Work

Activation of the apolipoprotein A1-SRB1 pathway by PD-MSCs decreases vascular permeability in ovaries with lipotoxicity

Year: 2026

Type: article

Abstract: ABSTRACT Objective Excessive cholesterol causes lipid accumulation and plaque buildup in blood vessels, reducing blood supply and ovarian function. The apolipoprotein A1 (ApoA1)-scavenger receptor class B member 1 (SRB1) signaling is crucial in lipid-induced vascular permeability and ovarian steroidogenesis. We previously reported that placenta-derived mesenchymal stem cells (PD-MSCs) improve ovarian function through glucose metabolism and antioxidant effects in a metabolic disorder rat model treated-TAA. However, their therapeutic correlation between ovarian and vascular functions remains unclear. In this study, we analyzed whether PD-MSCs activate ApoA1-SRB1 signaling in a metabolic disorder rat model, and whether their activation modulated vascular permeability and thereby alleviatees ovarian dysfunction. Approach & Results The ovarian metabolic disorder model was established by intraperitoneal injection of thioacetamide (TAA), a lipid toxicity inducer, twice weekly for 12 weeks. After 8 weeks of TAA administration, PD-MSCs (2x10 6 cells) were transplanted via tail vein. After sacrificed at 12 weeks, the expressions of factors for vascular permeability and follicular development were analyzed. PD-MSC transplantation (Tx) significantly decreased lipid accumulation in both blood and ovarian tissues. Additionally, increased ApoA1 expression induced by PD- MSCs triggered SRB1 activation and decreased vascular permeability via eNOS expression in ovarian tissues from patients with metabolic diseases (* p <0.05). Furthermore, the expression of genes related to vascular permeability (e.g., eNOS and Erg-3) and steroidogenesis was significantly greater in the PD-MSC Tx group than in the sham group (* p <0.05). Conclusions: These findings suggest that PD-MSCs normalize vascular function via the ApoA1-SRB1 pathway in ovarian diseases associated with lipid toxicity, suggesting a novel strategy for treating reproductive disorders linked to metabolic dysfunction. Highlights PD-MSCs significantly decreased lipid accumulation in both blood and ovarian tissues, alleviating lipid-induced ovarian dysfunction. PD-MSCs enhanced ApoA1-SRB1 signaling, which activated eNOS expression and reduced vascular permeability in ovarian tissues. PD-MSC treatment improved vascular and steroidogenic gene expression, improving ovarian function in metabolic disorder models.

Source: Stem Cell Research & Therapy

DOI: 10.1186/s13287-026-05238-4