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1.
Sheng Li Xue Bao ; 74(3): 370-380, 2022 Jun 25.
Artigo em Chinês | MEDLINE | ID: mdl-35770635

RESUMO

Polycystic ovary syndrome (PCOS) is a common disease caused by complex endocrine and metabolic abnormalities in women of childbearing age. Metformin is the most widely used oral hypoglycemic drug in clinic. In recent years, metformin has been used in the treatment of PCOS, but its mechanism is not clear. In this study, we aimed to investigate the effect of metformin on PCOS and its mechanism through PCOS mouse model. Female C57BL/6J mice aged 4-5 weeks were intragastrically given letrozole (1 mg/kg daily) combined with a high-fat diet (HFD) for 21 days to establish the PCOS model. After modeling, metformin (200 mg/kg daily) was intragastrically administered. One month later, the body weight and oral glucose tolerance test (OGTT) were measured. Hematoxylin eosin (H&E) staining was used to detect the pathological changes of ovary. The serum levels of anti-Mullerian hormone (AMH), follicle-stimulating hormone (FSH), luteinizing hormone (LH), E2 and testosterone (T) were measured by ELISA. The expression of DDX4/MVH was detected by immunohistochemistry. DDX4/MVH and PCNA were co-labeled by immunofluorescence. The protein levels of DDX4/MVH, PCNA, cyclin D2, AMPK and mTOR were detected by Western blot. The results showed that after metformin treatment, the body weights of PCOS mice were gradually returned to normal, glucose tolerance was significantly improved, serum E2 levels were increased, while AMH, LH, T levels and LH/FSH ratio were decreased. Ovarian polycystic lesions were reduced with reduced atresia follicles. Furthermore, the number of proliferative female germline stem cells (FGSCs) and levels of proliferation related proteins (PCNA, cyclin D2) were significantly increased, and the p-mTOR and p-AMPK levels were markedly up-regulated. These results suggest that metformin treatment not only improves hyperandrogenemia, glucose intolerance and polycystic ovarian lesions in PCOS, but also activates the function of FGSCs. The underlying mechanism may be related to the phosphorylation of AMPK and mTOR. These findings provide new evidence to use metformin in the treatment of PCOS and follicular development disorder.


Assuntos
Metformina , Células-Tronco de Oogônios , Cistos Ovarianos , Neoplasias Ovarianas , Síndrome do Ovário Policístico , Proteínas Quinases Ativadas por AMP , Animais , Ciclina D2 , Feminino , Hormônio Foliculoestimulante/uso terapêutico , Humanos , Hormônio Luteinizante/uso terapêutico , Metformina/farmacologia , Camundongos , Camundongos Endogâmicos C57BL , Células-Tronco de Oogônios/metabolismo , Cistos Ovarianos/tratamento farmacológico , Síndrome do Ovário Policístico/tratamento farmacológico , Antígeno Nuclear de Célula em Proliferação/uso terapêutico , Serina-Treonina Quinases TOR
2.
Pharm Biol ; 59(1): 1314-1325, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34569428

RESUMO

CONTEXT: Lycium barbarum L. (Solanaceae) seed oil (LBSO) exerts LBSO exerts protective effects in the testis in vivo and in vitro via upregulating SIRT3. OBJECTIVE: This study evaluates the effects and mechanism of LBSO in the d-galactose (d-gal)-induced ageing testis. MATERIALS AND METHODS: Male Sprague Dawley (SD) rats (n = 30, 8-week-old) were randomly divided into three groups: LBSO group (n = 10) where rats received subcutaneous injection of d-gal at 125 mg/kg/day for 8 weeks and intragastric administration of LBSO at 1000 mg/kg/day for 4 weeks, ageing model group (n = 10) received 8-week-sunbcutaneous injection of d-gal, and control group (n = 10) with same administration of normal saline. Lentivirus had established TM4 cells with SIRT3 overexpression or silencing before LBSO intervened in vitro. RESULTS: Treatment with LBSO, the levels of INHB and testosterone both increased, compared to ageing model. In vitro, we found the ED50 of LBSO was 86.72 ± 1.49 and when the concentration of LBSO at 100 µg/mL to intervene TM4 cells, the number of cells increased from 8120 ± 676.2 to 15251 ± 1119, and the expression of SIRT3, HO-1, and SOD upregulated. However, HO-1 and SOD were dysregulated by silencing SIRT3. On the other hand, the expression of AMPK and PGC-1α upregulated as an effect of SIRT3 overexpression by lentivirus, meanwhile the same increasing trend of that being found in cells treated with LBSO, compared to control group. DISCUSSION AND CONCLUSIONS: LBSO alleviated oxidative stress in d-gal-induced sub-acutely ageing testis and TM4 cells by suppressing the oxidative stress to mitochondria via SIRT3/AMPK/PGC-1α.


Assuntos
Lycium/química , Estresse Oxidativo/efeitos dos fármacos , Óleos de Plantas/farmacologia , Testículo/efeitos dos fármacos , Quinases Proteína-Quinases Ativadas por AMP/genética , Envelhecimento/efeitos dos fármacos , Animais , Linhagem Celular , Masculino , Camundongos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/patologia , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/genética , Óleos de Plantas/isolamento & purificação , Ratos , Ratos Sprague-Dawley , Sementes , Células de Sertoli/efeitos dos fármacos , Células de Sertoli/patologia , Sirtuínas/genética , Testículo/patologia
3.
Zhonghua Nan Ke Xue ; 22(1): 6-11, 2016 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-26931018

RESUMO

OBJECTIVE: To investigate the effects of single heat stress treatment on spermatogenic cells in mice. METHODS: We randomly divided 36 C57 male mice into a control and a heat stress treatment group and submerged the lower part of the torso in water at 25 °C and 43 °C, respectively, both for 15 minutes. At 1, 7, and 14 days after treatment, we obtained the testicular organ indexes, observed the changes in testicular morphology by HE staining, and determined the location and expression levels of the promyelocytic leukemia zinc finger (PLZF) and synaptonemal comlex protein-3 (SCP-3) in the testis tissue by immunohistochemistry and Western blot. RESULTS: The testicular organ index was significantly lower in the heat stress treatment than in the control group (P < 0.05). Compared with the controls, the heat shock-treated mice showed loosely arranged spermatogenic cells scattered in the seminiferous tubules at 1 day after heat stress treatment, atrophied, loosely arranged and obviously reduced number of spermatogenic cells at 7 days, and relatively closely arranged seminiferous tubules and increased number and layers of spermatogenic cells at 14 days. The number of SCP-3 labelled spermatocytes obviously decreased in the heat stress-treated animals at 1 and 7 days and began to increase at 14 days. The PLZF protein expression was significantly reduced in the heat stress treatment group at 1 day as compared with that in the control (0.19 ± 0.12 vs 0.64 ± 0.03, P < 0.01), but elevated to 0.77 ± 0.02 at 7 and 14 days, even remarkably higher than in the control animals (P < 0.01). CONCLUSION: Heat stress treatment can induce short-term dyszoospermia in mice, which can be recovered with the prolonged time after treatment.


Assuntos
Temperatura Alta , Proteínas Nucleares/metabolismo , Espermatócitos/patologia , Testículo/metabolismo , Fatores de Transcrição/metabolismo , Proteínas Supressoras de Tumor/metabolismo , Animais , Western Blotting , Proteínas de Ciclo Celular , Proteínas de Ligação a DNA , Imuno-Histoquímica , Masculino , Camundongos , Proteína da Leucemia Promielocítica , Túbulos Seminíferos/citologia , Espermatócitos/citologia
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