Yufan Song

Metabolic reprogramming at the maternal–fetal interface remodels enzymes, metabolites, and pathways to orchestrate decidualization, placentation, and immune tolerance, thereby sustaining cellular homeostasis and maternal-fetal adaptation. Disruption of this precisely coordinated metabolic reprogramming impairs these processes, contributing to recurrent pregnancy loss (RPL). This review focuses on the two most abundant cell types at the maternal–fetal interface: maternal-derived decidual stromal cells (DSCs) and embryo-derived trophoblasts, and systematically delineates their metabolic reprogramming in healthy pregnancy versus RPL. Recent advances reveal that altered glucose, lipid, amino acid, redox, and one-carbon metabolism in DSCs and trophoblasts drives defective decidualization, placentation, and immune tolerance, offering novel mechanistic insights into RPL etiology. These findings highlight potential metabolic biomarkers and therapeutic strategies, bridging mechanistic discoveries with translational opportunities for RPL.

Backgrounds: Premature ovarian insufficiency (POI) is a clinical syndrome characterized by premature ovarian dysfunction, amenorrhea, and infertility. Ferulic acid (FA) is a prominent bioactive phenolic compound derived from traditional Chinese herbs Angelica sinensis (Oliv.) Diels and Ligusticum chuanxiong Hort. These herbs are commonly used to treat gynecological disorders including menstrual irregularities and infertility, and are known to modulate endoplasmic reticulum (ER) stress. However, the therapeutic potential and molecular mechanisms of FA in the context of POI remain largely unexplored. This study aimed to investigate the protective effects of FA against POI and to elucidate the underlying pharmacological mechanisms. Methods: In vivo, a mouse model of POI was established via a single intraperitoneal injection of cyclophosphamide (CTX; 120 mg/kg), and using FA for 28 days of continuous gavage to observe its therapeutic effect. Ovarian function and pathological changes were assessed by hormone levels, follicle development and oxidative stress (OS) level. In vitro, the effects of FA were examined using 4-hydroperoxy cyclophosphamide (4-OHCP)-treated KGN granulosa cells. Transcriptome sequencing, molecular docking, and molecular dynamics simulations were employed to identify potential targets of FA. Results: Our findings demonstrated that FA administration helped preserve regular estrous cycles, promoted follicle development and hormone secretion, and attenuated OS in both ovarian tissue and granulosa cells (GCs). Transcriptomic profiling combined with molecular docking and molecular dynamics simulations suggested that FA potentially targets key ER stress proteins, specifically Grp78 and Perk. Further in vivo and in vitro experiments confirmed that FA alleviates ER stress by inhibiting the overactivation of the Perk/eIF2α/ATF4/CHOP signaling pathway. Notably, the protective effects of FA were comparable to those of the ER stress inhibitor 4-Phenylbutyric acid (4-PBA) and were reversed by the ER stress activator tunicamycin (TM). Additionally, FA downregulates ERO1α expression, further blocking secondary oxidative damage triggered by ER stress. In KGN cells, FA significantly inhibits 4-OHCP-induced apoptosis and upregulates the anti-apoptotic proteins BCL-2 and BCL-xL, exhibiting efficacy similar to 4-PBA. Conclusions: FA improves ovarian function in CTX-induced POI by coordinately regulating OS and ER stress, inhibiting the Perk/eIF2α/ATF4/CHOP pathway, and suppressing GC apoptosis. These findings provide experimental evidence supporting FA as a potential therapeutic candidate for POI.

Background: The rising prevalence of metabolic disorders characterized by dyslipidemia and impaired glucose metabolism has increased interest in effective nutritional supplements. This systematic review and meta‐analysis was conducted to evaluate the effects of coenzyme Q10 (CoQ10) on lipid profile, glycemic control, and inflammatory markers. Methods: PubMed, Web of Science, Scopus, Embase, Cochrane Library, and ClinicalTrials.gov were searched for eligible randomized controlled trials (RCTs). Random‐effects models were applied to pool weighted mean differences (WMDs) or standardized mean differences (SMDs) with 95% confidence intervals (CIs). Results: A total of 64 RCTs (3422 participants) were included. Lipid profile: CoQ10 supplementation significantly improved blood triglyceride (TG, WMD = −5.67 mg/dL; 95% CI: −10.57, −0.77; p = 0.023), total cholesterol (TC, WMD = −4.86 mg/dL; 95% CI: −8.41, −1.30; p = 0.007), high‐density lipoprotein cholesterol (HDL‐C, WMD = 1.07 mg/dL; 95% CI: 0.22, 1.92; p = 0.013), and low‐density lipoprotein cholesterol (LDL‐C, WMD = −3.98 mg/dL; 95% CI: −7.00, −0.97; p = 0.010). Glycemic control: CoQ10 significantly reduced hemoglobin A1C (HbA1c, WMD = −0.22 % ; 95% CI: −0.37, −0.06; p = 0.006), fasting glucose (WMD = −10.07 mg/dL; 95% CI: −14.75, −5.39; p < 0.001), fasting insulin (FINS, WMD = −2.94 μ IU/mL; 95% CI: −4.63, −1.25; p = 0.001), and homeostasis model assessment–insulin resistance (HOMA‐IR, WMD = −0.82; 95% CI: −1.36, −0.28; p = 0.003). Inflammatory markers: CoQ10 significantly decreased C‐reactive protein (CRP, WMD = −0.44 mg/L; 95% CI: −0.79, −0.09; p = 0.013), tumor necrosis factor‐ α (TNF‐ α , SMD = −1.01; 95% CI: −1.56, −0.64; p = 0.013), and interleukin‐6 (IL‐6, SMD = −0.42; 95% CI: −0.79, −0.05; p = 0.027) levels. Conclusions: CoQ10 supplementation has beneficial effects on lipid metabolism, glycemic control, and inflammation among individuals with metabolic disorders.