Decreased AdipoR1 signaling and its implications for obesity-induced male infertility

Area of Science:

• Reproductive Biology
• Endocrinology
• Molecular Biology

Background:

• Obesity is a known risk factor for male infertility, but the precise mechanisms remain incompletely understood.
• Existing research suggests several pathways linking obesity to male subfertility, necessitating further investigation into molecular underpinnings.

Purpose of the Study:

• To elucidate the role of AdipoR1 (Adiponectin Receptor 1) signaling in obesity-induced male infertility.
• To investigate the impact of AdipoR1 deficiency on testicular function and sperm parameters.
• To evaluate the therapeutic potential of AdipoRon in mitigating obesity-related male infertility.

Main Methods:

• High-fat diet-induced obesity model in male mice.
• Analysis of sperm count, motility, and fertilizing ability.
• Assessment of AdipoR1 gene and protein expression in testicular tissue.
• Evaluation of apoptosis markers, including caspase-6 activity and pro-apoptotic gene expression.
• Use of AdipoR1 knockout mice and AdipoRon administration.

Main Results:

• Male mice fed a high-fat diet exhibited decreased sperm count, motility, and fertilizing ability, alongside reduced AdipoR1 expression and increased apoptosis in testes.
• AdipoR1 knockout mice showed significantly reduced testicular weight, sperm parameters, and AMPK phosphorylation, with elevated apoptosis markers compared to wild-type controls.
• Oral administration of AdipoRon ameliorated sperm motility in obese mice by decreasing caspase-6 activity and testicular apoptosis.

Conclusions:

• Decreased AdipoR1/AMPK signaling in the testes contributes to increased caspase-6 activity and apoptosis, likely causing obesity-induced male infertility.
• AdipoR1 plays a critical role in maintaining testicular function and sperm quality.
• AdipoRon demonstrates therapeutic potential for treating male infertility associated with obesity and impaired AdipoR1 signaling.