Epigenetic profiling of mouse uteri across reproductive aging
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ABSTRACT:
PROVIDER: PRJNA1271427 | ENA |
REPOSITORIES: ENA
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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:The testis, efferent ductules, epididymis, and vas deferens, constituting the majority of male reproductive tract, are the regions for testosterone production, spermatogenesis, and sperm maturation, storage and discharge, but whether these regions change during aging is unknown. Here, we addressed this by investigating the adult (3-month) and aged (18-month) transcriptomes from seven regions of male mouse reproductive tract：the testis, efferent ductules, initial segment, caput, corpus and cauda epididymis, and vas deferens. We identified various of region-specific genes across different regions of male mouse reproductive tract. Moreover, we identified region-dependent changes of transcripts at an anatomic resolution. This study provides a framework for futher studies on male reproducitve aging.
2022-03-02 | GSE181426 | GEO
Project description:Epigenetic Biomarkers of Aging
| PRJNA875201 | ENA
Project description:Epigenetic Biomarkers of Aging
| PRJNA875202 | ENA
Project description:Reproductive cessation is perhaps the earliest aging phenotypes humans experience. Similarly, C. elegans' reproduction ceases in mid-adulthood. Although somatic aging has been studied in both worms and humans, mechanisms regulating reproductive aging are not yet understood. Here we show that TGF-beta Sma/Mab activity regulates reproductive aging transcriptionally separable from its regulation of body size growth. This SuperSeries is composed of the following subset Series: GSE23446: Reproductive aging: sma-2;fem-1 day 8 oocyte vs fem-1 day 8 oocyte GSE23447: Reproductive aging: fem-1 day 3 oocyte vs fem-1 day 8 oocyte GSE23448: Body size regulation and TGF-beta Sma/Mab pathway: sma L4 vs N2 L4 Refer to individual Series
2010-09-01 | E-GEOD-23509 | biostudies-arrayexpress
Project description:Mouse uteri at gestation day 13
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Project description:We investigated the contentious role of mitochondrial reactive oxygen species (ROS) on mitochondrial DNA (mtDNA) quality and quantity in female reproductive aging. By conditionally knocking out the Sod2 gene in female mouse germline, we observed increased mitochondrial ROS and decreased oocyte quality, primarily due to impacts on OXPHOS complex II and mtDNA encoded mRNA levels. Interestingly, we found no increased mtDNA mutations, but alterations in mtDNA quantity, indicating the susceptibility of mtDNA to the mitochondrial ROS during reproductive aging. Notably, when we further decreased the basal level of mtDNA quantity by deactivating the mtSSB protein in Sod2 conditional knockout females, we observed an exacerbation of reproductive aging effects. This highlights the crucial role of mtDNA quantity in mitigating the impact of oxidative stress on fertility.
2024-09-09 | GSE251734 | GEO
Project description:To find genes in C. elegans oocytes associated with reproductive aging.
2010-09-01 | GSE23447 | GEO
Project description:This SuperSeries is composed of the following subset Series: GSE32050: 5-hydroxymethylcytosine-mediated epigenetic dynamics during neurodevelopment and aging [5hmC Capture and Seq] GSE32187: 5-hydroxymethylcytosine-mediated epigenetic dynamics during neurodevelopment and aging [mRNA profiling] Refer to individual Series
2011-10-29 | E-GEOD-32188 | biostudies-arrayexpress
Project description:To find genes in C. elegans oocytes associated with reproductive aging. Five replicates comparing RNA from oocyte samples collected from day 3 fem-1(hc17) animals with RNA from oocyte samples collected from day 8 fem-1(hc17) animals. Three out of five are dye-flipped.
2010-09-01 | E-GEOD-23447 | biostudies-arrayexpress