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Tong Sun, Wen-Bo Deng, Hong-Lu Diao, Hua Ni, Yu-Yan Bai, Xing-Hong Ma, Li-Bin Xu, and Zeng-Ming Yang

Prostaglandin (PGE) 2 is the most common prostanoid and plays an important role in female reproduction. The aim of this study was to examine the expression and regulation of microsomal (m) PGE synthase (PGES)-1 and cytosolic (c) PGES in the mouse ovary during sexual maturation, gonadotropin treatment and luteal development by in situ hybridization and immunohistochemistry. Both mPGES-1 mRNA signals and immunostaining were localized in the granulosa cells, but not in the thecal cells and oocytes. cPGES mRNA signals were localized in both granulosa cells and oocytes, whereas cPGES immunostaining was exclusively localized in the oocytes. In our superovulated model of immature mice, there was a basal level of mPGES-1 mRNA signals in the granulosa cells at 48 h after equine chorionic gonadotropin (eCG) treatment. mPGES-1 mRNA level was induced by human chorionic gonadotropin (hCG) treatment for 0.5 h, whereas mPGES-1 immunostaining was slightly induced at 0.5 h after hCG treatment and reached a maximal level at 3 h after hCG treatment. eCG treatment had no obvious effects on either cPGES mRNA signals or immunostaining. A strong level of cPGES immunostaining was present in both unstimulated and eCG-treated groups. Both mPGES-1 mRNA signals and immunostaining were highly detected in the corpus luteum 2 days post-hCG injection and declined from days 3 to 7 post-hCG injection. cPGES immunostaining was at a basal level or not detectable from days 1 to 7 after hCG injection and was highly expressed in the corpus luteum from days 9 to 15 post-hCG injection. PGE2 biosynthesized through the mPGES-1 pathway may be important for follicular development, ovulation and luteal formation.

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Qiaoli Cui, Yijing Liao, Yaojing Jiang, Xiaohang Huang, Weihong Tao, Quanquan Zhou, Anna Shao, Ying Zhao, Jia Li, Anran Ma, Zhihong Wang, Li Zhang, Zunyuan Yang, Yinan Liang, Minglin Wu, Zhenyan Yang, Wen Zeng, and Qinghua Wang

Glucagon-like peptide 1 (GLP-1) is an insulinotropic hormone and plays an important role in regulating glucose homeostasis. GLP-1 has a short half-life (t1/2<2 min) due to degrading enzyme dipeptidyl peptidase-IV and rapid kidney clearance, which limits its clinical application as a therapeutic reagent. We demonstrated recently that supaglutide, a novel GLP-1 mimetic generated by recombinant fusion protein techniques, exerted hypoglycemic and beta cell trophic effects in type 2 diabetes db/db mice. In the present study, we examined supaglutide’s therapeutic efficacy and pharmacokinetics in diabetic rhesus monkeys. We found that a single subcutaneous injection of supaglutide of tested doses transiently and significantly reduced blood glucose levels in a dose-dependent fashion in the diabetic monkeys. During a 4-weeks intervention period, treatment of supaglutide of weekly dosing dose-dependently decreased fasting and random blood glucose levels. This was associated with significantly declined plasma fructosamine levels. The repeated administration of supaglutide remarkably also decreased body weight in a dose-dependent fashion accompanied by decreased food intake. Intravenous glucose tolerance test results showed that supaglutide improved glucose tolerance. The intervention also showed enhanced glucose-stimulated insulin secretion and improved lipid profile in diabetic rhesus monkeys. These results reveal that supaglutide exerts beneficial effects in regulating blood glucose and lipid homeostasis in diabetic rhesus monkeys.

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Lei Du, Yang Wang, Cong-Rong Li, Liang-Jian Chen, Jin-Yang Cai, Zheng-Rong Xia, Wen-Tao Zeng, Zi-Bin Wang, Xi-Chen Chen, Fan Hu, Dong Zhang, Xiao-Wei Xing, and Zhi-Xia Yang

Polycystic ovarian syndrome (PCOS) is a major severe ovary disorder affecting 5–10% of reproductive women around the world. PCOS can be considered a metabolic disease because it is often accompanied by obesity and diabetes. Brown adipose tissue (BAT) contains abundant mitochondria and adipokines and has been proven to be effective for treating various metabolic diseases. Recently, allotransplanted BAT successfully recovered the ovarian function of PCOS rat. However, BAT allotransplantation could not be applied to human PCOS; the most potent BAT is from infants, so voluntary donors are almost inaccessible. We recently reported that single BAT xenotransplantation significantly prolonged the fertility of aging mice and did not cause obvious immunorejection. However, PCOS individuals have distinct physiologies from aging mice; thus, it remains essential to study whether xenotransplanted rat BAT can be used for treating PCOS mice. In this study, rat-to-mouse BAT xenotransplantation fortunately did not cause severe rejection reaction, and significantly recovered ovarian functions, indicated by the recovery of fertility, oocyte quality, and the levels of multiple essential genes and kinases. Besides, the blood biochemical index, glucose resistance, and insulin resistance were improved. Moreover, transcriptome analysis showed that the recovered PCOS F0 mother following BAT xenotransplantation could also benefit the F1 generation. Finally, BAT xenotransplantation corrected characteristic gene expression abnormalities found in the ovaries of human PCOS patients. These findings suggest that BAT xenotransplantation could be a novel therapeutic strategy for treating PCOS patients.