AKT1 and obesity due to melanocortin 4 receptor deficiency: In most cases, including obesity and metal exposures, the determinant factor for a defective acrosomal function is oxidative stress, which results in multiple molecular alterations, such as protein carbonylation and lipoperoxidation, thereby in sperm damage to cellular membranes or proteins involved in pathways regulating acrosomal exocytosis, such as protein kinase B (Akt), serine/threonine kinases, G proteins, phospholipase C, CatSper channels, etc. [58, 59].