Impact of metabolic syndrome on male reproductive functions : role of adipokines

Le syndrome métabolique (SM), dont la prévalence augmente ces dernières décennies, a un impact négatif sur les fonctions de reproduction masculine. Les adipokines sécrétées par le tissu adipeux, jouent un rôle à différents niveaux sur l’axe de reproduction. Ces adipokines très peu étudiées dans le sperme pourraient être le lien entre SM et fertilité altérée. Nous avons donc étudié ces adipokines séminales, tout d’abord en validant la fiabilité de leur dosage dans le plasma séminal (SP) qui est une matrice visqueuse difficilement homogène. Une fois les conditions pré-analytiques déterminées pour obtenir des dosages fiables, nous avons étudié les adipokines séminales chez des patients métaboliquement normaux puis en contexte de SM ou non dans une cohorte de 160 hommes partenaires de couples infertiles. La durée d’infertilité était plus longue chez les hommes présentant un SM. Les adipokines étaient plus concentrées dans le sang que dans le SP, à l’exception de l’Interleukine-6 (IL-6) et de la visfatine. En cas de SM, l’adiponectine diminuait dans le sang de façon attendue, mais augmentait d’un facteur 2,1 dans le SP à la différence des autres adipokines qui variaient selon un profil identique dans le sang que dans le sperme. L’IL-6 séminale était corrélée positivement à la concentration, la mobilité progressive et la vitalité spermatiques. Ces données confirment l’importance de dépister le SM chez les hommes partenaires de couple infertile. Elles suggèrent notamment un rôle des adipokines séminales pour moduler la fertilité des hommes présentant un SM. L’IL-6 jouerait un rôle bénéfique les fonctions spermatiques potentiellement via l’AMPK. Les perspectives de ce travail s’inscrivent dans une prise en charge globale des couples infertiles afin de rétablir un métabolisme optimal à la conception.Metabolic syndrome (MS) which increase since last decades impairs male reproductive functions. Adipokines, secreted by adipose tissue, are involved in reproductive axis. These adipokines are poorly studied in semen and could be the link between MS and fertility. Fistly, we performed pre-analytical conditions to obtain reliable dosages in seminal plasma (SP). Thus, we studied seminal and circulating adipokines in metabolically normal patients and then in 160 male partners of infertile couple which present or not MS. Infertility time was longer in men with MS. Adipokines were more concentrated in blood than SP, except for Interleukin-6 (IL-6) and visfatin. In case of MS, adiponectin was decrease as expected, but 2.1 fold higher in SP than men without MS, unlike other adipokines which variate the same way in blood than in SP. Seminal IL-6 was significantly correlated with sperm concentration, progressive motility and vitality. These data confirm the importance of screening infertile patients for MS. It suggest an involvement of seminal adipokines to modulate fertility in men with MS, and that seminal IL-6 could play a beneficial role on sperm functions probably by AMPK actions. The perspectives of this work are part of a global management of infertile couples to restore optimal metabolism to procreate

Impact du syndrome métabolique sur les fonctions de reproduction masculines : rôle des adipokines

