Theophylline derivatives promote the activation of primordial follicles and ameliorate fertility deficits in naturally aged mice
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PROVIDER: PRJNA1099590 | ENA |
REPOSITORIES: ENA
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Project description:The residual dormant primordial follicles in aged women and patients with premature ovarian insufficiency (POI) are difficult to activate in vivo. In this study, we found that PDE1A, PDE2A and PDE6D were expressed mainly in mouse primordial follicle oocytes and that PDE1A and PDE2A levels were significantly decreased during the activation of primordial follicles. The specific inhibitors of PDE1 (nimodipine), PDE2 (EHNA) and PDE5/6 (zaprinast) and the nonspecific PDE inhibitors theophylline derivatives (including aminophylline, dyphylline, enprofylline, choline theophyllinate, doxofylline, arofylline and lisofylline) activated mouse primordial follicles. These inhibitors also increased the levels of cyclic adenosine monophosphate (cAMP) and phosphorylated protein kinase B (p-Akt) in cultured mouse ovaries. Moreover, the administration of aminophylline, dyphylline and enprofylline to neonatal mice by intraperitoneal injection and to adolescent mice by oral treatment increased the number of growing follicle and the levels of p-Akt in the ovaries. Importantly, the oral administration of aminophylline increased the quantity and quality of ovulated oocytes and the number of offspring in naturally aged mice. In addition, aminophylline, dyphylline and enprofylline activated human primordial follicles and increased p-Akt levels. Thus, theophylline derivatives activate primordial follicles by increasing cAMP levels and activating the PI3K/Akt pathway, and the oral administration of aminophylline increases fertility in naturally aged female mice. As oral medications, theophylline derivatives may be used to increase fertility in aged women and patients with POI.
2024-05-30 | GSE263843 | GEO
Project description:We found MnCl2 and ZnSO4 promoted the activation of mouse primordial follicles through glycosis-dependent mTOR pathway in granulosa cells and PI3K/Akt pathway in oocytes. We further analyzed the transcriptome changes in the ovaries after MnCl2 and ZnSO4 treatments.
2023-05-27 | GSE232350 | GEO
Project description:Women are born with millions of primordial follicles which gradually decrease with increasing age and this irreversible supply of follicles completely exhausts at menopause. The fertility capacity of women diminishes in parallel with aging. The mechanisms for reproductive aging are not fully understood. In our recent work we observed a decline in BRCA1 mediated DNA repair in aging rat primordial follicles. To further understand the age-related molecular changes, we performed microarray gene expression analysis using total RNA extracted from immature (18â20 days) and aged (400â450 days) rat primordial follicles. The results of current microarray study revealed that there were 1011 (>1.5 fold, p<0.05) genes differentially expressed between two groups in which 422 genes were up-regulated and 589 genes were down-regulated in aged rat primordial follicles compared to immature. The gene ontology and pathway analysis of differentially expressed genes revealed a critical biological function such as cell cycle, oocyte meiosis, chromosomal stability, transcriptional activity, DNA replication and DNA repair were affected by age and this considerable difference in gene expression profiles may have adverse influence on oocyte quality. Our data provide information on the processes that may contribute to aging and age-related decline in fertility. In total of 6 samples, 3 replicate samples were from immature rat primordial follicles and 3 replicate samples were from aged rat primordial follicles. For each replicate sample, the primordial follicles isolated from multiple isolations (each time 10-20 rat ovaries) were finally pooled in order to get required quantity of RNA.
2016-07-18 | E-GEOD-84333 | biostudies-arrayexpress
Project description:Women are born with millions of primordial follicles which gradually decrease with increasing age and this irreversible supply of follicles completely exhausts at menopause. The fertility capacity of women diminishes in parallel with aging. The mechanisms for reproductive aging are not fully understood. In our recent work we observed a decline in BRCA1 mediated DNA repair in aging rat primordial follicles. To further understand the age-related molecular changes, we performed microarray gene expression analysis using total RNA extracted from immature (18–20 days) and aged (400–450 days) rat primordial follicles. The results of current microarray study revealed that there were 1011 (>1.5 fold, p<0.05) genes differentially expressed between two groups in which 422 genes were up-regulated and 589 genes were down-regulated in aged rat primordial follicles compared to immature. The gene ontology and pathway analysis of differentially expressed genes revealed a critical biological function such as cell cycle, oocyte meiosis, chromosomal stability, transcriptional activity, DNA replication and DNA repair were affected by age and this considerable difference in gene expression profiles may have adverse influence on oocyte quality. Our data provide information on the processes that may contribute to aging and age-related decline in fertility.
