Progression of uterine aging in mice
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1260992 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Reproductive decline with advanced maternal age is majorly driven by functional changes to the uterus in mice. Here, we conducted an aging time course series in female mice and assessed changes to the uterine transcriptomes between young females and those aged between 24 weeks and 52 weeks and over. We also assessed the impact of key candidates of aging driver genes in the human endometrial Ishikawa cell line. Our results show an increase in transcriptional heterogeneity in the uterus as a function of maternal age. However, these changes are largely distinct from organismal aging and highlight that aging of reproductive tissues, notably the endometrium, is driven by a unique set of aging driver genes.
2025-08-07 | GSE296745 | GEO
Project description:Uterine-specific SIRT1 deficiency confers premature uterine aging and impairs invasion and spacing of blastocyst and stromal cell decidualization in mice.
| PRJNA772264 | ENA
Project description:Advanced maternal age increases the risk of pregnancy complications because of a higher incidence of karyotypic imbalances in the oocyte. A very important yet much less explored contribution to this risk, however, is the declining capacity of the uterus to adapt to the hormonal stimulus of pregnancy. As such, it has remained unknown what drives the uterine aging phenotype on the molecular and cellular level. Here, we show in mice that maternal aging is associated with a progressive increase in transcriptional variation that is accompanied by a drastic accumulation of activating histone marks. Importantly, the transcriptional signatures associated with uterine aging differ substantially from those of organismal aging. Single-cell deconvolution analysis demonstrates that maternal age-induced effects originate in the epithelial compartment and specifically entail a dramatic up-regulation of the pioneer transcription factor FOXC1, linked to an accumulation of H3K4me3 and H3K27ac across the locus. FOXC1 over-expression in human endometrial cells causes profound transcriptomic shifts and increases proliferation rates, recapitulating the aging phenotype. Using endometrial epithelial organoids of young and aged mice, we find that aging hallmarks including Foxc1 up-regulation and H3K27ac hyper-enrichment are conserved in vitro. In line with the epithelial hyperplasia phenotype seen in vivo, endometrial epithelial organoids from aged mice are larger and mis-express key factors critical for uterine gland maturity and function, most notably SOX9. Collectively, our data highlight the specific susceptibility of uterine epithelial cells to early-onset aging, with early changes manifesting in an increase in activating epigenetic marks that coalesce on the mis-regulation of FOXC1.
2025-08-11 | GSE298816 | GEO
Project description:Loss of LOXL2 promotes uterine hypertrophy and tumor progression
| PRJNA882816 | ENA
Project description:Uterine leiomyomas (ULs, or fibroids) are the most prevalent clinically significant tumors in reproductive-aged women, frequently causing abnormal uterine bleeding, pelvic pain, and infertility. Although surgical resection is effective for these benign neoplasms, the development of non-invasive, targeted therapies is an urgent clinical need. To bridge the gap between genotype and phenotype in ULs, we employed an integrated multi-omics strategy focused on the recurrent MED12 p.G44D mutation.
2025-12-18 | MSV000100276 | MassIVE
Project description:Placental aging has been proposed to promote labor onset, but specific mechanisms remain elusive. An unbiased transcriptomic analysis of healthy mouse placenta revealed that hypoxia-inducible factor 1 (HIF-1) stabilization is a hallmark of advanced gestational timepoints, accompanied by mitochondrial dysfunction and cellular senescence. We validated these gestational age-associated changes through similar findings in human placenta. In parallel in primary mouse trophoblasts and human choriocarcinoma JAR cells, we modeled HIF-1 induction using prolyl hydroxylase inhibitors cobalt chloride (CoCl2) and dimethyloxalylglycine (DMOG), and demonstrated that mitochondrial dysfunction and cellular senescence occur secondary to HIF-1 stabilization. Whole transcriptome analysis revealed that HIF-1 stabilization in JAR cells recapitulated the dysregulation of several pathways observed in aged placenta. Further, conditioned media from cultured trophoblasts following HIF-1 induction is sufficient to induce a contractile phenotype in immortalized uterine myocytes, suggesting a mechanism by which the aging placenta may help drive the transition from uterine quiescence to contractility at the onset of labor.
2022-03-29 | GSE199278 | GEO
Project description:To gain insight into the mechanism(s) by which obesogenic diet caused decreased uterine contractility at term, we collected uterine tissue from mice fed either a control (CON) or an obesogenic (DIO) diet at day 18.5 of pregnancy and performed RNA sequencing.
2024-05-28 | GSE268397 | GEO
Project description:To identify genes differentially expressed in the glandless uterus, whole uteri were collected from control (uterine glands present) and PUGKO (no uterine glands) mice at day of pseudopregnancy (DOPP) 3.5 (day DOPP 0.5= vaginal plug). Microarray analysis identified differentially expressed genes in the glandless uteri of PUGKO mice as compared to control mice.
2013-11-05 | GSE48340 | GEO
Project description:At birth, all female mice, including those that either lack estrogen receptor α (ERα-knockout) or that express mutated forms of ERα (AF2ERKI), have a hypoplastic uterus. However, uterine growth and development that normally accompanies pubertal maturation does not occur in ERα-knockout or AF2ERKI mice, indicating ERα mediated estrogen signaling is essential for this process. Mice that lack Cyp19 (aromatase, ArKO mice), an enzyme critical for estrogen (E2) synthesis, are unable to make E2, and lack pubertal uterine development. A single injection of E2 into ovariectomized adult (10 weeks old) females normally results in uterine epithelial cell proliferation, however, we observe that, although ERα is present in the ArKO uterine cells, no proliferative response is seen. We assessed the impact of exposing ArKO mice to E2 during pubertal and post-pubertal windows and observed that E2 exposed ArKO mice acquired growth responsiveness. Analysis of differential gene expression between unexposed ArKO samples and samples from animals exhibiting the ability to mount an E2-induced uterine growth response (WT or E2 exposed ArKO) revealed activation of EZH2 and HAND2 signaling and inhibition of GLI1 responses. EZH2 and HAND2 are known inhibit uterine growth, and GLI1 is involved in IHH signaling, which is a positive mediator of uterine response. Finally, we show that exposure of ArKO females to dietary phytoestrogens results in their acquisition of uterine growth competence. Altogether our findings suggest that pubertal levels of endogenous and exogenous estrogens impact biological function of uterine cells later in life via ERα-dependent mechanisms. We compared uterine RNA from ovariectomized adult aromatase knockout mice (ARKO) mice that were untreated to WT mice and to ARKO that were administered estradiol benzoate (EB) to induce uterine epithelial cell growth competence
2020-04-29 | GSE147900 | GEO