Metabolic syndrome (MS) which increase since last decades impairs male reproductive functions. Adipokines, secreted by adipose tissue, are involved in reproductive axis. These adipokines are poorly studied in semen and could be the link between MS and fertility. Fistly, we performed pre-analytical conditions to obtain reliable dosages in seminal plasma (SP). Thus, we studied seminal and circulating adipokines in metabolically normal patients and then in 160 male partners of infertile couple which present or not MS. Infertility time was longer in men with MS. Adipokines were more concentrated in blood than SP, except for Interleukin-6 (IL-6) and visfatin. In case of MS, adiponectin was decrease as expected, but 2.1 fold higher in SP than men without MS, unlike other adipokines which variate the same way in blood than in SP. Seminal IL-6 was significantly correlated with sperm concentration, progressive motility and vitality. These data confirm the importance of screening infertile patients for MS. It suggest an involvement of seminal adipokines to modulate fertility in men with MS, and that seminal IL-6 could play a beneficial role on sperm functions probably by AMPK actions. The perspectives of this work are part of a global management of infertile couples to restore optimal metabolism to procreate.Le syndrome métabolique (SM), dont la prévalence augmente ces dernières décennies, a un impact négatif sur les fonctions de reproduction masculine. Les adipokines sécrétées par le tissu adipeux, jouent un rôle à différents niveaux sur l’axe de reproduction. Ces adipokines très peu étudiées dans le sperme pourraient être le lien entre SM et fertilité altérée. Nous avons donc étudié ces adipokines séminales, tout d’abord en validant la fiabilité de leur dosage dans le plasma séminal (SP) qui est une matrice visqueuse difficilement homogène. Une fois les conditions pré-analytiques déterminées pour obtenir des dosages fiables, nous avons étudié les adipokines séminales chez des patients métaboliquement normaux puis en contexte de SM ou non dans une cohorte de 160 hommes partenaires de couples infertiles. La durée d’infertilité était plus longue chez les hommes présentant un SM. Les adipokines étaient plus concentrées dans le sang que dans le SP, à l’exception de l’Interleukine-6 (IL-6) et de la visfatine. En cas de SM, l’adiponectine diminuait dans le sang de façon attendue, mais augmentait d’un facteur 2,1 dans le SP à la différence des autres adipokines qui variaient selon un profil identique dans le sang que dans le sperme. L’IL-6 séminale était corrélée positivement à la concentration, la mobilité progressive et la vitalité spermatiques. Ces données confirment l’importance de dépister le SM chez les hommes partenaires de couple infertile. Elles suggèrent notamment un rôle des adipokines séminales pour moduler la fertilité des hommes présentant un SM. L’IL-6 jouerait un rôle bénéfique les fonctions spermatiques potentiellement via l’AMPK. Les perspectives de ce travail s’inscrivent dans une prise en charge globale des couples infertiles afin de rétablir un métabolisme optimal à la conception

Exploring the potential impact of nutritionally actionable genetic polymorphisms on idiopathic male infertility: a review of current evidence

International audienceInfertility affects about 15% of the world's population. In 40%–50% of infertile couples, a male factor underlies the problem, but in about 50% of these cases, the etiology of male infertility remains unexplained. Some clinical data show that lifestyle interventions may contribute to male reproductive health. Cessation of unhealthy habits is suggested for preserving male fertility; there is growing evidence that most preexisting comorbidities, such as obesity and metabolic syndrome, are highly likely to have an impact on male fertility. The analysis of genetic polymorphisms implicated in metabolic activity represents one of the most exciting areas in the study of genetic causes of male infertility. Although these polymorphisms are not directly connected with male infertility, they may have a role in specific conditions associated with it, that is, metabolic disorders and oxidative stress pathway genes that are potentially associated with an increased risk of male infertility due to DNA and cell membrane damage. Some studies have examined the impact of individual genetic differences and gene-diet interactions on male infertility, but their results have not been synthesized. We review the current research to identify genetic variants that could be tested to improve the chances of conceiving spontaneously through personalized diet and/or oral vitamin and mineral supplementation, by examining the science of genetic modifiers of dietary factors that affect nutritional status and male fertility

Adipokines in Semen: Physiopathology and Effects on Spermatozoas

Adipokines are secreted by adipose tissue and could be the link between obesity and infertility. Different studies investigated the involvement of adipokines in reproductive functions but only a few have looked into the male part. This review assesses adipokine functions on male reproductive parameters. Adiponectin seems to have a positive effect on sperm parameters, whereas other adipokines such as resistin or chemerin would have a rather deleterious effect on spermatogenesis. Semen parameters seem to be impacted when resistin and chemerin are increased: indeed, there is a decrease of sperm motility. Sperm morphology is improved when adiponectin is increased. The most studied adipokine, leptin, has a dual effect with a positive effect on sperm at physiological levels and a negative one for high seminal concentrations. Many semen parameters and fertility itself are disturbed according to semen adipokine levels, even if it is not the only interfering element. Taken together, adipokines are found in human and animal semen and most of them or their receptors are expressed in male genital tract. Although the pathophysiological role of adipokines in semen is not clearly elucidated, the adipokines could influence sperm functionality and could be potential biomarkers of male fertility

