The relationship between the mTOR signaling pathway and ovarian aging in peak-phase and late-phase laying hens

Hao, Erying; Wang, Dehe; Chen, Yifan; Zhou, Rongyan; Chen, Hui; Huang, Ren-lu

doi:10.1016/j.psj.2020.10.005

Cited by 32 publications

(30 citation statements)

References 49 publications

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“…2 ). Although the observed changes in levels were small (1.5-fold or less) in these situations, the magnitudes of these changes were consistent with those reported in previous studies [ 34 , 35 ]. In contrast, we found that treatment with MHY1485 alone (under non-irradiation conditions) provided limited increase in the levels of p-mTOR and downstream targets in CT26 and LLC ( Fig.…”

Section: Discussionsupporting

confidence: 92%

MHY1485 enhances X-irradiation-induced apoptosis and senescence in tumor cells

Sun

Morikawa

Sogo

et al. 2021

Journal of Radiation Research

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The mammalian target of rapamycin (mTOR) is a sensor of nutrient status and plays an important role in cell growth and metabolism. Although inhibition of mTOR signaling promotes tumor cell death and several mTOR inhibitors have been used clinically, recent reports have shown that co-treatment with MHY1485, an mTOR activator, enhances the anti-cancer effects of anti-PD-1 antibody and 5-fluorouracil. However, it remains unclear whether MHY1485 treatment alters the effects of radiation on tumor cells. In this study, the radiosensitizing effects of MHY1485 were investigated using murine CT26 and LLC cell lines. We examined mTOR signaling, tumor cell growth, colony formation, apoptosis, senescence, oxidative stress, p21 accumulation and endoplasmic reticulum (ER) stress levels in cells treated with MHY1485 and radiation, either alone or together. We found that MHY1485 treatment inhibited growth and colony formation in both cell lines under irradiation and no-irradiation conditions, results that were not fully consistent with MHY1485’s known role in activating mTOR signaling. Furthermore, we found that combined treatment with MHY1485 and radiation significantly increased apoptosis and senescence in tumor cells in association with oxidative stress, ER stress and p21 stabilization, compared to radiation treatment alone. Our results suggested that MHY1485 enhances the radiosensitivity of tumor cells by a mechanism that may differ from MHY1485’s role in mTOR activation.

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Section: Discussionsupporting

confidence: 92%

MHY1485 enhances X-irradiation-induced apoptosis and senescence in tumor cells

Sun

Morikawa

Sogo

et al. 2021

Journal of Radiation Research

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“…In laying hens, productive performance and egg quality are strictly linked to ovarian performance. One of the most dominant factors that cause ovarian damage is oxidative stress which positively correlates with high productivity and the aging process ( Finkel and Holbrook, 2000 ; Hao et al, 2021 ). Dysfunction and aging of the ovaries can lead to detrimental effects for poultry performance, reproductive activity, hatching rate, product quality and life span.…”

Section: Discussionmentioning

confidence: 99%

Dietary phytogenic inclusion level affects production performance and expression of ovarian cytoprotective genes in laying hens

Brouklogiannis¹,

Anagnostopoulos²,

Griela³

et al. 2023

Poultry Science

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“…Previous research indicated that differentially expressed genes (DEGs) were associated with high rates of egg production in the chicken hypothalamic–pituitary–ovarian axis via the transcriptome and identified DEGs that regulate the mTOR signaling pathway, the Jak-STAT signaling pathway, tryptophan metabolism, and the PI3K-Akt signaling pathways in the HPO axis in laying hens [ 71 ]. In vitro, chicken granulosa cells treated with the mTOR agonist MHY1485 (mTOR activator) showed significantly enhanced granulosa cell proliferation, inhibited apoptosis, and significantly increased mTOR-signaling-related gene (ribosomal protein S6 kinase (S6K) , eIF4E binding protein 1 (4E-BP1) , and protein kinase C (PKC)) expression in the peak phase (30-week-old) and late phase (70-week-old) laying hens [ 72 ]. Recent evidence also suggests that the mTOR signaling pathway plays important roles in folliculogenesis [ 73 ], ovarian cell proliferation, steroidogenesis [ 74 ], and oocyte maturation [ 75 ].…”

