TOB1 modulates the decidualization of human endometrial stromal cells via the Notch pathway.

BACKGROUND: Decidualization is critical for embryo implantation and the success of pregnancy; however, the mechanisms underlying this process remain largely unknown. MATERIALS AND METHODS: In the present study, RNA sequencing was used to detect the expression levels of transducer of ERBB2/1(TOB1) in endometrial samples derived from proliferative and secretory phases. A decidualization model was induced using the combination of estrogen (E2) and progestin (P4) in human endometrial stromal cells (HESCs). The cell counting kit-8 assay was used to detect the viability of HESCs. Related proteins were detected by qPCR and western blot. RESULT: The results indicated that TOB1 expression was upregulated in the secretory endometrial samples compared with the corresponding expression observed in the proliferative samples. The expression levels of TOB1 and Notch1 were markedly increased in E2P4-treated HESCs compared with those in the control cells. Treatment with E2P4 strongly suppressed the proliferation of HESCs and induced a G1-phase cell cycle arrest. These effects were abolished by knockdown of TOB1 or treatment with of the cells with the Notch inhibitor N-[N-(3,5-difluorophenacetyl)-1-alanyl]-S-phenylglycine t-butyl ester. CONCLUSIONS: Therefore, these findings highlighted an important role for TOB1/Notch signaling in E2P4-induced decidualization in HESCs, which may provide novel targets for improving the endometrial receptivity.

[Study on the relationship between altered expression of annexin A4 and endometrial receptivity during the implantation window in infertile patients with endometriosis].

OBJECTIVE: To identify the differential expressed proteins, and to investigate the relationship between altered expression of annexin A4 during window of implantation [WOI (at day-6 after ovulatory day)] in infertile patients with endometriosis and endometrial receptivity. METHODS: Two-dimensional fluorescence differential in-gel electrophoresis (2D-DIGE) and matrix-assist laser desorption ionization-time of flight-mass spectrometry (MALDI-TOF-MS) were used to detect protein expression in endometrial WOI in 10 infertile cases with endometriosis as endometriosis group and 10 infertile cases with tubal factors as control group. The semi-quantitative validation of annexin A4 in the eutopic endometrial tissue during WOI was analyzed by western blot. RESULTS: By comparing protein profiles, there were 7 meaningful differential proteins during WOI in infertile patients with endometriosis. One protein with an isoelectric point of 5.84 and relative molecular weight of 36 100 were down regulated 348% in samples of endometriosis group. It was identified as annexin A4 by mass spectrometry. By western blot, relative intensity of annexin A4 in endometriosis group was 7.2 ± 0.9, which was lower than 17.8 ± 2.6 in control group significantly (t = 7.654, P = 0.002). CONCLUSION: Lower expression of annexin A4 during WOI in infertile patients with endometriosis might be associated with the decrease of endometrial receptivity.