Seminal plasma adipokines: involvement in human reproductive functions

International audienceInfertility, which increased worldwide over the past few decades, has recently been linked to obesity prevalence. Adipokines, produced by adipose tissue, could be the link between obesity and infertility. The association between circulating adipokines and female infertility has been extensively studied in the last ten years. However, the male aspect has been less investigated, although some adipokines are present in seminal plasma. We have attempted to analyze published studies that measured seminal plasma adipokines and their relationships with semen parameters. Apart from leptin, other seminal adipokines have rarely been studied. Indeed, leptin seems to have a differential role depending on its concentration in the seminal plasma. Thus, it could have a beneficial effect at lower concentrations but a deleterious effect at higher seminal levels. Although some studies are currently available, the roles of leptin and other adipokines in seminal plasma on sperm parameters and their consequences on male fertility remain to be clarified

Optimization of pre-analytical conditions for measurement of biomarkers in seminal plasma: application to adipokines

International audienceA link between obesity and male infertility, concerning particularly semen quality, has been reported. Indeed, circulating levels of adipokines, bioactive peptides secreted by adipose tissue, are correlated with sperm quality in both animals and humans. In this context, levels of adipokines in seminal plasma could influence sperm function and represent useful biomarkers to evaluate fertility-related physiological and pathophysiological conditions

Mechanisms of Adiponectin Action in Fertility: An Overview from Gametogenesis to Gestation in Humans and Animal Models in Normal and Pathological Conditions

International audienceAdiponectin is the most abundant plasma adipokine. It mainly derives from white adipose tissue and plays a key role in the control of energy metabolism thanks to its insulin-sensitising, anti-inflammatory, and antiatherogenic properties. In vitro and in vivo evidence shows that adiponectin could also be one of the hormones controlling the interaction between energy balance and fertility in several species, including humans. Indeed, its two receptors—AdipoR1 and AdipoR2—are expressed in hypothalamic–pituitary–gonadal axis and their activation regulates Kiss, GnRH and gonadotropin expression and/or secretion. In male gonads, adiponectin modulates several functions of both somatic and germ cells, such as steroidogenesis, proliferation, apoptosis, and oxidative stress. In females, it controls steroidogenesis of ovarian granulosa and theca cells, oocyte maturation, and embryo development. Adiponectin receptors were also found in placental and endometrial cells, suggesting that this adipokine might play a crucial role in embryo implantation, trophoblast invasion and foetal growth. The aim of this review is to characterise adiponectin expression and its mechanism of action in male and female reproductive tract. Further, since features of metabolic syndrome are associated with some reproductive diseases, such as polycystic ovary syndrome, gestational diabetes mellitus, preeclampsia, endometriosis, foetal growth restriction and ovarian and endometrial cancers, evidence regarding the emerging role of adiponectin in these disorders is also discussed

Expression of adipokines in seminal fluid of men of normal weight

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Relationships between metabolic status, seminal adipokines, and reproductive functions in men from infertile couples

International audienceObjective Adipokines could be a link between metabolic syndrome (MS) and infertility. While the association between circulating adipokines and fertility has been extensively studied in females, this relationship in males was less investigated, although some adipokines are detectable in seminal plasma (SP). The aim of this study was to determine adipokine levels in blood and SP and to assess the relationships between adipokines, MS and semen parameters in men from infertile couples. Design Male partners of infertile couples referred to four medical French centers were enrolled in years 2013–2016. Methods Subjects ( n = 160) aged 18–45 years were assessed for anthropometric, biochemical, sperm, and circulating hormonal parameters. Leptin, adiponectin, resistin, chemerin, visfatin, and IL-6 were measured in serum and SP. Results Infertility duration was higher in men with than without MS. Adipokine concentrations were higher in blood than in SP, except for IL-6 and visfatin. The most striking result was the significant correlation observed between seminal IL-6 and spermatozoid concentration, progressive motility, and sperm vitality. Moreover, while men with MS exhibited an expected lower adiponectinemia, they displayed 2.1-fold higher adiponectin levels in SP than men without MS. Finally, logistic regression analysis showed that BMI, infertility duration, and adiponectin serum/SP ratio were independently associated with MS. Conclusions These results suggest an involvement of seminal adipokines to modulate fertility in men with MS and that seminal IL-6 could play a beneficial role on sperm functionality. Further mechanistic studies are necessary to investigate the precise roles of these adipokines in male reproduction