ArticleCell death & disease2021
DNA methylation mediated RSPO2 to promote follicular development in mammals.
Article in Cell death & disease, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 35 citations in OpenAlex.
- The Removal of H3K27me3 PromotedCells · 2026Article
- Nanopore long-read RNA sequencing reveals key genes regulating pre-hierarchical follicle development in the chicken ovary.Poultry science · 2026Article
- Epigenetic deciphering of ovarian aging: multilayer interactive mechanisms and targeted reversal strategies.Epigenetics & chromatin · 2026Review
- OGDH mediates α-ketoglutarate-induced follicular development and antioxidative response by interacting with CAT/SOD2.Biological research · 2026Article
- DNMT/TET Imbalance and Network-Level DNA Methylation Remodeling in Ovarian Aging: Mechanistic Perspectives.Biology · 2026Review
- Metabolomics and Lipidomics in the Study of Reproductive Performance in Livestock.Animals : an open access journal from MDPI · 2026Review
- CNOT3 resists ovarian aging by accelerating oocyte maturation and promoting ESCs differentiation.Stem cell research & therapy · 2026Article
- Effects of L-citrulline supplementation in the basal diet on reproductive performance, serum metabolites, and microbial community structure in Simmental cows.Frontiers in microbiology · 2026Article
- Article
- Hypo-glycosylated FSH enhances the ovarian microenvironment for follicular development compared to fully glycosylated FSH.Cell communication and signaling : CCS · 2025Article
- FGA, a new target of histone acetylation, inhibits apoptosis of granulosa cells in follicles.Biological research · 2025Article
- DNA Methylation Mediates the Transcription ofCells · 2025Article
- Pyruvate Regulates the Expression ofCells · 2025Article
- Article
- TET1 overexpression affects cell proliferation and apoptosis in aging ovaries.Journal of assisted reproduction and genetics · 2024Article
- The assembly and activation of the PANoptosome promote porcine granulosa cell programmed cell death during follicular atresia.Journal of animal science and biotechnology · 2024Article
- Increased DNMT1 acetylation leads to global DNA methylation suppression in follicular granulosa cells during reproductive aging in mammals.BMC genomics · 2024Article
- The antisense lncRNA of TAB2 that prevents oxidative stress to enhance the follicular growth in mammals.Communications biology · 2024Article
- Knockdown ofInternational journal of molecular sciences · 2024Article
- Visfatin Affects the Transcriptome of Porcine Luteal Cells during Early Pregnancy.International journal of molecular sciences · 2024Article
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
In female mammals, the proliferation, apoptosis, and estradiol-17β (E2) secretion of granulosa cells (GCs) have come to decide the fate of follicles. DNA methylation and RSPO2 gene of Wnt signaling pathway have been reported to involve in the survival of GCs and follicular development. However, the molecular mechanisms for how DNA methylation regulates the expression of RSPO2 and participates in the follicular development are not clear. In this study, we found that the mRNA and protein levels of RSPO2 significantly increased during follicular development, but the DNA methylation level of RSPO2 promoter decreased gradually. Inhibition of DNA methylation or DNMT1 knockdown could decrease the methylation level of CpG island (CGI) in RSPO2 promoter and upregulate the expression level of RSPO2 in porcine GCs. The hypomethylation of -758/-749 and -563/-553 regions in RSPO2 promoter facilitated the occupancy of transcription factor E2F1 and promoted the transcriptional activity of RSPO2. Moreover, RSPO2 promoted the proliferation of GCs with increasing the expression level of PCNA, CDK1, and CCND1 and promoted the E2 secretion of GCs with increasing the expression level of CYP19A1 and HSD17B1 and inhibited the apoptosis of GCs with decreasing the expression level of Caspase3, cleaved Caspase3, cleaved Caspase8, cleaved Caspase9, cleaved PARP, and BAX. In addition, RSPO2 knockdown promoted the apoptosis of GCs, blocked the development of follicles, and delayed the onset of puberty with decreasing the expression level of Wnt signaling pathway-related genes (LGR4 and CTNNB1) in vivo. Taken together, the hypomethylation of -758/-749 and -563/-553 regions in RSPO2 promoter facilitated the occupancy of E2F1 and enhanced the transcription of RSPO2, which further promoted the proliferation and E2 secretion of GCs, inhibited the apoptosis of GCs, and ultimately ameliorated the development of follicles through Wnt signaling pathway. This study will provide useful information for further exploration on DNA-methylation-mediated RSPO2 pathway during follicular development.
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