Alpha-lipoic acid preserves uterine and ovarian integrity in streptozotocin-induced diabetic rats via modulation of TGF-β and HSP70 pathways.

OBJECTIVE

Diabetes mellitus profoundly impairs female reproductive health by inducing uterine atrophy, follicular loss, and hormonal dysregulation. Oxidative stress and profibrotic signaling, particularly transforming growth factor-β (TGF-β), are central to this pathology, while the role of heat shock protein 70 (HSP70) remains insufficiently characterized. Alpha-lipoic acid (ALA), a mitochondrial cofactor and potent antioxidant, has shown efficacy against diabetic complications; however, its protective effects on reproductive tissues in type 1 diabetes are not well established.

METHODS

Thirty adult female Wistar rats were allocated into control, diabetic, and diabetic + ALA groups (n = 10 each). Diabetes was induced by a single intraperitoneal injection of streptozotocin (60 mg/kg). ALA was administered orally (200 mg/kg/day) for four weeks. Histopathological evaluation focused on uterine gland degeneration, stromal fibrosis, and ovarian follicular integrity. Plasma anti-Müllerian hormone (AMH), uterine TGF-β, and ovarian HSP70 levels were quantified using ELISA.

RESULTS

Streptozotocin-induced diabetes caused significant uterine gland degeneration, stromal fibrosis, ovarian follicular loss, reduced AMH, and elevated TGF-β and HSP70 (p < 0.001). ALA treatment attenuated glandular and stromal injury, reduced fibrosis, and improved follicular morphology. Biochemically, ALA increased AMH, decreased uterine TGF-β, and further upregulated ovarian HSP70, indicating activation of cytoprotective pathways. Although glucose levels remained elevated, partial glycemic reduction was observed.

CONCLUSION

ALA exerts antifibrotic and cytoprotective effects in diabetic reproductive tissues, mitigating uterine and ovarian damage through modulation of TGF-β and HSP70 pathways.