Melatonin In Seminal Plasma Research Articles

Мелатонин и мужское бесплодие, вызванное окислительным стрессом

Among couples unable to conceive a child, infertility is explained by the male factor in about 50% of cases. The etiology of male infertility remains uncertain in 30-50% of patients. One of the frequent etiological factors of male infertility is oxidative stress, a statusin which an unbalance between the production of reactive oxygen species and the mechanisms of antioxidant protection. Today, the term «male oxidative stressinfertility» has been proposed as a new descriptor for infertile men with a combination of abnormalsperm characteristics and oxidative stress. Along with the use of traditional antioxidants, it is necessary to search for new moleculesto combat oxidative stressin infertile men. A promising strategy is to use melatonin, a hormone secreted by the pineal gland, as an antioxidant. The review examinesthe antioxidant effects of the melatonin metabolic cascade. The results ofstudies on the relationship between the level of melatonin in seminal plasma and male fertility are presented. New scientific data on the protective potential of melatonin against oxidative stress caused by various metabolic disorders, anticancer chemo- and radiation therapy and other pathogenetic conditions and negative effects are presented. The research on the prospects of using melatonin to protectspermatozoa from oxidative damage in the implementation of assisted reproductive technologiesis analyzed. The interim results ofstudies on the possibility of using melatonin as a dietary supplement in infertile men are summarized.

Sperm melatonin receptors, seminal plasma melatonin and semen freezability in goats

Goat bucks are seasonal breeders that show variation in sperm quality, endogenous melatonin (MLT), and presumably in the expression of MLT receptors on the sperm throughout the year, which may modify sperm freezability. The aim of this study was to determine whether sperm freezability is associated with (i) endogenous melatonin levels in seminal plasma and (ii) the expression of sperm plasma membrane melatonin receptors (MT1, MT2). To evaluate this, spermatozoa from seven Saanen goat bucks were cryopreserved throughout the year in Mexico using a standard freezing protocol. Seminal plasma MLT concentrations were determined by ELISA and the expression and localization of MT1 and MT2 were detected by immunocytochemistry and confirmed by western blotting. The recovery rate of progressive motility after thawing was higher in spring than autumn and winter; in contrast, the F pattern (CTC assay) was higher in winter than in the other seasons. A proportional increase in the AR pattern (CTC assay) was smaller in winter than in the other seasons and the proportion of sperm showing high plasma membrane fluidity was higher in spring than in summer and autumn. The seminal plasma MLT concentrations showed no significant interseasonal differences. The MT1 receptor was immunolocalised at the apical region of the sperm head, while MT2 was mainly localised in the neck. The relative expression of MLT receptors showed significant differences between summer and winter for all bands, except at 75 kDa of MT2. In conclusion, there was an association between the relative expression of MT1 and MT2 receptors throughout the year and sperm freezability in goat bucks in México. Post-thaw sperm quality is enhanced in semen samples collected during breeding season.

Improvement of the Seminal Characteristics in Rams Using Agri-Food By-Products Rich in Phytomelatonin

The aim of this study was to evaluate the effect of a phytomelatonin-rich diet, including by-products from the food industry, on ram sperm quality and seminal plasma composition. Melatonin content in several by-products before and after in vitro ruminal and abomasal digestion was determined by HPLC-ESI-MS/MS. Finally, 20% of a mix of grape pulp with pomegranate and tomato pomaces was included in the rams' diet, constituting the phytomelatonin-rich diet. Feeding the rams with this diet resulted in an increase in seminal plasma melatonin levels compared with the control group (commercial diet) in the third month of the study. In addition, percentages higher than those in the control group of morphologically normal viable spermatozoa with a low content of reactive oxygen species were observed from the second month onwards. However, the antioxidant effect does not seem to be exerted through the modulation of the antioxidant enzymes since the analysis of the activities of catalase, glutathione reductase and glutathione peroxidase in seminal plasma revealed no significant differences between the two experimental groups. In conclusion, this study reveals, for the first time, that a phytomelatonin-rich diet can improve seminal characteristics in rams.

