Metformin Improves Fertility in Obese Males by Alleviating Oxidative Stress-Induced Blood-Testis Barrier Damage

Figure 7

Model accounting for the mechanism of the metformin-mediated improvement of fertility in obese male mice. In mice on the high-fat diet, the ectopic deposition of adipose in the testis increases the level of oxidative stress, especially the level of ROS, activating NF-κB in the cytoplasm, resulting in an increase in NF-κB in the nuclei of SCs. The latter results in disordered junction protein expression, which leads to the destruction of BTB integrity and then the decline in spermatogenesis and male fertility. Metformin reduces lipid deposition in the testis, relieves oxidative stress in the testis, inhibits excessive activation of NF-κB in SC nuclei, reverses the destruction of the BTB, and hence improves the reproductive function of male mice. In other words, metformin ameliorates the injury to the reproductive function of obese male mice via the ROS-NF-κB pathway. In addition, FSH is decreased in high-fat-diet-fed male mice, and metformin increases the level of FSH in obese male mice, which might play a role in the process of the metformin-mediated improvement of fertility in obese male mice.