Death Processes in Bovine Theca and Granulosa Cells Modelled and Analysed Using a Systems Biology Approach

McEvoy, Malgorzata J.; Sinderewicz, Emilia; Creedon, Leo; McAfee, Marion; Jończyk, A.W.; Piotrowska-Tomala, K.K.; Skarzynski, Dariusz J.

doi:10.3390/ijms22094888

Cited by 8 publications

(5 citation statements)

References 56 publications

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“…POI is caused by defective primordial follicle pool formation, follicular recruitment/maturation, and accelerated follicular atresia. It has long been considered that granulosa cell death pathways, including apoptosis, necrosis and autophagy, are involved in follicular atresia [39][40][41][42][43][44] . However, detailed information on oocyte death during POI remains limited.…”

Section: Discussionmentioning

confidence: 99%

BNC1 deficiency-triggered ferroptosis through the NF2-YAP pathway induces primary ovarian insufficiency

Wang

Liu

et al. 2022

Nat Commun

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Primary ovarian insufficiency (POI) is a clinical syndrome of ovarian dysfunction characterized by premature exhaustion of primordial follicles. POI causes infertility, severe daily life disturbances and long-term health risks. However, the underlying mechanism remains largely unknown. We previously identified a Basonuclin 1 (BNC1) mutation from a large Chinese POI pedigree and found that mice with targeted Bnc1 mutation exhibit symptoms of POI. In this study, we found that BNC1 plays key roles in ovarian reserve and maintaining lipid metabolism and redox homeostasis in oocytes during follicle development. Deficiency of BNC1 results in premature follicular activation and excessive follicular atresia. Mechanistically, BNC1 deficiency triggers oocyte ferroptosis via the NF2-YAP pathway. We demonstrated that pharmacologic inhibition of YAP signaling or ferroptosis significantly rescues Bnc1 mutation-induced POI. These findings uncover a pathologic mechanism of POI based on BNC1 deficiency and suggest YAP and ferroptosis inhibitors as potential therapeutic targets for POI.

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Section: Discussionmentioning

confidence: 99%

BNC1 deficiency-triggered ferroptosis through the NF2-YAP pathway induces primary ovarian insufficiency

Wang

Liu

et al. 2022

Nat Commun

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“…High level of FAS in antral follicle initiated ovarian cell death [ 24 ]. RIPK1 , FADD , TRADD and TNFRSF1A were all highly expressed in cell apoptosis [ 25 ], which would also promote cell apoptosis in the ovary. In this study, 23, 8, 4, 2, 6, 16 differential lncRNAs targeted CTSS , FAS , RIPK1 , FADD , TRADD , and TNFRSF1A (Supplementary Table S 8 –1), respectively, which were significantly enriched in the apoptosis pathway, indicating that the above differential lncRNAs might inhibit ovarian development of Yili geese.…”

Section: Discussionmentioning

confidence: 99%

Comprehensive analysis of differentially expressed profiles of mRNA, lncRNA, and miRNA of Yili geese ovary at different egg-laying stages

Zhao

et al. 2022

BMC Genomics

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Background The development of the ovaries is an important factor that affects egg production performance in geese. Ovarian development is regulated by genes that are expressed dynamically and stage-specifically. The transcriptome profile analysis on ovarian tissues of goose at different egg laying stages could provide an important basis for screening and identifying key genes regulating ovarian development. Results In this study, 4 ovary tissues at each breeding period of pre-laying (PP), laying (LP), and ceased-laying period (CP), respectively, with significant morphology difference, were used for RNA extraction and mRNAs, lncRNAs, and miRNAs comparison in Yili geese. CeRNA regulatory network was constructed for key genes screening. A total of 337, 1136, and 525 differentially expressed DE mRNAs, 466, 925, and 742 DE lncRNAs and 258, 1131 and 909 DE miRNAs were identified between PP and LP, between CP and LP, and between CP and PP groups, respectively. Functional enrichment analysis showed that the differentially expressed mRNAs and non-coding RNA target genes were mainly involved in the cell process, cytokine-cytokine receptor interaction, phagosome, calcium signaling pathway, steroid biosynthesis and ECM-receptor interaction. Differential genes and non-coding RNAs, PDGFRB, ERBB4, LHCGR, MSTRG.129094.34, MSTRG.3524.1 and gga-miR-145–5p, related to reproduction and ovarian development were highly enriched. Furthermore, lncRNA-miRNA-mRNA regulatory networks related to ovary development were constructed. Conclusions Our study found dramatic transcriptomic differences in ovaries of Yili geese at different egg-laying stages, and a differential lncRNA-miRNA-mRNA regulatory network related to cell proliferation, differentiation and apoptosis and involved in stromal follicle development were established and preliminarily validated, which could be regarded as a key regulatory pathway of ovarian development in Yili geese.

