Magnesium glycinate attenuates cyclophosphamide-induced ovarian toxicity in Wistar rats

Cyclophosphamide (CP) is an alkylating chemotherapy agent that causes severe, dose-limiting ovotoxicity, often leading to diminished ovarian reserve. This study investigated the protective efficacy of magnesium glycinate (MgG), a highly bioavailable organic magnesium chelate with antioxidant properties, against CP-induced structural and endocrine ovarian damage. Forty-eight adult female Wistar rats were divided into six groups (n=8): Control, MgG Low-Dose (22.8 mg/kg), MgG High-Dose (32.8 mg/kg), CP-Only (150 mg/kg i.p. on days 1, 3, and 5), and CP co-administered with low or high-dose MgG orally for 21 days. Serum follicle-stimulating hormone (FSH) and luteinizing hormone (LH) were quantified via ELISA. Ovarian histoarchitecture, stromal fibrosis, and glycoprotein barrier integrity were evaluated utilizing Hematoxylin & Eosin, Masson’s Trichrome, and Periodic Acid-Schiff staining. CP intoxication profoundly disrupted the hypothalamic-pituitary-ovarian axis, significantly suppressing serum FSH and LH levels (p < 0.05). Histologically, CP induced massive interstitial hemorrhage, vascular congestion, extensive stromal fibrosis, and the degradation of glycoprotein microenvironments (follicular basement membrane and zona pellucida). Co-administration of MgG dosedependently attenuated these toxicities. The high-dose MgG regimen normalized LH concentrations, upregulated FSH secretion, prevented hemorrhagic necrosis, suppressed aberrant collagen cross-linking, and preserved the structural integrity of critical glycoprotein barriers and developing follicles. Magnesium glycinate successfully mitigates CP-induced ovotoxicity by rescuing vital gonadotropin secretion, suppressing pathological extracellular matrix remodeling, and preserving essential follicular microenvironments, positioning it as a promising adjunct therapy for fertility preservation during gonadotoxic chemotherapy.

Key Words: Cyclophosphamide; ovarian toxicity; magnesium glycinate; oxidative stress; fertility preservation