Could Leptin Be Responsible for the Reproductive Dysfunction in Obese Men?

Low sperm concentration, increased fraction of morphologically abnormal sperm, and raised levels of markers of oxidative stress are often reported in the seminal plasma of infertile obese males. The precise reason for changes remains unknown. This short review summarises evidence from human and animal studies linking leptin to the reproductive dysfunction reported in obese males and presents a possible mechanism for this based on the available data in the literature. Serum leptin concentrations correlate positively with body fat mass but its precise link to semen abnormalities reported in obese males has yet to be conclusively established. Decreased sperm concentration, increased fraction of morphologically abnormal sperm and increased markers of oxidative stress have been reported following six weeks of daily leptin treatment to normal weight rats. In addition, decreased expression of endogenous antioxidant enzymes and increased expression of respiratory chain enzymes noted in the testes of leptin treated rats increases the propensity to oxidative stress. Besides that, leptin's interference with histone to protamine transition in the DNA of sperm increases the susceptibility of sperm to free radical attack and may explain the often reported higher DNA fragmentation index in sperm of obese males. Concurrent supplementation of melatonin, a natural anti-oxidant, to these rats prevents the effects of leptin. The role of leptin in obesity-related reproductive dysfunction has to be considered seriously and these effects of leptin might involve increased oxidative stress.