In the last two decades, evidence from human and animal studies suggests that paternal obesity around the time of conception can have adverse effects on offspring health through developmental programming. This may make significant contributions to the current epidemic of obesity and related metabolic and reproductive complications like diabetes, cardiovascular disease, and subfertility/infertility. To date, changes in seminal fluid composition, sperm DNA methylation, histone composition, small non-coding RNAs, and sperm DNA damage have been proposed as potential underpinning mechanism to program offspring health. In this review, we discuss current human and rodent evidence on the impact of paternal obesity/overnutrition on offspring health, followed by the proposed mechanisms, with a focus on sperm DNA damage underpinning paternal programming. We also summarize the different intervention strategies implemented to minimize effects of paternal obesity. Upon critical review of literature, we find that obesity-induced altered sperm quality in father is linked with compromised offspring health. Paternal exercise intervention before conception has been shown to improve metabolic health. Further work to explore the mechanisms underlying benefits of paternal exercise on offspring are warranted. Conversion to healthy diets and micronutrient supplementation during pre-conception have shown some positive impacts towards minimizing the impact of paternal obesity on offspring. Pharmacological approaches e.g., metformin are also being applied. Thus, interventions in the obese father may ameliorate the potential detrimental impacts of paternal obesity on offspring.

Purpose Emerging evidence from rodent studies suggests that high-fat-diet (HFD)-induced obesity is characterized by increased oxidative damage in sperm and testis. However, interventions using micronutrient supplementation to mitigate oxidative damage in obesity have not been extensively studied. This study aimed to investigate the effect of an antioxidant-based micronutrient supplement (added folate, vitamin B6, choline, betaine, and zinc) on sperm and testicular oxidative damage in HFD-fed male Sprague Dawley rats. Methods Rats (3-weeks-old, 12/group) were weaned onto control (C) or HFD (H) or these diets with micronutrient supplement (CS; HS); sperm and testis were harvested at 30.5 weeks. To assess oxidative stress and antioxidant capacity in testis, levels of malondialdehyde (MDA), glutathione (GSH), folate and susceptibility index (SI) of pro-oxidative damage, mRNA expression of Nrf2, NFκB-p65, IL-6, IL-10 and TNF-α, in addition to superoxide-dismutase (SOD), catalase and glutathione-peroxidase (GPx) activities were measured. 8-hydroxy-2-deoxyguanosine (8-OHdG) were assessed in both sperm and testis. Results HFD-fed rats had significantly increased 8-OHdG content in sperm and testis, increased testicular SI, decreased testicular weight, SOD and GPx activity compared to control. Strikingly, supplementation of HFD appeared to significantly reduce 8-OHdG in sperm and testis (22% and 24.3%, respectively), reduce testicular SI and MDA content (28% and 40%, respectively), increase testicular weight (24%), SOD and GPX activity (30% and 70%, respectively) and GSH content (19%). Moreover, supplementation had significant impact to increase testicular folate content regardless of diet. Furthermore, an overall effect of supplementation to increase testicular mRNA expression of Nrf2 was observed across groups. Interestingly, testicular SI was positively correlated with sperm and testicular 8-OHdG and MDA content, suggesting a critical role of testicular antioxidant activity to combat oxidative damage in sperm and testis. Conclusion Our findings suggest that antioxidant-based micronutrient supplement has the potential to interrupt HFD-induced sperm and testicular oxidative damage by improving testicular antioxidant capacity. Graphical abstract