Exogenous melatonin advances the ram breeding season and increases testicular function

Governed by melatonin, ovine reproductive seasonality limits production outcomes due to periods of decreased reproductive efficiency. Though it is established that slow-release melatonin implants improve out of season reproductive performance in the ewe, the comprehensive effects of exogenous melatonin in the ram remain inconclusive. This study aimed to ultimately clarify the ability of exogenous melatonin to alter ram reproductive function during the non-breeding season and the subsequent breeding season. Hence, we investigated the effect of exogenous melatonin on reproductive endocrinology, semen quality and production, testicular size and libido in Merino and Poll Dorset rams (n = 31, using a subset of 18 rams for analysis of semen production and quality). Melatonin treatment resulted in elevation of melatonin in seminal plasma from 1–8 weeks post-implantation and in blood plasma at 6 weeks post-implantation. The blood plasma testosterone of implanted rams was greater than controls at both 6 weeks post-implantation and during the following breeding season. Implanted rams exhibited increased testicular size and number of sperm per ejaculate from 3–12 weeks post-implantation but did not demonstrate any change in sperm motility or morphology in response to treatment. Compared to their control counterparts, melatonin-treated Poll Dorset rams exhibited a lower percentage of sperm DNA fragmentation during several weeks of the non-breeding season. Though melatonin increased the likelihood of ejaculate collection in Poll Dorset rams (P < 0.05), libido was otherwise unaffected by treatment. Melatonin did not alter seminal plasma concentrations of inhibin A or Anti-Mullerian hormone, however, for the first time in the ram we have shown Anti-Mullerian hormone to be positively correlated with the number of sperm per ejaculate and sperm motility (r = 0.464 and 0.3242 respectively, P < 0.001), and inhibin A to be correlated to the number of sperm per ejaculate (r = 0.1786, P = 0.0135). These results indicate that melatonin is able to both systemically upregulate reproduction and act directly upon testicular function in the ram.

Men with idiopathic oligoasthenoteratozoospermia exhibit lower serum and seminal plasma melatonin levels: Comparative effect of night-light exposure with fertile males.

Melatonin is a darkness hormone secreted by the pineal gland, which serves a role in idiopathic oligoasthenoteratozoospermia (iOAT). The present study aimed to evaluate the seminal plasma and serum melatonin levels of 50 patients with iOAT and 50 normal fertile controls and the effects of exposure to light at night on semen parameters. Semen analyses were performed according to the World Health Organization 2010 guidelines. Measurements of serum and seminal plasma melatonin, serum TSH, FT3, FT4, free testosterone, prolactin, FSH and LH were performed using ELISA. The overall results revealed that the serum and seminal plasma levels of melatonin were lower in patients with iOAT compared with the control subjects (P=0.0004 and 0.01, respectively). Patients with iOAT who were exposed to light at night exhibited lower serum and seminal plasma melatonin levels compared with those who were not exposed to light at night (P<0.0001 and 0.02, respectively). Additionally, similar significant differences were identified in control subjects exposed to light at night when compared to non-exposed controls. There was a significantly positive correlation between serum melatonin levels and sperm motility in the entire iOAT patient cohort (r=0.614; P<0.0001) and a significantly positive correlation between the serum and seminal plasma melatonin levels in the non-exposed iOAT patient subgroup (r=0.753; P<0.001). Thus, darkness and sleep at night may improve the semen parameters of patients with iOAT, as evidenced by the effects of light exposure at night on the serum and seminal plasma levels of melatonin and, consequently, on semen parameters.

