Melatonin ameliorates the adverse effects of leptin on sperm

Abstract

This study examined the effects of melatonin on leptin-induced changes in sperm parameters in adult rats. Five groups of Sprague-Dawley rats were treated with either leptin or leptin and melatonin or melatonin for 6 weeks. Leptin was given daily via the intraperitoneal route (60 μg kg−1 body weight) and melatonin was given in drinking water (10 mg kg−1 or 20 mg kg−1 body weight per day). Upon completion, sperm count, sperm morphology, 8-hydroxy-2-deoxyguanosine, Comet assay, TUNEL assay, gene expression profiles of antioxidant enzymes, respiratory chain reaction enzymes, DNA damage, and apoptosis genes were estimated. Data were analyzed using ANOVA. Sperm count was significantly lower whereas the fraction of sperm with abnormal morphology, the level of 8-hydroxy-2-deoxyguanosine, and sperm DNA fragmentation were significantly higher in rats treated with leptin only. Microarray analysis revealed significant upregulation of apoptosis-inducing factor, histone acetyl transferase, respiratory chain reaction enzyme, cell necrosis and DNA repair genes, and downregulation of antioxidant enzyme genes in leptin-treated rats. Real-time polymerase chain reaction showed significant decreases in glutathione peroxidase 1 expression with increases in the expression of apoptosis-inducing factor and histone acetyl transferase in leptin-treated rats. There was no change in the gene expression of caspase-3 (CASP-3). In conclusion, the adverse effects of leptin on sperm can be prevented by concurrent melatonin administration.

Glutathione (GSH) improves sperm quality and testicular morphology in streptozotocin-induced diabetic mice

“… 30 31 Even though ROS is needed at low concentration for sperm capacitation and acrosomal reaction, at high concentrations, it is capable of causing damage in a cascade of reactions involving a wide range of biomolecules. 27 32 33 34 Male reproductive organs and gametes are particularly vulnerable to oxidative damage, as testicular tissue and sperm plasma membranes are rich in polyunsaturated fatty acids (PUFA). 35 36 When targeting lipids, oxidant compounds can induce a peroxidation chain reaction that produces several toxic lipid aldehyde species including MDA and 4-HNE.…”

“…Smears were stained with Eosin Y (Leica Biosystems Richmond Inc., Buffalo Grove, IL, USA) and spermatozoa with the following morphologies were considered to be abnormal: (i) headless, (ii) hookless, (iii) double headed, (iv) broken tail, (v) coiled tail, and (vi) double tailed. 27 28 …”

Sperm DNA damage: The possible link between obesity and male infertility, an update of the current literature

“…Whilst all its effects are not yet confirmed, there are clear implications for regulating food intake, body weight, the hypothalamic–pituitary–thyroid and hypothalamic–pituitary–growth hormone axes, bone formation and inflammation 81 . Rodent models also show that exogenous leptin has direct toxic effects on developing spermatocytes, resulting in reduced sperm count, reduced normal morphology and increased ROS and DNA damage 82–84 . Whilst similar studies have not been performed in humans, leptin receptors are present on germ cells and Leydig cells of human testis, and expression is increased in infertile populations, suggesting a similar mechanism 85,86 …”

Leptin and its actions on reproduction in males

“…A more recent study using 60 μg kg −1 body weight of leptin also reached the same conclusions 67. Researchers in the latter studies also found evidence of increased reactive oxygen species (ROS)66 levels, high 8-hydroxy-2-deoxyguanosine (8-OHdG) levels, and increased sperm DNA fragmentation6768 after administering leptin. Incidentally, leptin has been shown to induce ROS formation in phagocytic6970 and nonphagocytic7172 cells and in renal tubular cells by activating nicotinamide adenine dinucleotide phosphate (reduced form) (NADPH) oxidase 73.…”

“…Thus, leptin may increase sperm damage by generating ROS in the seminiferous tubular cells or in the epididymis. That oxidative stress might indeed be involved is also supported by findings that these adverse effects of leptin are prevented by concurrent administration of melatonin, a very powerful antioxidant 68…”