Antioxidants positively regulate obesity dependent circRNAs - sperm quality - functional axis

Area of Science:

• Reproductive Biology
• Molecular Biology
• Nutritional Science

Background:

• Obesity-induced systemic oxidative stress and inflammation contribute to male infertility.
• Circular RNAs (circRNAs) are crucial regulators of sperm quality.
• High-fat diet (HFD) impacts spermatic circRNA cargo and associated networks (ceRNETs), potentially affecting sperm oxidative stress and motility.

Purpose of the Study:

• To investigate the efficacy of a bioactive molecule mix in reversing HFD-induced male infertility.
• To evaluate the impact of the formulation on circRNA biogenesis and sperm quality in HFD mice.
• To elucidate the role of paternal ceRNETs in mediating the beneficial effects of the supplement on sperm motility.

Main Methods:

• HFD C57BL6/J male mice were orally treated with a vitamin C, B12, E, selenium-L-methionine, and glutathione (GSH) mix for 4 weeks.
• Assessed endogenous spermatic FUS-dependent backsplicing machinery and circRNA cargo to evaluate circRNA biogenesis.
• Analyzed spermatic viability and motility, and verified findings through an in vitro assay.

Main Results:

• Oral supplementation with the bioactive molecule mix reversed the HFD phenotype in male mice.
• The formulation positively modulated the spermatic circRNA profile by influencing FUS-dependent backsplicing.
• Significant improvements in sperm viability and motility were observed, correlating with circRNA profile recovery.

Conclusions:

• The formulated bioactive molecules effectively counteract HFD-induced male infertility.
• Recovery of the spermatic circRNA profile is a key mechanism underlying the beneficial effects of the supplement on sperm motility.
• These findings highlight the potential of targeted nutritional interventions for managing obesity-related male reproductive dysfunction.