2016-07-18 | GSE84333 | GEO
Project description:The metallic compound promotes primordial follicle activation and ameliorates fertility deficits in aged mice
| PRJNA971656 | ENA
Project description:Transcriptomic analysis reveals the anti-excessive lipogenesis and anti-inflammatory effects of SQ and its derivatives on preadipocyte differentiation We horizontally compared the effects of SQ and its four derivatives on preadipocyte differentiation and anti-inflammation. Di- and tetra-SQ can significantly improve the lipid metabolism function and anti-inflammatory effect of adipocytes, and ameliorate excessive production.
2023-02-18 | GSE224049 | GEO
Project description:Gene expression analysis of yw follicles at S9/10a, S10B, S12, and S14; Gene expression analysis of pxt mutant follicles (f01000 and EY03052) at S10B, S12, S14 Drosophila ovarian follicles complete development using a spatially and temporally controlled maturation process in which they resume meiosis and secrete a multi-layered, protective eggshell before undergoing arrest and/or ovulation. Microarray analysis revealed more than 150 genes that are expressed in a stage-specific manner during the last 24 hours of follicle development. These include all 30 previously known eggshell genes, as well as 19 new candidate chorion genes and 100 other genes likely to participate in maturation. Mutations in pxt, encoding a putative Drosophila cyclooxygenase, cause many transcripts to begin expression prematurely, and are associated with eggshell defects. Somatic activity of Pxt is required, as RNAi knockdown of pxt in the follicle cells recapitulates both the temporal expression and eggshell defects. One of the temporally regulated genes, cyp18a1, which encodes a cytochromome P450 protein mediating ecdysone turnover, is downregulated in pxt mutant follicles, and cyp18a1 mutation itself alters eggshell gene expression. These studies further define the molecular program of Drosophila follicle maturation and support the idea that it is coordinated by lipid and steroid hormonal signals. minimum of 2 replicates per stage and genotype. yw=control follicles. pxt=mutant follicles.
2011-06-09 | E-GEOD-29815 | biostudies-arrayexpress
Project description:To gain insight into the differentially expressed genes (DEGs) and signalling pathways regulating development of small follicles (SF diameter ≥3 mm to <6 mm) into large follicles (LF diameter ≥6 mm) in Ghoongroo pigs, a comprehensive transcriptome profiling of porcine follicles was conducted using NovaSeq600 sequencing platform. The DEGs were identified using DESeq2 with threshold of padj <0.05 and log2 Fold Change cut off 0.58. Functional annotations and bioinformatics analysis of the DEGs were performed to find out biological functions, signalling pathways and hub genes regulating follicular development and function.
2023-11-08 | GSE228787 | GEO
Project description:we compared the phosphoproteomes of SY and F6 follicles in laying hens and identified several genes involved in chicken follicle selection.
2022-09-01 | PXD029503 | Pride
Project description:Mobilization of endogenous retrotransposons can destabilize the genome, an imminent danger during epigenetic reprogramming of cells in the germline. The P-element-induced wimpy testis (PIWI)-interacting RNA (piRNA) pathway is known to silence retrotransposons in the mouse testes. Several piRNA pathway components localize to the unique, germline structure known as the nuage. In this study, we surveyed mouse ovaries and found, for the first time, transient appearance of nuage-like structures in oocytes of primordial follicles. Mouse vasa homolog (MVH), Piwi-like 2 (PIWIL2/MILI) and tudor domain-containing 9 (TDRD9) are present in these structures, whereas aggregates of germ cell protein with ankyrin repeats, sterile alpha motif and leucine zipper (GASZ) localize separately in the cytoplasm. Retrotransposons are silenced in primordial ovarian follicles, and de-repressed upon reduction of piRNA expression in Mvh, Mili or Gasz mutants. However, these null-mutant females, unlike their male counterparts, are fertile, uncoupling retrotransposon activation from sterility.
| S-EPMC4067262 | biostudies-literature