The Study On The Function And Molecular Mechanism Of Rbbp7 In The Process Of Uterine Stromal Cell Decidualization In Mice

Uterine stromal cells undergo extensive proliferation and differentiation during postimplantation development,a process known as decidualization.While a range of signaling molecules have been demonstrated to play essential roles in this event,its potential epigenetic regulatory mechanisms remained largely unknown.Retinoblastoma binding protein 7(Rbbp7)is a protein reported as a core component of many histone modification and chromatin remodeling complexes.In the present study,our in situ hybridization and immunochemistry analysis firstly revealed a distinctive spatiotemporal expression of Rbbp7 in the mouse uteri during the periimplantation period and in oil-induced deciduoma.Observations of remarkable induction of Rbbp7 expression in uterine stromal cells in response to progesterone-nuclear receptor(PR)signaling pointed toward to its potential physiological significance during postimplantation uterine development.Employing primary murine uterine stromal cell culture and in vitro induced decidualization model combined with stealth RNA knockdown approach,we further demonstrated that the downregulation of Rbbp7 influences stromal cell proliferation,exhibiting dysregulation of cell cycle-related molecules expression and compromises stromal cell decidualization via attenuating histone H4 acetylation and downregulating the expression of Cyclin D3,a molecule playing an important role both in cell proliferation and decidualization process.The results collectively suggested that Rbbp7 is a potentially functional player regulating normal histone acetylation modification and Cyclin D3 expression in stromal cells during postimplantation decidual development.After determined the role of Rbbp7 in murine stromal cell decidualization in vitro,we then utilized Rbbp7 knockout mice to study its function in vivo.Results of reproductive capacity test showed that the deletion of Rbbp7 leads to subfertility in female mice,shown as litter size reduction.The reason may be the abnormal decidualization of stroma during pregnancy,causing fetal retardation or even lost,of which the underlying molecular mechanisms remain to be further studied.Moreover,histone hyperacetylation was reported to be well correlated with stromal-decidual transformation in humans and in this study we found RBBP7 is spatiotemporal expressed in human endometrium,so our study on the function of Rbbp7 in decidualization has high clinical relevance.