Moderate Aerobic Exercise Regulates Follicular Dysfunction by Initiating Brain-Derived Neurotrophic Factor (BDNF)-Mediated Anti-Apoptotic Signaling Pathways in Polycystic Ovary Syndrome

Zhang, Yaling; Chen, Dejian; Wang, Daojuan; Wang, Lei; Weng, Yajing; Wang, Hongwei; Wu, Xiaoke; Wang, Yong

doi:10.3390/jcm11195584

Cited by 4 publications

(1 citation statement)

References 54 publications

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“…TrkA receptors mainly activate phosphatidylinositol-3 kinase (PI3K) and mitotic-activated protein kinase (MAPK) to promote cells' survival and proliferation [27]. In previous studies, neurotrophic factors and their receptors have been shown to play facilitative roles in ovarian development, oocyte maturation, and blastocyst formation in animals [28][29][30][31][32][33]. PI3K/AKT signaling is an important pathway that affects mammalian reproduction.…”

Section: Introductionmentioning

confidence: 99%

NTRK2 Promotes Sheep Granulosa Cells Proliferation and Reproductive Hormone Secretion and Activates the PI3K/AKT Pathway

Jia,

Liu,

Wang

et al. 2024

Animals

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Neurotrophin receptor B (NTRK2), also named TRKB, belongs to the neurotrophic factor family. Previous studies have shown that NTRK2 is associated with high fertility in mammals. However, the molecular mechanism and regulatory pathway of this neurotrophic factor remain unclear. In this study, NTRK2 overexpression and NTRK2-siRNA were constructed to detect the effects of NTRK2 on the proliferation and hormone secretion of the ovarian granulosa cells (GCs) of sheep. We successfully isolated follicular phase granulosa cells in vitro from the ovaries of sheep in simultaneous estrus, and the immunofluorescence results confirmed that NTRK2 was expressed in the collected cells. Subsequently, the effect of NTRK2 on the proliferation of sheep granulosa cells was examined via cell transfection experiments. The results showed that the expression of CDK4 and CyclinD2 was significantly increased after NTRK2 overexpression, while the opposite trend was observed after the inhibition of NTRK2 expression (p < 0.05). The EdU and CCK-8 assays showed that the proliferation rate of sheep GCs was significantly increased after NTRK2 overexpression, while the opposite trend was observed after the inhibition of NTRK2 expression (p < 0.05). Moreover, NTRK2 significantly increased the expression of steroidogenesis-related genes, including steroidogenic acute regulatory protein (STAR) and hydroxy-δ-5-steroid dehydrogenase (HSD3B1), and cytochrome P450 family 19 subfamily A member 1 (CYP19A1). The ELISA results showed that the secretion levels of E2 and P4 significantly increased after NTRK2 overexpression, while the opposite trend was observed after the inhibition of NTRK2 expression (p < 0.05). Previous studies had confirmed that NTRK2 gene belongs to the PI3K-AKT signaling pathway and participates in the signaling of this pathway. This was demonstrated by protein‒protein interaction analysis and NTRK2 belongs to the PI3K-AKT pathway. The modification of PI3K and AKT, markers of the PI3K-AKT pathway, via phosphorylation was increased after NTRK2 overexpression in the sheep GCs, while the opposite trend was observed after the inhibition of NTRK2 expression (p < 0.05). Overall, these results suggest that the NTRK2 gene regulates the proliferation of GCs and the secretion of steroid hormones in sheep, and that it influences the phosphorylation level of the PI3K/AKT signaling pathway. These findings provided a theoretical basis and new perspectives for exploring the regulation of NTRK2 gene in the development of ovine follicles.

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Section: Introductionmentioning

confidence: 99%

NTRK2 Promotes Sheep Granulosa Cells Proliferation and Reproductive Hormone Secretion and Activates the PI3K/AKT Pathway

Jia,

Liu,

Wang

et al. 2024

Animals

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Screening and identification of key biomarkers associated with endometriosis using bioinformatics and next generation sequencing data analysis

