No abstract

Trophoblasts are significant components of the placenta and play crucial roles in maternal-fetal crosstalk. Adequate trophoblast migration and invasion are essential for embryo implantation and healthy pregnancy. Ubiquitin-specific protease 7 (USP7), a member of the deubiquitinating enzyme family, regulates the processes of migration and invasion in multiple tumor cells. However, the effects of USP7 on trophoblasts and its possible mechanism in the development of recurrent spontaneous abortion (RSA) are still unclear. In this study, we analyzed the expression of USP7 in villous tissues obtained from RSA patients and healthy controls, and then GNE-6776 (a USP7-specific inhibitor) and USP7 siRNA were used in a trophoblast cell line, HTR-8/SVneo, to further assess the effect of USP7 on the biological function of trophoblasts. Our results provide convincing evidence that USP7 is downregulated in the placental villous tissues of RSA patients. USP7 was found to have a crucial role in the proliferation, apoptosis, migration, invasion, and epithelial-mesenchymal transition (EMT) process of trophoblast cells. Further experiments revealed that USP7 directly interacted with the enhancer of zeste homolog 2 (EZH2) and regulated the Wnt/β-catenin signaling pathway in trophoblasts. Taken together, these findings indicate the vital role of USP7 in regulating trophoblast proliferation, migration and invasion, thus affecting the pathogenesis of RSA, providing new insights into the important role of USP7 in the maternal-fetal interface.

Background Polycystic ovary syndrome (PCOS) is a multifactorial endocrine disease, which is an important cause of female infertility worldwide. PCOS patients are in a state of chronic low-grade inflammation, and immune imbalance is considered as a potential cause of its pathogenesis. Methods The expression of AOC4P in PCOS and normal ovarian granulosa cells (GCs) was detected by real-time quantitative PCR. KGN cells were induced by dihydrotestosterone at 500 ng/ml to construct PCOS model. After lentivirus-infected, KGN cells were constructed with AOC4P overexpression cell lines, the proliferation and apoptosis levels of KGN cells in AOC4P and NC groups were detected. THP-1-derived macrophages and peripheral blood mononuclear cells (PBMC) were co-cultured with KGN cells for 48h respectively, and the differentiation of macrophages and CD4 + T cells were detected by flow cytometry. Results Decreased AOC4P expression was found in PCOS patients. After constructing PCOS cell model, we observed that overexpression of AOC4P promoted KGN cell proliferation and inhibited apoptosis. After co-culture with AOC4P overexpressed KGN cells, M1 macrophages decreased, M2 macrophages increased, Th1/Th2 ratio increased, and Treg cells increased. Finally, we found that AOC4P inhibited the activation of the nuclear factor κ B (NFκB) pathway in KGN cells. Conclusions In this study, we found that AOC4P regulated the NFκB signaling pathway by inhibiting the phosphorylation of P65, thereby affecting the proliferation and apoptosis of GCs, altering the differentiation of macrophages and T cells, and contributing to the pathogenesis of PCOS.

Background Polycystic ovary syndrome (PCOS) is a multifactorial endocrine disease, which is an important cause of female infertility worldwide. PCOS patients are in a state of chronic low-grade inflammation, and immune imbalance is considered as a potential cause of its pathogenesis. Methods The expression of AOC4P in PCOS and normal ovarian granulosa cells (GCs) was detected by real-time quantitative PCR. KGN cells were induced by dihydrotestosterone at 500 ng/ml to construct PCOS model. After lentivirus-infected, KGN cells were constructed with AOC4P overexpression cell lines, the proliferation and apoptosis levels of KGN cells in AOC4P and NC groups were detected. THP-1-derived macrophages and peripheral blood mononuclear cells (PBMC) were co-cultured with KGN cells for 48h respectively, and the differentiation of macrophages and CD4 + T cells were detected by flow cytometry. Results Decreased AOC4P expression was found in PCOS patients. After constructing PCOS cell model, we observed that overexpression of AOC4P promoted KGN cell proliferation and inhibited apoptosis. After co-culture with AOC4P overexpressed KGN cells, M1 macrophages decreased, M2 macrophages increased, Th1/Th2 ratio increased, and Treg cells increased. Finally, we found that AOC4P inhibited the activation of the nuclear factor κ B (NFκB) pathway in KGN cells. Conclusions In this study, we found that AOC4P regulated the NFκB signaling pathway by inhibiting the phosphorylation of P65, thereby affecting the proliferation and apoptosis of GCs, altering the differentiation of macrophages and T cells, and contributing to the pathogenesis of PCOS.