Effects of melatonin administration on seminal plasma metabolites and sperm fertilization competence during the non-reproductive season in ram

The purpose of this study was to investigate the effects of ram melatonin treatment on the sperm quality and metabolite composition of the seminal plasma in the non-breeding season. Four mature rams were treated with 54 mg melatonin in March subcutaneous implants and four untreated rams served as control. At 0, 30, 90 and 120 days semen samples were collected and sperm, separated from seminal plasma, was evaluated for its capacity to fertilize and produce embryos in vitro. Seminal plasma metabolites were extracted and analyzed by capillary electrophoresis/mass spectroscopy. In the resulting electropherograms, the area corresponding to selected metabolites was extracted and quantified. Ram melatonin treatment affected the in vitro fertilization competence of sperm. Blastocyst output increased until 90 days after treatment (27.20 ± 7.35 vs 54.7 ± 4.4% at 0 and 90 days respectively; p < 0.05) while the untreated group did not show statistical differences.In treated rams, the concentration of melatonin in seminal plasma increased from 3.34 ± 1.70 at day 0–9.65 ± 2.89 AU (Arbitrary Units) after 90 days, then decreased to reach the level of the untreated ram after 120 days (p < 0.05). During 90 days after melatonin treatment, an increase (p < 0.05) in seminal plasma concentrations of glutamic acid (6.28 ± 1.53 vs 14.93 ± 1.53 AU at 0 and 90 days respectively), glutamine (16.89 ± 4.65 vs 54.51 ± 4.65 AU), carnitine (22.97 ± 9.81 vs 104.30 ± 9.81 AU), acetyl-carnitine (48.15 ± 17.32 vs 217.69 ± 17.32 AU), choline (1.82 ± 1.55 vs 14.16 ± 1.55 AU) and arginine (1.31 ± 1.08 vs 14.25 ± 1.08 AU) was detected. Tyrosine concentration increased during 30 days from melatonin treatment (12.79 ± 3.93 vs 27.08 ± 3.04 AU) but at 90 days its levels were similar to the untreated group. In conclusion, melatonin treatment during the non-breeding season improves the concentration of several metabolites in seminal plasma and sperm fertilization competence in Sarda breed ram.

Profile and reproductive roles of seminal plasma melatonin of boar ejaculates used in artificial insemination programs.

Melatonin (MLT) is present in seminal plasma (SP) of mammalian species, including pigs, and it is credited with antioxidant properties. This study aims to identify the sources of variation and the role of boar SP MLT on sperm quality and functionality and in vivo fertilizing ability of liquid-stored semen doses used in AI programs. The SP MLT was measured using an ELISA kit in a total of 219 ejaculates collected from 76 boars, and reproductive records of 5,318 AI sows were recorded. Sperm quality was assessed according to motility (computer-aided sperm analysis) and viability (cytometry evaluation). Sperm functionality was assessed according to the cytometric determination of intracellular HO generation, total and mitochondrial O production, and lipid peroxidation in liquid AI semen samples stored at 17°C over 144 h. The concentration of SP MLT differed among seasons ( < 0.01) and day length periods ( < 0.001) of the year, demonstrating that the ejaculates collected during the increasing day length period (9.80 ± 1.38 pg/mL, range: 2.75-21.94) had lower SP MLT concentrations than those collected during the decreasing day length period (16.32 ± 1.67 pg/mL, range: 5.02-35.61). The SP MLT also differed ( < 0.001) among boars, among ejaculates within boar, and among portions within the ejaculate, demonstrating that SP from the first 10 mL of sperm-rich ejaculate fraction (SRF) exhibited lower MLT concentrations than post-SRF. The SP MLT was negatively related ( < 0.001) to mitochondrial O production in viable sperm. The SP MLT did not differ among AI boars ( = 14) hierarchically grouped according to high and low fertility outcomes. In conclusion, SP MLT concentration in AI boars varies depending on the season of ejaculate collection and differs among boars, ejaculates within boar, and portions within ejaculate. The SP MLT may act at the mitochondrial level of sperm by reducing the generation of O. However, this antioxidant role of SP MLT was not reflected in sperm quality or in vivo fertility outcomes of AI semen doses.