Vastrad,

Vastrad

2024

Preprint

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Endometriosis is a common cause of endometrial-type mucosa outside the uterine cavity with symptoms such as painful periods, chronic pelvic pain, pain with intercourse and infertility. However, the early diagnosis of endometriosis is still restricted. The purpose of this investigation is to identify and validate the key biomarkers of endometriosis. Next generation sequencing (NGS) dataset GSE243039 was obtained from the Gene Expression Omnibus (GEO) database, and differentially expressed genes (DEGs) between endometriosis and normal control samples were identified. After screening of DEGs, gene ontology (GO) and REACTOME pathway enrichment analyses were performed. Furthermore, a protein-protein interaction (PPI) network was constructed and modules were analysed using the Human Integrated Protein-Protein Interaction rEference (HIPIE) database and Cytoscape software, and hub genes were identified. Subsequantely, a network between miRNAs and hub genes, and network between TFss and hub genes were constructed using the miRNet and NetworkAnalyst tool, and possible key miRNAs and TFs were predicted. Finally, receiver operating characteristic curve (ROC) analysis was used to validate the hub genes. A total of 958 DEGs, including 479 up regulated genes and 479 down regulated genes, were screened between endometriosis and normal control samples. GO and REACTOME pathway enrichment analyses of the 958 DEGs showed that they were mainly involved in multicellular organismal process, developmental process, signaling by GPCR and muscle contraction. Further analysis of the PPI network and modules identified 10 hub genes, including VCAM1, SNCA, PRKCB, ADRB2, FOXQ1, MDFI, ACTBL2, PRKD1, DAPK1 and ACTC1. Possible target miRNAs, including hsa-mir-3143 and hsa-mir-2110, and target TFs, including TCF3 and CLOCK, were predicted by constructing a miRNA-hub gene regulatory network and TF-hub gene regulatory network. This investigation used bioinformatics techniques to explore the potential and novel biomarkers. These biomarkers might provide new ideas and methods for the early diagnosis, treatment, and monitoring of endometriosis.

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The effect of calorie-restriction along with thylakoid membranes of spinach on the gut-brain Axis Pathway and oxidative stress biomarkers in obese women with polycystic ovary syndrome: a Randomized, Double-blind, placebo-controlled clinical trial

Nikrad,

Farhangi,

Fard Tabrizi

et al. 2023

J Ovarian Res

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Background Women with polycystic ovary syndrome (PCOS) have higher intestinal mucosal permeability, leading to the lipopolysaccharide (LPS) leakage and endotoxemia. This, in turn, leads to oxidative stress (OS) and neuro-inflammation caused by the gut-brain axis, affecting the neurotrophic factors levels such as brain-derived neurotrophic factor (BDNF) and S100 calcium-binding protein B (S100 B) levels. In this study, it was hypothesized that the thylakoid membranes of spinach supplementation along with a hypocaloric diet may have improved the LPS levels, neurotrophic factors, and OS in PCOS patients. Methods In this double-blind, randomized, placebo-controlled, and clinical trial, 48 women with obesity and diagnosed with PCOS based on Rotterdam criteria were randomly assigned to thylakoid (N = 21) and placebo groups (N = 23). A personalized hypocaloric diet with 500 calories less than the total energy expenditure was prescribed to all patients. The participants were daily supplemented with either a 5 g/day thylakoid-rich spinach extract or a placebo (5 g cornstarch) for 12 weeks along with a prescribed low-calorie diet. Anthropometric measurements and biochemical parameters were assessed at baseline and after the 12-week intervention. Results A statistically significant decrease in the LPS levels (P < 0.001) and an increase in the BDNF levels (P < 0.001) were recorded for the participants receiving the oral thylakoid supplements and a low-calorie diet. Furthermore, significant decreases were observed in fasting blood glucose, insulin, homeostatic model of assessment for insulin resistance, free testosterone index, and follicle-stimulating hormone / luteinizing hormone ratio in both groups (P < 0.05). No significant differences were detected between the two groups regarding the changes in malondialdehyde, catalase, total antioxidant capacity, and S100B levels (P > 0.05). Conclusions In sum, the thylakoid membranes of spinach supplemented with a hypocaloric diet reduced the LPS levels, increased the BDNF levels, and improved the glycemic profile and sex-hormone levels; however, they had no effects on the OS markers levels after 12 weeks of intervention.

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Moderate Aerobic Exercise Regulates Follicular Dysfunction by Initiating Brain-Derived Neurotrophic Factor (BDNF)-Mediated Anti-Apoptotic Signaling Pathways in Polycystic Ovary Syndrome

Cited by 4 publications

References 54 publications

NTRK2 Promotes Sheep Granulosa Cells Proliferation and Reproductive Hormone Secretion and Activates the PI3K/AKT Pathway

NTRK2 Promotes Sheep Granulosa Cells Proliferation and Reproductive Hormone Secretion and Activates the PI3K/AKT Pathway

Screening and identification of key biomarkers associated with endometriosis using bioinformatics and next generation sequencing data analysis

The effect of calorie-restriction along with thylakoid membranes of spinach on the gut-brain Axis Pathway and oxidative stress biomarkers in obese women with polycystic ovary syndrome: a Randomized, Double-blind, placebo-controlled clinical trial

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