Metformin augments major cytoplasmic organization except for spindle organization in oocytes cultured under hyperglycemic and hyperlipidemic conditions: An in vitro study.

The present study aimed to investigate the role of antidiabetic drug metformin on the cytoplasmic organization of oocytes. Germinal vesicle (GV) stage oocytes were collected from adult female Swiss albino mice and subjected to in vitro maturation (IVM) in various experimental groups- control, vehicle control (0.3% ethanol), metformin (50 µg/mL), high glucose and high lipid (HGHL, 10 mM glucose; 150 µM palmitic acid; 75 µM stearic acid and 200 µM oleic acid in ethanol), and HGHL supplemented with metformin. The metaphase II (MII) oocytes were analyzed for lipid accumulation, mitochondrial and endoplasmic reticulum (ER) distribution pattern, oxidative and ER stress, actin filament organization, cortical granule distribution pattern, spindle organization and chromosome alignment. An early polar body extrusion was observed in the HGHL group. However, the maturation rate at 24 h did not differ significantly among the experimental groups compared to the control. The HGHL conditions exhibited significantly higher levels of oxidative stress, ER stress, poor actin filament organization, increased lipid accumulation, altered mitochondrial distribution, spindle abnormalities, and chromosome misalignment compared to the control. Except for spindle organization, supplementation of metformin to the HGHL conditions improved all the parameters (non-significant for ER and actin distribution pattern). These results show that metformin exposure in the culture media helped to improve the hyperglycemia and hyperlipidemia-induced cytoplasmic anomalies except for spindle organization. Given the crucial role of spindle organization in proper chromosome segregation during oocyte maturation and meiotic resumption, the implications of metformin's limitations in this aspect warrant careful evaluation and further investigation.

Curcumin nanocrystals attenuate cyclophosphamide-induced testicular toxicity in mice.

The cancer therapy using cyclophosphamide (CP) has been associated with adverse effects on the testicular function that raises concerns about the future fertility potential among cancer survivors. Curcumin, a polyphenol, has shown to possess a plethora of biological functions including tissue protective effects. In the present study, we investigated the protective effects of curcumin nanocrystals (NC) in mitigation of CP-induced testicular toxicity. Healthy adult (8-10 week) and prepubertal (2 week) male Swiss albino mice were injected with a single dose of CP (200 mg/kg) intraperitoneally (i.p). NC (4 mg/kg, i.p.) was administered every alternate day, for 35 days in adult mice while, a single dose of NC was injected intraperitoneally to prepubertal mice 1 h prior to CP. Administration of multiple doses of NC ameliorated CP-induced testicular toxicity in adult mice, which was evident from the improved sperm functional competence, sperm chromatin condensation, seminiferous tubule architecture and decreased apoptosis in testicular cells. Further, administration of NC 1 h prior to CP in prepubertal mice modulated the expression of genes pertaining to proliferation, pluripotency, DNA damage and DNA repair in spermatogonial cells at 24 h after the treatment. Overall, these results suggest that NC could be a promising chemoprotective agent, which can have potential application in male fertility preservation.