Background: Polycystic ovarian syndrome (PCOS) is an endocrine-related disease related to abnormal folliculogenesis and is a leading cause of infertility worldwide. Inhibition of granulosa cells (GCs) proliferation and increased GCs apoptosis have been identified as the major factors in aberrant follicle maturation.Methods: USP25 and PTEN expression in GCs from women with and without PCOS was analyzed using Western blotting. A PCOS-like mouse model was constructed using USP25 knockout and wild-type mice to explore the role of USP25 in PCOS. The human granular cell line KGN was cultured for proliferation and apoptosis assays, and the effect of USP25 on PTEN was investigated after transfection with shRNA-USP25 lentivirus.Results: USP25 expression was found to be elevated in patients and mice with PCOS. With mouse model, we observed a reduction in PCOS symptoms in mice after USP25 deletion. Increased proliferation, reduced apoptosis, activation of the phosphoinositide-3-kinase (PI3K)/protein kinase B (AKT) signaling pathway and decreased PTEN expression were found in KGN cells after USP25 knockdown. Finally, we verified that USP25 could deubiquitinate PTEN in KGN cells.Conclusions: In this study, we investigated that USP25 can regulate the PI3K/AKT signaling pathway by deubiquitinating PTEN, thus affecting the proliferation and apoptosis of GCs and contributing to the pathogenesis of PCOS.

Recurrent pregnancy loss (RPL) is a common and severe pathological pregnancy, whose pathogenesis is not fully understood. With the development of epigenetics, the study of DNA methylation, provides a new perspective on the pathogenesis and therapy of RPL. The abnormal DNA methylation of imprinted genes, placenta-specific genes, immune-related genes and sperm DNA may, directly or indirectly, affect embryo implantation, growth and development, leading to the occurrence of RPL. In addition, the unique immune tolerogenic microenvironment formed at the maternal-fetal interface has an irreplaceable effect on the maintenance of pregnancy. In view of these, changes in the cellular components of the maternal-fetal immune microenvironment and the regulation of DNA methylation have attracted a lot of research interest. This review summarizes the research progress of DNA methylation involved in the occurrence of RPL and the regulation of the maternal-fetal immune microenvironment. The review provides insights into the personalized diagnosis and treatment of RPL.

Patients with recurrent pregnancy loss (RPL) account for approximately 1%-5% of women aiming to achieve childbirth. Although studies have shown that RPL is associated with failure of endometrial decidualization, placental dysfunction, and immune microenvironment disorder at the maternal-fetal interface, the exact pathogenesis remains unknown. With the development of high-throughput technology, more studies have focused on the genomics, transcriptomics, proteomics and metabolomics of RPL, and new gene mutations and new biomarkers of RPL have been discovered, providing an opportunity to explore the pathogenesis of RPL from different biological processes. Bioinformatics analyses of these differentially expressed genes, proteins and metabolites also reflect the biological pathways involved in RPL, laying a foundation for further research. In this review, we summarize the findings of omics studies investigating decidual tissue, villous tissue and blood from patients with RPL and identify some possible limitations of current studies.

Immunity and metabolism are interdependent and coordinated, which are the core mechanisms for the body to maintain homeostasis. In tumor immunology research, immunometabolism has been a research hotspot and has achieved groundbreaking changes in recent years. However, in the field of maternal-fetal medicine, research on immunometabolism is still lagging. Reports directly investigating the roles of immunometabolism in the endometrial microenvironment and regulation of maternal-fetal immune tolerance are relatively few. This review highlights the leading techniques used to study immunometabolism and their development, the immune cells at the maternal-fetal interface and their metabolic features required for the implementation of their functions, explores the interaction between immunometabolism and pregnancy regulation based on little evidence and clues, and attempts to propose some new research directions and perspectives.

PFAS (per- and polyfluoroalkyl substances) have been extensively used across numerous industries and consumer goods. Due to their high persistence and mobility, they are ubiquitous in the environment. Exposure to PFAS occurs in people via multiple pathways such as dermal contact, water supply, air inhalation, and dietary intake. Even if some PFAS are being phased out because of their persistent presence in the environment and harmful impacts on human health, mixes of replacement and legacy PFAS will continue to pollute the ecosystem. Numerous toxicological investigations have revealed harmful effects of PFAS exposure on female reproductive health, e.g., polycystic ovaries syndrome, premature ovarian failure, endometriosis, reproductive system tumors, pregnancy complications, and adverse pregnancy outcomes. Despite extensive epidemiological studies on the reproductive toxicity of PFAS, research findings remain inconsistent, and the underlying mechanisms are not well understood. In this review, we give an in-depth description of the sources and pathways of PFAS, and then review the reproductive toxicity of PFAS and its possible mechanisms.

Granulocyte colony-stimulating factor (G-CSF) is one of the cytokines which plays important roles in embryo implantation and normal pregnancy. At the maternal-fetal interface, G-CSF can be synthesized by multiple cells, and participates in regulation of trophoblast development, endometrial decidualization, placental metabolism and angiogenesis. Moreover, as an important medium of intercellular communication, G-CSF has also been shown to exert key roles in crosstalk between cellular components at the maternal-fetal interface. Recently, our study demonstrated that G-CSF derived from M2 macrophage could promote trophoblasts invasion and migration through activating PI3K/AKT/Erk1/2 pathway, thereby involving in normal pregnancy program. Herein, we will summarize the role and regulation of G-CSF in normal pregnancy and reproductive-related disease, and the clinical applications of G-CSF in patients undergoing in vitro fertilization with thin endometrium, repeated implantation failure, and women suffered with recurrent spontaneous abortion.