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“…Researchers confirmed the ability of AChE to regulate MLKL phosphorylation (seemingly through RIPK1) by using a three-dimensional in vitro culture of macaque follicles, but no associations between necroptotic proteins and follicle degradation were detected [ 208 ]. The RIPK1 and RIPK3 genes are overexpressed in atretic bovine follicles, and a system biology approach suggested that necroptosis may be actively involved in atresia [ 209 ]. SIRT1 promotes granulosa cell death and regulates RIPK1 and MLKL phosphorylation; however, the mechanism behind cell death is RIPK1-dependent apoptosis rather than MLKL-dependent necroptosis because it is accompanied by caspase-3 processing and PARP cleavage [ 210 ].…”

Section: Regulation Of Pcd During Follicular Atresiamentioning

confidence: 99%

A matter of new life and cell death: programmed cell death in the mammalian ovary

Chesnokov,

Mamedova,

Zhivotovsky

et al. 2024

J Biomed Sci

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Background The mammalian ovary is a unique organ that displays a distinctive feature of cyclic changes throughout the entire reproductive period. The estrous/menstrual cycles are associated with drastic functional and morphological rearrangements of ovarian tissue, including follicular development and degeneration, and the formation and subsequent atrophy of the corpus luteum. The flawless execution of these reiterative processes is impossible without the involvement of programmed cell death (PCD). Main text PCD is crucial for efficient and careful clearance of excessive, depleted, or obsolete ovarian structures for ovarian cycling. Moreover, PCD facilitates selection of high-quality oocytes and formation of the ovarian reserve during embryonic and juvenile development. Disruption of PCD regulation can heavily impact the ovarian functions and is associated with various pathologies, from a moderate decrease in fertility to severe hormonal disturbance, complete loss of reproductive function, and tumorigenesis. This comprehensive review aims to provide updated information on the role of PCD in various processes occurring in normal and pathologic ovaries. Three major events of PCD in the ovary—progenitor germ cell depletion, follicular atresia, and corpus luteum degradation—are described, alongside the detailed information on molecular regulation of these processes, highlighting the contribution of apoptosis, autophagy, necroptosis, and ferroptosis. Ultimately, the current knowledge of PCD aberrations associated with pathologies, such as polycystic ovarian syndrome, premature ovarian insufficiency, and tumors of ovarian origin, is outlined. Conclusion PCD is an essential element in ovarian development, functions and pathologies. A thorough understanding of molecular mechanisms regulating PCD events is required for future advances in the diagnosis and management of various disorders of the ovary and the female reproductive system in general.

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Death Processes in Bovine Theca and Granulosa Cells Modelled and Analysed Using a Systems Biology Approach

Cited by 8 publications

References 56 publications

BNC1 deficiency-triggered ferroptosis through the NF2-YAP pathway induces primary ovarian insufficiency

BNC1 deficiency-triggered ferroptosis through the NF2-YAP pathway induces primary ovarian insufficiency

Comprehensive analysis of differentially expressed profiles of mRNA, lncRNA, and miRNA of Yili geese ovary at different egg-laying stages

A matter of new life and cell death: programmed cell death in the mammalian ovary

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