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.
Project description:To find genes downstream of the TGF-beta Sma/Mab pathway in C. elegans oocytes associated with reproductive aging. Eight replicates comparing RNA from oocyte samples collected from day 8 sma-2(e502);fem-1(hc17) animals with RNA from oocyte samples collected from day 8 fem-1(hc17) animals. Five out of eight are dye-flipped.
Project description:Advanced age is a primary risk factor for female infertility due to reduced ovarian reserve and declining oocyte quality. However, as an important contributing factor, the role of metabolic regulation during reproductive aging is poorly understood. Here, we applied untargeted metabolomics to identify spermidine as a critical metabolite in ovaries to protect oocytes against aging. In particular, we found that spermidine level was reduced in aged ovaries and supplementation of spermidine promoted follicle development, oocyte maturation, early embryonic development and female fertility of aged mice. By micro-transcriptomic analysis, we further discovered that recovery of oocyte quality by spermidine was mediated by enhancement of mitophagy activity and mitochondrial function in aged mice, and this action mechanism was conserved in porcine oocytes under oxidative stress. Altogether, our findings demonstrate that spermidine supplementation is a potentially effective strategy to ameliorate oocyte quality and reproductive outcome of women at an advanced age.
Project description:Chromosome segregation errors in oocytes lead to the production of aneuploid eggs, which are the leading cause of pregnancy loss and of several congenital diseases such as Down syndrome. The frequency of chromosome segregation errors in oocytes increases with maternal age, especially at a late stage of reproductive life. How aging at various life stages affects oocytes differently remains poorly understood. In this study, we describe aging-associated changes in the transcriptome profile of mouse oocytes throughout reproductive life. Our single-oocyte comprehensive RNA sequencing using RamDA-seq revealed that oocytes undergo transcriptome changes at a late reproductive stage, whereas their surrounding cumulus cells exhibit transcriptome changes at an earlier stage. Calorie restriction, a paradigm that reportedly prevents aging-associated egg aneuploidy, promotes a transcriptome shift in oocytes with the up-regulation of genes involved in chromosome segregation. This shift is accompanied by the improved maintenance of chromosomal cohesin, the loss of which is a hallmark of oocyte aging and causes chromosome segregation errors. These findings have implications for understanding how oocytes undergo aging-associated functional decline throughout their reproductive life in a context-dependent manner.
Project description:Chromosome aneuploidy increases in oocytes with maternal age, and is considered the leading cause for the increased incidence of infertility, miscarriage, and birth defects. Using mRNA-Sequencing of oocytes from 12 month old mouse versus 3 month young mouse, we identified a spindle assembly checkpoint gene, BubR1, whose expression was significantly decreased. We employed a mRNA microinjection based approach to increase BubR1 expression in aging oocytes. We find that increased expression of BubR1 protects against aneuploidy and chromosome misalignment in aging oocytes. After in vitro fertilization, the embryos derived from BubR1 increased expression aging oocytes exhibited chromosome stability as robust as those of the young ones. Furthermore, following embryo transfer, these embryos showed greatly improved developmental competency, with comparable levels of full-term development to those of the young ones. These results indicate that the decline in oocyte quality may be reversible and could lead to treatments that prolong female fertility. Examination of the effect of maternal aging on the mRNA expression in the mature oocytes of the female mice. Naturally ovulated mature oocytes (MII stage) were collected from 6 young (3 month) and 6 aging (12 month) female mice (3 oocytes per mice, 18 oocytes for each group).
Project description:The mechanisms contributing to age-related deterioration of the female reproductive system are complex but aberrant protein homeostasis is a major contributor. We elucidated the exceptionally stable proteins, structures, and macromolecules that persist in ovaries and gametes throughout the reproductive aging timeline in mammals. Ovaries exhibit localized structural and cell-type specific enrichment of stable macromolecules throughout both the follicular and extrafollicular environments. Moreover, both ovaries and oocytes harbor a panel of exceptionally long-lived proteins, including cytoskeletal components, mitochondrial, and oocyte-derived proteins. The exceptional persistence of these long-lived molecules might play a critical role in both lifelong maintenance and age-dependent deterioration of reproductive tissues.
Project description:We performed RNAseq analysis to determine the effect of MFN2 deletion on oocyte global gene expression profile. RNAseq revealed a total of 363 genes were significantly differentially expressed (p<0.05) in Mfn2-/- GV oocytes compared to WT (241 up-regulated and 122 down-regulated). Gene ontology (GO) analysis indicated significant over-representation of elements involved in regulation of embryonic development, cell death and survival, and cell morphology. Pathway analysis of top10 upregulated and downregulated annotated genes are listed. Our findings provide new insight into the role of MFN2 in the oocytes, and may help understand the potential mechanism of subfertility and reproductive aging associated with MFN2-deficiency.
Project description:We performed RNAseq analysis to determine the effect of MFN2 deletion on oocyte global gene expression profile. RNAseq revealed a total of 1041 genes were significantly differentially expressed (p<0.05) in Mfn2-/- seceondary follicle enclosed oocytes (SFOs) compared to WT, with 510 up-regulated and 531 down-regulated genes. GO cluster analysis indicated significant over-representation of elements involved in regulation of cell death and survival, cellular development and cellular growth. Pathway analysis of top10 upregulated and downregulated annotated genes are listed. Our findings provide new insight into the role of MFN2 in the oocytes, and may help understand the potential mechanism of subfertility and reproductive aging associated with MFN2-deficiency.
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