Metabolic landscape and pathogenic insights: a comprehensive analysis of high ovarian response in infertile women undergoing in vitro fertilization.

BACKGROUND: In the realm of assisted reproduction, a subset of infertile patients demonstrates high ovarian response following controlled ovarian stimulation (COS), with approximately 29.7% facing the risk of Ovarian Hyperstimulation Syndrome (OHSS). Management of OHSS risk often necessitates embryo transfer cancellation, leading to delayed prospects of successful pregnancy and significant psychological distress. Regrettably, these patients have received limited research attention, particularly regarding their metabolic profile. In this study, we aim to utilize gas chromatography-mass spectrometry (GC-MS) to reveal these patients' unique serum metabolic profiles and provide insights into the disease's pathogenesis. METHODS: We categorized 145 infertile women into two main groups: the CON infertility group from tubal infertility patients and the Polycystic Ovary Syndrome (PCOS) infertility group. Within these groups, we further subdivided them into four categories: patients with normal ovarian response (CON-NOR group), patients with high ovarian response and at risk for OHSS (CON-HOR group) within the CON group, as well as patients with normal ovarian response (PCOS-NOR group) and patients with high ovarian response and at risk for OHSS (PCOS-HOR group) within the PCOS group. Serum metabolic profiles were analyzed using GC-MS. The risk criteria for OHSS were: the number of developing follicles > 20, peak Estradiol (E2) > 4000pg/mL, and Anti-Müllerian Hormone (AMH) levels > 4.5ng/mL. RESULTS: The serum metabolomics analysis revealed four different metabolites within the CON group and 14 within the PCOS group. Remarkably, 10-pentadecenoic acid emerged as a discernible risk metabolite for the CON-HOR, also found to be a differential metabolite between CON-NOR and PCOS groups. cysteine and 5-methoxytryptamine were also identified as risk metabolites for the PCOS-HOR. Furthermore, KEGG analysis unveiled significant enrichment of the aminoacyl-tRNA biosynthesis pathway among the metabolites differing between PCOS-NOR and PCOS-HOR. CONCLUSION: Our study highlights significant metabolite differences between patients with normal ovarian response and those with high ovarian response and at risk for OHSS within both the tubal infertility control group and PCOS infertility group. Importantly, we observe metabolic similarities between patients with PCOS and those with a high ovarian response but without PCOS, suggesting potential parallels in their underlying causes.

MiR-1 targets PIK3CA and inhibits tumorigenic properties of A549 cells.

MicroRNAs are small endogenous RNAs that play important roles in the pathogenesis of human diseases, including malignancy. MicroRNA-1 (miR-1) is downregulated in non-small cell lung cancer (NSCLC); however, the underlying mechanisms by which it suppresses tumorigenesis in NSCLC are largely unknown. We investigated whether phosphoinositide-3-kinase catalytic subunit alpha (PIK3CA) was a novel target of miR-1 in the NSCLC cell line A549, and the mechanism of miR-1 inhibition of the tumorigenic properties of A549 cells is discussed. The influence of miR-1 on A549 cells was studied by transfection with miR-1 mimics or inhibitor. MiR-1 overexpression led to downregulation of PIK3CA protein, but not mRNA by western blot and quantitative real-time PCR, respectively. The dual-luciferase reporter assay confirmed that miR-1 targeted PIK3CA directly. PIK3CA downregulation by miR-1 mimics led to a significant reduction of phosphorylated Akt and survivin protein, the downstream targets of the PI3K/Akt pathway. Cell proliferation was studied using a cell counting kit. Migration and invasion were evaluated by Transwell and Matrigel assays, respectively. Cell cycle and apoptosis were detected by flow cytometry. The results were that miR-1 upregulation inhibited A549 cell proliferation, migration, and invasion. These findings indicate that miR-1 may play an important role in the pathogenesis of NSCLC by regulating PIK3CA through the PI3K/Akt pathway. Increasing miR-1 expression may provide a novel approach for NSCLC treatment.