Profile and reproductive roles of seminal plasma melatonin of boar ejaculates used in artificial insemination programs

Profile and reproductive roles of seminal plasma melatonin of boar ejaculates used in artificial insemination programs

Melatonin receptors MT1 and MT2 are expressed in spermatozoa from several seasonal and nonseasonal breeder species

Melatonin is a ubiquitous and multipurpose molecule, and one of its roles is to regulate reproduction in some seasonal mammals. Our group has previously reported the variation in the melatonin levels in ram seminal plasma along the year and identified MT1 and MT2 receptors in ram spermatozoa. The objective of this study was to elucidate whether the presence of melatonin receptors (MT1 and MT2) in the sperm plasma membrane, and melatonin in the seminal plasma is related to seasonal breeding. For this purpose, the presence of melatonin receptors and the levels of melatonin in seminal plasma have been examined in several species: donkey and stallion as long-day breeders; red deer as a wild, short-day, highly seasonal breeder (epididymal spermatozoa); bull as a conventional nonseasonal breeder; boar as a seasonal breeder under management techniques; and dog as possible a seasonal breeder not regulated by melatonin. We have detected measurable levels of melatonin in the seminal plasma of all ejaculated semen samples (from donkey, stallion, boar, bull, and dog). Also, and for the first time, we have demonstrated the presence of MT1 and MT2 melatonin receptors in the spermatozoa of all these species, regardless their type of reproduction or sperm source (ejaculated or epididymal), using indirect immunofluorescence techniques and Western blotting. Our findings suggest that melatonin and melatonin receptors may be universally distributed in the reproductive system of mammals and that the sperm melatonin receptors cells may not be necessarily related with seasonal reproduction. Furthermore, the presence of MT1 at the cytoplasmic droplet in immature ejaculated stallion spermatozoa found in one sample and epididymal red deer spermatozoa suggests that melatonin may be involved in specific functions during spermatogenesis and sperm maturation, like protecting spermatozoa from oxidative damage, this activity being mediated through these receptors.

The Relationship between Seminal Melatonin with Sperm Parameters, DNA Fragmentation and Nuclear Maturity in Intra-Cytoplasmic Sperm Injection Candidates.

Melatonin, the chief secretory product of the pineal gland, regulates dynamic physiological adaptations that occur in seasonally breeding mammals as a response to changes in daylight hours. Because of the presence of melatonin in semen and the mem- brane melatonin receptor in spermatozoa, the impact of melatonin on the regulation of male infertility is still questionable. The aim of this study was to determine the effects of endogenous melatonin on human semen parameters (sperm concentration, motility and normal morphology), DNA fragmentation (DF) and nuclear maturity. In this clinical prospective study, semen samples from 75 infer- tile men were routinely analyzed and assessed for melatonin and total antioxidant capac- ity (TAC) levels using the enzyme-linked immunosorbent assay (ELISA) and colorimetric assay kits, respectively. DF was examined by the sperm chromatin dispersion (SCD) test. Acidic aniline blue staining was used to detect chromatin defects in the sperm nuclei. There was no significant correlation between seminal plasma melatonin and TAC with sperm parameters and nuclear maturity. However, we observed a positive significant correlation between DF and melatonin level (r=0.273, P<0.05). Melatonin in seminal plasma is positively correlated with damaged sperm DNA of infertile patients. The mechanism of this phenomenon needs further study.

Melatonin in sperm biology: breaking paradigms.

Melatonin is a ubiquitous molecule, present in a wide range of organisms, and involved in multiple functions. Melatonin relays the information about the photoperiod to the tissues that express melatonin-binding sites in both central and peripheral nervous systems. This hormone has a complex mechanism of action. It can cross the cell plasma membrane and exert its actions in all cells of the body. Certain melatonin actions are mediated by receptors that belong to the superfamily of G-protein-coupled receptors (GPCRs), the MT1 and MT2 membrane. Melatonin can also bind to calmodulin as well as to nuclear receptors of the retinoic acid receptor family, RORα1, RORα2 and RZRβ. The purpose of this review is to report on recent developments in the physiological role of melatonin and its receptors. Specific issues concerning the biological function of melatonin in mammalian seasonal reproduction and spermatozoa are considered. The significance of the continuous presence of melatonin in seminal plasma with a fairly constant concentration is also discussed.

