Objectives: Studies have demonstrated that B lymphoma Mo-MLV insertion region 1 (BMI1) plays an important role in male reproductive function and the regulation of spermatogonia proliferation. However, whether BMI1 exerts a similarly important function in spermatocyte development remains unclear.
Methods: In this study, we investigated the role of BMI1 in spermatocyte development using a mouse spermatocyte-derived cell line (GC-2) and a -knockout (KO) mouse model.
Results: We demonstrated that BMI1 promoted the proliferation and inhibited the apoptosis of GC-2 cells. Mechanistically, we presented and evidence showing that BMI1 binds to the promoter region of the forkhead box L1 () gene, sequentially driving chromatin remodeling and gene silencing. BMI1, which functions as a classical polycomb protein, was found to direct the transcriptional repression of through increasing the H2AK119ub level and reducing that of H3K4me3 in the promoter region of . Our results further indicated that the knockdown of expression significantly enhanced cell proliferation activating β-catenin signaling in BMI1-deficient GC-2 cells.
Conclusions: Collectively, our study revealed for the first time the existence of an epigenetic mechanism involving BMI1-mediated gene silencing in GC-2 cells development and provided potential targets for the treatment of male infertility.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9185053 | PMC |
Publication Analysis
Top Keywords
Similar Publications
CircMYH9/miR-133a-3p/CXCR4 axis: a novel regulatory network in sperm fertilization and embryo development.
Mol Biomed
December 2024
Clinical Medicine Postgraduate Workstation, Soochow University, Xuzhou, 221009, China.
This study aimed to investigate the influence of sperm miRNAs on fertilization rates (FR) in in vitro fertilization (IVF) and to explore potential regulatory mechanisms in sperm-mediated fertilization and embryo development. Through high-throughput sequencing, we identified differentially expressed miRNAs in sperm, with miR-133a-3p significantly upregulated in samples associated with low FR and available embryo rate (AER). Key regulatory circRNAs and mRNAs were further identified via the Starbase database, intersected with differentially expressed RNA, and analyzed through GO, KEGG, and PPI analyses.
View Article and Find Full Text PDFProtective effect of trehalose on sperm chromatin condensation failure and semen quality decline in BDE-209-exposed mice.
Food Chem Toxicol
December 2024
Department of Occupational and Environmental Health, School of Public Health, Anhui Medical University, Hefei, 230032, China. Electronic address:
Article Synopsis
- BDE-209 exposure leads to male reproductive toxicity characterized by a decline in sperm quality, but the impact of autophagy in this process was not well understood.
- The study evaluated the protective effects of trehalose (Tre), an autophagy inducer, on reproductive damage during sperm development (spermiogenesis) caused by BDE-209 using a mouse model.
- Results showed that Tre improved various sperm qualities and reduced testicular damage, likely by restoring normal autophagy pathways via AMPK-ULK1 signaling, highlighting potential therapeutic targets for addressing male reproductive toxicity.
Oxidative and Endoplasmic Reticulum Stress Mediate Testicular Injury in a Rat Model of Varicocele.
Reprod Sci
December 2024
School of Life Sciences, Bengbu Medical University, 2600 Donghai Avenue, Bengbu, 233000, China.
Evidence of endoplasmic reticulum (ER) stress and activation of the unfolded protein response (UPR) have been increasingly reported in varicocele (VCL)-affected testes. However, the mechanisms by which oxidative stress (OS) and ER stress contribute to male infertility in VCL remain unclear. In this study, male Sprague-Dawley rats were divided into a control group, which underwent sham surgery, and a VCL group, in which VCL was surgically induced.
View Article and Find Full Text PDFMulti-omics revealed activation of TNF-α induced apoptosis signaling pathway in testis of DEHP treated prepubertal male rat.
Reprod Toxicol
November 2024
Department of Urology, Peking University First Hospital, Beijing 100034, China; Institution of Urology, Peking University, Beijing 100034, China; Beijing Key Laboratory of Urogenital Diseases (Male) Molecular Diagnosis and Treatment Center, Beijing 100034, China. Electronic address:
Article Synopsis
- The study investigates the harmful effects of di-(2-ethylhexyl) phthalate (DEHP) exposure on the testes of prepubertal rats, focusing on its impact on reproductive health.
- DEHP exposure led to decreased testis weight, increased oxidative stress, structural disorganization of testes, and reduced numbers of spermatogenic and Sertoli cells, along with damaged mitochondria.
- The research revealed that DEHP activates the TNF-α apoptosis pathway, resulting in impaired spermatogenesis and increased apoptosis, with similar effects observed using the active metabolite mono-(2-ethylhexyl) phthalate (MEHP) in vitro.
Deficiency in the Rab25 gene leads to a decline in male fertility and testicular injury: Impact on the regulation of germ cell proliferation and apoptosis.
Exp Cell Res
October 2024
Department of Urology Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, 400014, China; Chongqing Key Laboratory of Structural Birth Defect and Reconstruction, Chongqing, 400014, China; Chongqing Key Laboratory of Children Urogenital Development and Tissue Engineering, Children's Hospital of Chongqing Medical University, Chongqing, 400014, China; China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Children's Hospital of Chongqing Medical University, Chongqing, 400014, China. Electronic address:
Article Synopsis
- Rab25 is a regulatory protein involved in cellular transport, but its specific functions in male reproduction are still unclear.
- Researchers created a mouse model and a germ cell line to study Rab25's effects on testicular development, fertility, and cell behavior.
- The results showed that Rab25 is crucial for sperm production, with its absence leading to disorganized germ cells, reduced sperm quantity and motility, and increased cell death in the testes.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!