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Background and Aims: We conducted a study on mice to investigate how osteopontin, a mediator of cell-cell and cell-extracellular matrix (ECM) communication and invasion, influences embryonic development, metabolism, and implantation potential, with confirmation by a 3D in-vitro implantation model. Method: Embryos were collected from female mice and cultured under different conditions: HTF only, HTF supplemented with OPN at different doses, and OPN-supplemented HTF with anti-[Formula: see text]v[Formula: see text]3 Ab or RGS2 inhibitors. Embryo morphology, development, and implantation rates were evaluated. Microarrays were used to evaluate gene expression profiling. Choriocarcinoma JAR and epithelial RL95-2 cell lines were adopted for the in-vitro implantation model. Oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) were used to measure cellular metabolism levels. Results: The supplementation of OPN best enhanced the rate of embryo hatching-out and implantation onto the matrigel at 100 nM, but a higher degeneration rate was seen at a higher concentration ([Formula: see text]200 nM). In OPN-treated embryos, microarray analysis showed 51 significantly down-regulated genes and 60 up-regulated genes, including RGS2. Inhibition of [Formula: see text]v[Formula: see text]3 integrin decreased embryo implantation rates and down-regulated RGS2. Validation of the 3D implantation model using JAR spheroids and RL95-2 monolayer showed a similar effect. OPN also increased OCR and ECAR of the JAR cells, and migration assays revealed increased migration ability in OPN-overexpressed JAR cells, which was then inhibited by [Formula: see text]v[Formula: see text]3 and RGS2 inhibitors. Conclusion: Osteopontin, at a reasonable concentration, could enhance embryo development and implantation by interacting with [Formula: see text]v[Formula: see text]3 integrin, subsequently facilitating the RGS2 pathway. OPN has the potential to be a supplement during in vitro embryo culture in ART intervention.

Background and Aims: We investigated the use of GnRHa pretreatment with different protocols and durations of treatment on pregnancy outcomes in women undergoing FET with artificial cycles (AC-FET). Method: A systematic search of PubMed, EMBASE, Google Scholar, and Cochrane library was performed to include only eligible peer-reviewed studies in English published before September 01, 2022. This review was registered on PROSPERO (CRD42022299259) Results: A total of 41 studies (43021 individuals) were included with low to moderate risk of bias. Overall, GnRHa pretreatment improved clinical pregnancy rate (CPR) (OR=1.27, 95%CI:1.12-1.44), implantation rate (IR) (OR=1.24, 95%CI:1.07-1.45), live birth rate (LBR) (OR=1.31, 95%CI:1.07-1.60) and endometrial thickness (MD=0.16, 95%CI:0.03-0.30). Subgroup analyses of randomized and non-randomized studies both demonstrated the benefits of GnRHa pretreatment in CPR, IR, and LBR. Protocols using depot GnRHa (OR=1.19, 95%CI:1.04-1.36) showed a better LBR than daily GnRHa (OR=1.04, 95%CI:0.93-1.16). Women administered GnRHa for more than one cycle had better CPR (OR=2.01, 95%CI:1.29-3.13) and IR (OR=2.14, 95%CI:0.98-4.67) than those treated with GnRHa within one cycle before FET ([OR=1.18, 95%CI:1.04-1.33] and [OR=1.16, 95%CI:1.01-1.32], respectively). In women with PCOS, pituitary suppression with GnRHa significantly improved CPR (OR=1.24, 95%CI:0.98-4.67), LBR (OR=1.22, 95%CI:1.05-1.42) and reduced the miscarriage rate (OR=0.75, 95%CI:0.59-0.95). In contrast, women with regular menstruation had a higher endometrial thickness (MD=0.16, 95%CI: 0.04-0.28) but no significant improvements in pregnancy outcomes. GnRHa pretreatment considerably improved IR (OR=2.21, 95%CI:1.60-3.07) in women with adenomyosis and CPR (OR=1.74, 95%CI:1.12-2.71), and LBR (OR=1.67, 95%CI:1.06-2.63) in women with endometriosis. Conclusion: GnRHa pretreatment, especially with longer suppression duration and the use of depot GnRHa, demonstrates a beneficial role during AC-FET cycles. Individuals with PCOS benefit from GnRHa pretreatment, though this FET protocol should be carefully considered in ovulatory women with regular menstruation. Albeit having the potential, effectiveness of this protocol on adenomyosis or endometriosis remains controversial and requires more rigorous investigation

Osteopontin (OPN) isoforms, including OPNb and OPNc, promote malignancy and may contribute to the pathogenesis of endometriosis, a benign disorder with multiple characteristics resembling malignant tumors. In our experiments, OPNb and OPNc were significantly overexpressed in both endometriosis and adenomyosis compared to the normal endometrium. Upregulation of CD44v and the epithelial–mesenchymal transition (EMT) process was also present in endometriotic lesions. Overexpression of OPNb and OPNc splicing variants in endometriotic cells evoked morphological changes, actin remodeling, cell proliferation, cell migration, and EMT through binding OPN ligand receptors CD44 and αvβ3, subsequently activating the PI3K and NF-ĸB pathways. We elucidated the causal role of OPN splice variants in regulating endometriotic cell growth, which may promote the development of OPN-targeted therapies for patients suffering from endometriotic disorders.

Abstract Alzheimer’s disease (AD) is a prevalent neurodegenerative disorder afflicting the elderly population worldwide. The identification of potential gene candidates for AD holds promises for diagnostic biomarkers and therapeutic targets. Employing a comprehensive strategy, this study integrated transcriptomic data from diverse data sources, including microarray and single-cell datasets from blood and tissue samples, enabling a detailed exploration of gene expression dynamics. Through this thorough investigation, 19 notable candidate genes were found with consistent expression changes across both blood and tissue datasets, suggesting their potential as biomarkers for AD. In addition, single cell sequencing analysis further highlighted their specific expression in excitatory and inhibitory neurons, the primary functional units in the brain, underscoring their relevance to AD pathology. Moreover, the functional enrichment analysis revealed that three of the candidate genes were downregulated in synaptic signaling pathway. Further validation experiments significantly showed reduced levels of rabphilin-3A (RPH3A) in 3xTg-AD model mice, implying its role in disease pathogenesis. Given its role in neurotransmitter exocytosis and synaptic function, further investigation into RPH3A and its interactions with neurotrophic proteins may provide valuable insights into the complex molecular mechanisms underlying synaptic dysfunction in AD.

This study investigates the effect of GnRHa pretreatment on pregnancy outcomes in artificial endometrial preparation for frozen–thawed embryo transfer (AC-FET) cycles. A systematic review of English language studies published before 1 September 2022, was conducted, excluding conference papers and preprints. Forty-one studies involving 43,021 participants were analyzed using meta-analysis, with a sensitivity analysis ensuring result robustness. The study found that GnRHa pretreatment generally improved the clinical pregnancy rate (CPR), implantation rate (IR), and live birth rate (LBR). However, discrepancies existed between randomized controlled trials (RCTs) and observational studies; RCTs showed no significant differences in outcomes for GnRHa-treated cycles. Depot GnRHa protocols outperformed daily regimens in LBR. Extended GnRHa pretreatment (two to five cycles) significantly improved CPR and IR compared to shorter treatment. Women with polycystic ovary syndrome (PCOS) saw substantial benefits from GnRHa pretreatment, including improved CPR and LBR and reduced miscarriage rates. In contrast, no significant benefits were observed in women with regular menstruation. More rigorous research is needed to solidify these findings.