Loss of oocyte Rps26 in mice arrests oocyte growth and causes premature ovarian failure. Issue 12 (December 2018)

• Record Type: Journal Article
• Authors: Liu, Xiao-Man; Yan, Ming-Qi; Ji, Shu-Yan; Sha, Qian-Qian; Huang, Tao; Zhao, Han; Liu, Hong-Bin; Fan, Heng-Yu; Chen, Zi-Jiang
• Is Part Of: Cell death and disease. Volume 9:Issue 12(2018)
• Page Start: 1
• Page End: 15
• Publication Date: 2018-12
• Subjects: Cell death -- Periodicals; Apoptosis -- Periodicals; 571.936
• DOI: 10.1038/s41419-018-1196-3
• Languages: English
• ISSNs: 2041-4889

Abstract

Abstract Global transcriptional activity increases as oocytes grow and is silenced in fully grown oocytes. Thus, the chromatin configuration varies during oocyte growth, but the molecular mechanisms regulating these changes remain to be clarified. Here, we studied a susceptibility gene of polycystic ovary syndrome (PCOS), RPS26, which is a ribosomal protein-encoding gene that is highly expressed in the ovary, but the functions of which remain unknown. Specific knockout ofRps26 in mouse oocytes resulted in retarded follicle development from pre-antral follicles to antral follicles, while the chromatin configurations of the oocytes were arrested at the transition from the non-surrounded nucleolus (NSN) to surrounded nucleolus (SN)-type. As a consequence, all oocytes died by postnatal day 84 resulting in premature ovarian failure (POF). Loss ofRps26 in oocytes led to decreased mRNA transcription and low levels of histone trimethylation on H3K4/H3K9 and DNA methylation at 5-cytosine, high levels of which are required for oocytes to transform from NSN to SN-type. Low protein levels of oocyte-derived growth differentiation factor 9, bone morphogenetic protein 15, and the oocyte-granulosa cell gap junction protein connexin 37 inhibited oocyte growth and retarded follicle development. The disruption of the phosphoinositide 3-kinase/protein kinase B/Forkhead box O-3a pathway contributed to oocyte death and follicle atresia. These results provide genetic clues for the clinical diagnosis of POF, especially in PCOS patients without treatment.