Single-Cell RNA Sequencing Reveals Peripheral Immune Cell Senescence and Inflammatory Phenotypes in Patients with Premature Ovarian Failure

Journal of Inflammation Research, Journal Year: 2025, Volume and Issue: Volume 18, P. 2699 - 2715

Published: Feb. 1, 2025

Premature Ovarian Failure (POF) is a heterogeneous syndrome characterized by ovarian dysfunction, frequently associated with autoimmune factors. The interaction between peripheral and immune signals remains unclear. Recent advancements in single-cell technology provide unique opportunity to examine the complex response POF patients at microstructural level. This study investigates microenvironment's complexity through local responses. Peripheral blood mononuclear cells (PBMCs) were isolated from three healthy individuals four patients. Single-cell RNA sequencing (scRNA-seq) was used delineate cell clusters identify differentially expressed genes (DEGs). Enrichment, SCENIC, pseudo-time analyses utilized explore cellular phenotype diversity, regulatory patterns, evolutionary trajectories. A mouse model for validation. Seven identified classified into two groups. exhibited increased proportions T cells, NK B as well upregulated IGLC2, GNLY, GZMB, FCGR3A, CCL5 expressions compared controls. Monocytes, particularly non-classical monocytes, inflammatory phenotypes. CD8+ Effector demonstrated cytotoxicity TCR clonal expansion. trajectory of involved synchronous upregulation cytotoxic-related checkpoint molecules. Notably, CCL5, primarily produced emerged critical factor. Elevated levels plasma ovaries, along infiltration, suggested its potential role chemotaxis damage POF. Validation further supported these findings. In summary, this provides in-depth insights landscape POF, revealing distinct populations, pathways, signaling networks linked disease. These findings enhance our understanding POF's immunological mechanisms, contributing development diagnostic therapeutic strategies.

Language: Английский

---

Reduced DNMT1 expression associated with TP53 promoter hypomethylation mediate enhanced granulosa cell senescence during ovarian aging

Gynecological Endocrinology, Journal Year: 2025, Volume and Issue: 41(1)

Published: Feb. 26, 2025

Background The effects of granulose cell (GC) senescence on premature ovarian insufficiency/premature failure have been extensively examined, the association between GC and aging remains to be clarified.

Language: Английский

---

Multi-omics analysis of the dynamic role of STAR+ cells in regulating platinum-based chemotherapy responses and tumor microenvironment in serous ovarian carcinoma

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 16

Published: March 3, 2025

Background Serous ovarian carcinoma (SOC) is the most lethal subtype of cancer, with chemoresistance to platinum-based chemotherapy remaining a major challenge in improving clinical outcomes. The role tumor microenvironment (TME), particularly cancer-associated fibroblasts (CAFs), modulating responses not yet fully understood. Methods To explore relationship between CAF subtypes and sensitivity, we employed single-cell RNA sequencing (scRNA-seq), bulk RNA-seq, spatial transcriptomics, immunohistochemistry (IHC), immunofluorescence (IF). This multi-omics approach enabled identification, characterization, functional analysis both chemotherapy-sensitive chemotherapy-resistant SOC patients. Results We identified steroidogenic acute regulatory protein-positive (STAR+) cells as novel enriched STAR + exhibited unique transcriptional profiles were functionally pathways related P450 drug metabolism, lipid amino acid enhanced pathway activity observed groups. Spatial transcriptomics IF revealed that closely localized cells, suggesting potential cell-cell interactions. Further communication indicated may suppress WNT signaling contributing improved responses. Importantly, expression levels, validated by IHC, positively correlated sensitivity patient prognosis. Platinum-based was shown increase proportion underscoring their dynamic response treatment. Conclusion Our study identifies enhances SOC. By key metabolic potentially suppressing signaling, could contribute treatment These findings position promising biomarker for predicting efficacy SOC, which warrants further investigation.

Language: Английский

---

Comparative analysis of human and mouse ovaries across age

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: March 3, 2025

Abstract Mouse is a tractable model for human ovarian biology, however its utility limited by incomplete understanding of how transcription and signaling differ interspecifically with age. We compared ovaries between species using 3D-imaging, single-cell transcriptomics, functional studies. In mice, we mapped declining follicle numbers oocyte competence during aging; in ovaries, identified cortical pockets density changes. Oocytes had species-specific gene expression patterns growth that converged toward maturity. Age-related transcriptional changes were greater oocytes than granulosa cells across species, although mature change more humans. sympathetic nerves glia; nerve increased aged and, when ablated perturbed folliculogenesis. This comparative atlas defines shared hallmarks biology.

Language: Английский

---

CCDC134 enhances ovarian reserve function and angiogenesis by directly interacting with INHA in a mouse model of premature ovarian insufficiency

APOPTOSIS, Journal Year: 2025, Volume and Issue: unknown

Published: March 5, 2025

Language: Английский

---

Regulation of Female Reproductive Aging by the Spag17 Gene

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: March 6, 2025

ABSTRACT Reproductive aging in females is characterized by a decline oocyte quantity and quality, as well uterine cervical dysfunction that contributes to infertility pregnancy complications. To investigate mechanisms underlying reproductive aging, we explored the contribution of Spag17 , cilia-related gene associated with tissue homeostasis fibrosis. was expressed throughout female tract; however, its expression declined age ovarian tissue, while high levels were observed cervix young during remodeling pre- post-parturition periods. Loss mice resulted impaired fertility, obstructed labor, maternal death. This phenotype accelerated increased fibrosis, stiffness, further complicating parturition. At molecular level, loss activated key aging-associated pathways, including proinflammatory, profibrotic, senescence signaling, suggesting SPAG17 may be critical player aging. TEASER modulator

Language: Английский

---

A Single‐Cell Transcriptome Atlas Characterizes the Immune Landscape of Human Testes During Aging

Aging Cell, Journal Year: 2025, Volume and Issue: unknown

Published: March 6, 2025

Aging disrupts immune regulation, affecting tissue function and increasing vulnerability to various diseases. However, the effects of aging on cells within human testes are not well understood. In this study, we utilized single-cell RNA sequencing profile from 33 testis samples individuals aged 21 69. Our analysis revealed key cell types, including CD8+ T cells, monocytes, cDC2 macrophage subtypes testes. We observed an age-related change in monocytes MRC1hi tissue-resident (TRM), a pattern consistent both mouse Individuals 40 older showed notable shifts pathways related phagocytosis, cytokine signaling, antigen presentation. Monocytes also exhibited pro-inflammatory characteristics, potentially contributing low-grade inflammation commonly associated with aging. Together, these findings provide insights into alterations uncover molecular mechanisms underlying shifts, offering valuable resource for understanding reproductive system.

Language: Английский

---

Single-cell resolution reveals the cell types and transcriptomic landscape of the ovary in mandarin fish (Siniperca chuatsi)

Aquaculture, Journal Year: 2025, Volume and Issue: unknown, P. 742430 - 742430

Published: March 1, 2025

Language: Английский

---

Ovarian vascular aging: a hidden driver of mid-age female fertility decline

npj Aging, Journal Year: 2025, Volume and Issue: 11(1)

Published: March 30, 2025

Although ovarian reserve remains sufficient, function declines in mid-age, leading to reduced fertility around age 35, with the causes remaining unclear. Recent studies highlight vascular aging as a key factor this decline, age-related reductions remodeling disrupting oocyte development. Salidroside, natural compound that reverses and promotes angiogenesis, presents promising strategy rejuvenate health enhance fertility, offering potential for preserving reproductive aged women.

Language: Английский

---

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

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

Published: April 4, 2025

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

---