Mouse models of obesity and male fertility: a systematic review and network meta-analysis.

Background: As the problem of obesity‑induced reduction in male fertility is attracting growing concern, we conducted this network meta-analysis to assess the effects of different high-fat diet (HFD) interventions on male fertility in obese mouse models, aiming to identify the most suitable modeling approach for obesity-related male infertility research. Methods: Sixty-three studies were included. Interventions were categorized based on fat proportion and duration into four HFD groups and compared to a normal diet (ND) group. Network meta-analysis assessed outcomes including body weight, relative testes mass and sperm parameters. Results: The network meta-analysis demonstrated that HFD interventions exerted distinct effects on obesity and reproductive indicators in male mice. HFD4, characterized by high dietary fat content and prolonged feeding duration, induced the most significant weight gain and fertility potential loss. Conclusions: Elevated dietary fat content and prolonged HFD intervention are two indispensable synergistic factors for establishing stable mouse models of obesity with reproductive impairment. HFD-induced obesity primarily triggers oligozoospermia and asthenospermia, with negligible impacts on sperm morphology. Given the inherent heterogeneity and incomplete methodological reporting of preclinical animal studies, the present bias assessment and result interpretation remain preliminary. Standardized unified HFD formulations and rigorous, well-designed animal experiments are required in future studies to further validate relevant findings and optimize obese reproductive injury modeling protocols.