature insufficiency, differences sexual development, Summary sentence: Wave Elastography technique study stiffness, here applications disease.

Language: Английский

Citations

6
Analysis of cell–cell interaction between mural granulosa cells and cumulus granulosa cells during ovulation using single‐cell RNA sequencing data of mouse ovary DOI
Yuichiro Shirafuta, Isao Tamura,

Amon Shiroshita

et al.

Reproductive Medicine and Biology, Journal Year: 2024, Volume and Issue: 23(1)

Published: Jan. 1, 2024

We investigated the interactions between mural granulosa cells (MGCs) and cumulus (CGCs) during ovulation after LH surge.

Language: Английский

Citations

5
A High-resolution N-Glycoproteome Landscape of Aging Mouse Ovary DOI Creative Commons

Yongqi Wu,

Zhi‐Da Zhang, Yong‐Chao Xu

et al.

Redox Biology, Journal Year: 2025, Volume and Issue: 81, P. 103584 - 103584

Published: March 7, 2025

Ovarian aging typically precedes the decline of other organ systems, yet its molecular mechanisms remain poorly understood. Glycosylation as one most important protein modifications has been especially unexplored in this context. Here, we present first high-resolution glycoproteomic landscape mouse ovaries, uncovering site-specific N-glycan signatures across subcellular components such high proportions complex glycans, core fucosylation, and LacdiNAc branches at zone pellucida. We report three major glycosylation alterations aged ovaries: frequently changed core-fucosylation associated with cell adhesion immune responses, decreased glycans on zona pellucida (ZP) responsible for fertility decline, increased sialylated modified by Neu5Ac Neu5Gc playing different roles activation responses. Integrated multi-omic analyses further highlight unique role glycosylation, distinct from phosphorylation, regulating key signaling pathways, antigen processing presentation, complement coagulation cascades, ROS biosynthetic metabolic processes, well death. This study offers a novel glycobiological perspective ovarian aging, broadening our understanding beyond traditional approaches.

Language: Английский

Citations

0
Follicular metabolic dysfunction, oocyte aneuploidy and ovarian aging: a review DOI Creative Commons

Depei Wu,

Chuanming Liu, Lijun Ding

et al.

Journal of Ovarian Research, Journal Year: 2025, Volume and Issue: 18(1)

Published: March 12, 2025

With the development of modern society and prolonged education, more women choose to delay their childbearing age, which greatly increases number aged older than 35 years with needs. However, increasing quantity quality oocytes continue fall, especially aneuploidy, leads a low in vitro fertilization (IVF) success rate, high abortion rate teratogenesis assisted reproduction advanced maternal age. In addition genetics epigenetics, follicular metabolism homeostasis is closely related ovarian aging oocyte aneuploidy. Glucose, lipid, amino acid not only provide energy for follicle genesis but also regulate maturation. This review focuses on relationships among metabolism, discusses potential therapeutic metabolites aging.

Language: Английский

Citations

0