The effect of exogenous melatonin during the non-reproductive season on the seminal plasma hormonal profile and the antioxidant defence system of Rasa Aragonesa rams

The aim of this study was to analyze the effect of melatonin implants, during the non-reproductive season, on the content of melatonin, testosterone and 17-β estradiol levels, and the antioxidant enzymes glutathione peroxidase, glutathione reductase, superoxide dismutase and catalase of seminal plasma in Rasa Aragonesa rams. Five rams were implanted with melatonin, and four others were used as a control group. Seminal plasma was separated from ejaculates collected one week before melatonin treatment until 21 weeks after melatonin placement, and the hormonal levels and the antioxidant enzyme activity were determined. Exogenous melatonin treatment significantly (P<0.05) increased the levels of endogenous melatonin in seminal plasma immediately, and this effect lasted for 14 weeks. Testosterone and 17-β estradiol levels significantly (P<0.05) increased four and eight weeks after melatonin treatment, respectively. As regards the antioxidant enzymes, melatonin treatment significantly increased (P<0.05) glutathione peroxidase and glutathione reductase activity only, and had no effect on superoxide dismutase and catalase. Therefore, melatonin treatment during the non-breeding season modifies the seminal plasma hormonal profile and some antioxidant enzyme activity in Rasa Aragonesa rams.

Melatonin and Sperm Motility/Melatonin und Spermatozoenmotilität

Several substances can interfere with microtubular function eg. colchicine. Melatonin, a hormone secreted by the pineal gland has similar effects as colchicine on microtubules. In this study melatonin levels were determined in both plasma and seminal plasma of patients with good or impaired motility and forward progression. There was no statistically significant difference between the mean plasma and seminal plasma values of patients with good or impaired motility and forward progression. There was no correlation between seminal plasma melatonin and impaired motility or any other semen parameter. There was also no correlation between plasma and seminal plasma concentrations of melatonin. High seminal plasma melatonin concentrations were not necessarily associated with impaired sperm motility. From these it is concluded that seminal plasma melatonin plays no important role in sperm motility.

Melatonin hormone profile in infertile males

Melatonin is a hormone produced by the pineal gland. There is much controversy about its relationship to the male reproductive process. In this study, seminal plasma as well as the serum melatonin levels were studied in different infertile male groups and were correlated with their semen parameters and hormonal levels. One hundred twenty male cases subdivided into six equal groups were consecutively included; fertile normozoospermic men, oligoasthenozoospermia (OA), OA with leucocytospermia, OA with varicocele, non-obstructive azoospermia (NOA) with high serum follicle stimulating hormone (FSH) and NOA with normal FSH. Semen analysis, estimation of melatonin, FSH, testosterone (T) and prolactin (PRL) hormone was carried out. Mean level of serum melatonin was higher than its corresponding seminal concentrations in all investigated groups with a positive correlation between their levels (r = 0.532, p = 0.01). Serum and seminal plasma melatonin levels in all infertile groups were reduced significantly compared with their levels in the fertile group. The lowest concentrations were in OA with leucocytospermia group. Melatonin in both serum and semen demonstrated significant correlation with sperm motility (r = 607, 0.623 respectively, p = 0.01). Serum melatonin correlated positively with serum PRL (r = 0.611, p = 0.01). It may be concluded that melatonin may be involved in the modulation of reproductive neuroendocrine axis in male infertility. Also, low levels of melatonin in semen were observed in infertile groups having reduced sperm motility, leucocytospermia, varicocele and NOA.