title: Tripterygiumglycosides induce premature ovarian failure in rats by promoting p53 phosphorylation and activating the serine/threonine kinase 11-p53-p21 signaling pathway.
abstract: Premature ovarian failure (POF) is a typical pathological disease of the reproductive system in aging females. Infection, inflammation, immune abnormalities, genetic mutation, radiotherapy and chemotherapy can cause POF.Tripterygiumglycosides (TGs) are a component extracted from the Chinese herbTripterygium wilfordiiHook. f., also known as Huangteng. Although TGs have been used to treat various diseases, drug resistance and toxicity can affect patients. The aim of the present study was to investigate the mechanism of TG-induced POF in rats. The rats were treated with different concentrations of TG, and pathology assays showed that the TG-induced POF was predominantly composed of interstitial cells in a fibrous matrix with a reduced number of follicles at each stage and an increased number of collapsed oocytes. Furthermore, reverse transcription-quantitative polymerase chain reaction (PCR) and immunohistochemistry assays indicated that the expression levels of serine/threonine kinase 11 (Stk11), p53 p21 and activated caspase-3 were elevated significantly in the TG-treated groups. Serine 15 phosphorylation of p53 was also enhanced significantly in the TG-treated groups. In addition, a chromatin immunoprecipitation-PCR assay revealed that the TGs induced p53 activation and enhanced the transcription of p21. In conclusion, TGs induce apoptosis and necrosis in rat ovarian tissues, as well as POF, via p53 phosphorylation and activation of the Stk11-p53-p21 signaling pathway.
authors.affiliation: Department of Gynecology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200031, P.R. China ; Shanghai Geriatric Institute of Chinese Medicine, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200031, P.R. China.
authors.forename: T E
authors.initials: TE
authors.lastname: Liu
authors.affiliation: Department of Gynecology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200031, P.R. China.
authors.forename: Lina
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Gynecology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200031, P.R. China.
authors.forename: Suwei
authors.initials: S
authors.lastname: Wang
authors.affiliation: Shanghai Geriatric Institute of Chinese Medicine, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200031, P.R. China.
authors.forename: Chuan
authors.initials: C
authors.lastname: Chen
authors.affiliation: Department of Gynecology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200031, P.R. China.
authors.forename: Jin
authors.initials: J
authors.lastname: Zheng
keywords: Stk11-p53-p21 signaling pathway; Tripterygium glycosides; p53 phosphorylation; premature ovarian failure