Gut microbiota dysbiosis and oxidative damage in high-fat diet-induced impairment of spermatogenesis: Role of protocatechuic acid intervention

In the realm of experimental and epidemiological research, the impact of endotoxemia caused by obesity on male fertility is widely acknowledged. However, the existing body of evidence lacks rigorous studies to substantiate this notion. To address this gap, we have selected protocatechuic acid (PCA) as a potential inhibitor of endotoxemia induced by obesity. This selection is further supported by our utilization of a male model of C57BL/6J mice induced by a high-fat diet (HFD) and the fecal microbiota transplantation assay. Our findings reveal a negative correlation between semen quality and endotoxin levels in the mice model induced by an HFD. Furthermore, intervention with PCA resulted in the restoration of testicular morphology, sperm traits, and function. The transplantation of PCA did not exhibit restorative effects on semen quality, but it did effectively prevent obesity-induced intestinal leakage and endotoxemia. By directly enhancing antioxidant capacity, PCA successfully reversed the fertility reduction caused by obesity. These findings offer substantiation that endotoxemia does not play a significant role in the diminished fertility observed in obese males and propose that the inclusion of dietary antioxidant supplementation can potentially restore male fertility.