Section: Discussionmentioning

confidence: 99%

Untargeted Metabolomics Revealed Potential Biomarkers of Small Yellow Follicles of Chickens during Sexual Maturation

et al. 2023

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Sexual maturation provides economically important traits in poultry production. Research on the initiation mechanism of sexual maturity is of great significance for breeding high-yield laying hens. However, the underlying mechanisms are not fully clear. Here, one hundred and fifty Chahua No. 2 laying hens (the CH2 group, which has precocious puberty) and one hundred and fifty Wu Liang Shan black-bone laying hens (the WLS group, a late-maturing chicken breed) with similar weights and ages were randomly selected. ELISA was used to determine the secretion levels of luteinizing hormone (LH), estradiol (E2), and progesterone (P4) in 150-day-old serum and small yellow follicle (SYF) tissues. A histology examination, immunohistochemistry, and quantitative real-time PCR (qPCR) were used to explore the molecular mechanism of how some genes related to oxidative stress affect sexual maturation. The results showed that the secretion levels of LH, E2, and P4 in the CH2 group serum and SYF were higher than those in the WLS group. The results of the real-time PCR of all genes showed that the expression levels of cytochrome P450 family 11 subfamily A member 1, steroidogenic acute regulatory protein, follicle-stimulating hormone receptor, and cytochrome P450 family 19 subfamily A member 1 in the CH2 group were significantly higher than those in the WLS groups (p < 0.001). Untargeted metabolomics combined with multivariate statistical analysis was used to identify biomarkers of SYF tissues in the CH2 and WLS groups. A trajectory analysis of the principal component analysis (PCA) results showed that the samples within the group were clustered and that the samples were dispersed between the CH2 and the WLS groups, indicating that the results of the measured data were reliable and could be used for further research. Further analysis showed that a total of 319 metabolites in small yellow follicles of the CH2 and WLS groups were identified, among which 54 downregulated differential metabolites were identified. These 54 metabolites were found as potential CH2 biomarkers compared with WLS at 150 days, and the different expressions of L-arginine, L-prolinamide, (R)-4-hydroxymandelate, glutathione, and homovanillic acid were more significant. Twenty metabolic pathways were found when significantly differential metabolites were queried in the KEGG database. According to the impact values of the metabolic pathways, eighteen differential metabolites belonged to the mTOR signaling pathway, glutathione metabolism, ABC transporters, the cell ferroptosis pathway, and D-arginine and D-ornithine metabolism. Interestingly, we identified that the cell ferroptosis pathway played an important role in chicken follicle selection for the first time. The histology and immunohistochemistry of SYF showed that the number of granulosa cells increased in the CH2 groups and the expression levels of glutathione peroxidase 4, tumor protein p53, ribosomal protein S6 kinase, and sterol regulatory element binding protein 1 in the granulosa cell layer were upregulated in the CH2 group at the time of sexual maturation. Furthermore, we also speculated that the antioxidant system may play an indispensable role in regulating sexual maturity in chickens. Overall, our findings suggest differentially expressed metabolites and metabolic pathways between CH2 and WLS chickens, providing new insights into the initiation mechanism of sexual maturation.

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The relationship between the mTOR signaling pathway and ovarian aging in peak-phase and late-phase laying hens

Cited by 32 publications

References 49 publications

MHY1485 enhances X-irradiation-induced apoptosis and senescence in tumor cells

MHY1485 enhances X-irradiation-induced apoptosis and senescence in tumor cells

Dietary phytogenic inclusion level affects production performance and expression of ovarian cytoprotective genes in laying hens

Untargeted Metabolomics Revealed Potential Biomarkers of Small Yellow Follicles of Chickens during Sexual Maturation

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