Insights into leptin signaling and male reproductive health: the missing link between overweight and subfertility?

2018 ◽  
Vol 475 (22) ◽  
pp. 3535-3560 ◽  
Author(s):  
Bruno P. Moreira ◽  
Mariana P. Monteiro ◽  
Mário Sousa ◽  
Pedro F. Oliveira ◽  
Marco G. Alves

Obesity stands as one of the greatest healthcare challenges of the 21st century. Obesity in reproductive-age men is ever more frequent and is reaching upsetting levels. At the same time, fertility has taken an inverse direction and is decreasing, leading to an increased demand for fertility treatments. In half of infertile couples, there is a male factor alone or combined with a female factor. Furthermore, male fertility parameters such as sperm count and concentration went on a downward spiral during the last few decades and are now approaching the minimum levels established to achieve successful fertilization. Hence, the hypothesis that obesity and deleterious effects in male reproductive health, as reflected in deterioration of sperm parameters, are somehow related is tempting. Most often, overweight and obese individuals present leptin levels directly proportional to the increased fat mass. Leptin, besides the well-described central hypothalamic effects, also acts in several peripheral organs, including the testes, thus highlighting a possible regulatory role in male reproductive function. In the last years, research focusing on leptin effects in male reproductive function has unveiled additional roles and molecular mechanisms of action for this hormone at the testicular level. Herein, we summarize the novel molecular signals linking metabolism and male reproductive function with a focus on leptin signaling, mitochondria and relevant pathways for the nutritional support of spermatogenesis.

2021 ◽  
pp. 194173812110553
Author(s):  
Behzad Hajizadeh Maleki ◽  
Bakhtyar Tartibian ◽  
Mohammad Chehrazi

Context: Mounting evidence from the literature suggests that different types of training interventions can be successful at improving several aspects of male reproductive function in both fertile and infertile populations. Objective: The aim of this study was to evaluate the effectiveness of exercise training on male factor infertility and seminal markers of inflammation. Data Sources: We searched PubMed, CISCOM, Springer, Elsevier Science, Cochrane Central Register of Controlled Trials, Scopus, PEDro, Ovid (Medline, EMBASE, PsycINFO), Sport Discus, Orbis, CINAHL, Web of Science, ProQuest, and the ClinicalTrials.gov registry for randomized controlled trials (RCTs) that analyzed the impacts of selected types of exercise interventions on markers of male reproductive function and reproductive performance. Study Selection: A total of 336 records were identified, of which we included 7 trials reporting on 2641 fertile and infertile men in the systematic review and network meta-analysis. Level of Evidence: Level 1 (because this is a systematic review of RCTs). Data Extraction: The data included the study design, participant characteristics, inclusion and exclusion, intervention characteristics, outcome measures, and the main results of the study. Results: The results of network meta-analysis showed that, compared with a nonintervention control group, the top-ranking interventions for pregnancy rate were for combined aerobic and resistance training (CET) (relative risk [RR] = 27.81), moderate-intensity continuous training (MICT) (RR = 26.67), resistance training (RT) (RR = 12.54), high-intensity continuous training (HICT) (RR = 5.55), and high-intensity interval training (HIIT) (RR = 4.63). While the top-ranking interventions for live birth rate were for MICT (RR = 10.05), RT (RR = 4.92), HIIT (RR = 4.38), CET (RR = 2.20), and HICT (RR = 1.55). Also, with the following order of effectiveness, 5 training strategies were significantly better at improving semen quality parameters (CET > MICT > HICT > RT > HIIT), seminal markers of oxidative stress (CET > MICT > HIIT > HICT > RT), seminal markers of inflammation (CET > MICT > HIIT > RT > HICT), as well as measures of body composition and VO2max (CET > HICT > MICT > HIIT > RT). Conclusion: The review recommends that the intervention with the highest probability of being the best approach out of all available options for improving the male factor infertility was for CET.


Author(s):  
Michael T. Mbizvo ◽  
Tendai M. Chiware

Male reproductive function entails complex processes, involving coordinated interactions between molecular structures within the gonadal and hormonal pathways, tightly regulated by the hypothalamic–pituitary gonadal axis. Studies in men and animal models continue to unravel these processes from embryonic urogenital development to gonadal and urogenital ducts function. The hypothalamic decapeptide gonadotropin-releasing hormone is released into the hypophyseal portal circulation in a pulsatile fashion. It acts on the gonadotropes to produce the gonadotropins, the main trophic hormones acting on the testis to regulate sperm production. This endocrine control is complemented by paracrine and autocrine regulation arising from the testis, where germ cells originate, modulated by growth factors and local regulators arising within the testis. The process of spermatogenesis, originating in seminiferous tubules, is characterized by stem cell proliferation and differentiation, meiotic divisions, expression of transcriptional regulators, through to morphological changes which include cytoplasm reorganization and flagellum development. Metabolic processes and signal transduction pathways facilitate the functional motion and transport of sperm to the site of fertilization. The normal sperm structure or morphology acquired during spermatogenesis, epididymal maturation, sperm capacitation including motility, and subsequent acrosome reaction are all critical events in the acquisition of sperm fertilizing ability. Generation of the male gamete is assured through adequate gonadal function, involving complex differentiation processes and regulation, during spermiogenesis and spermatogenesis. Sperm functional changes are acquired during epididymal transit, and functional motion is maintained in the female reproductive tract, involving activation of signaling processes and transduction pathways. Infertility can arise in the male, from spermatogenic failure, sperm functional quality, obstruction and other factors, but causes remain unknown in a large proportion of affected men. Semen analysis, complemented by the clinical picture, remains the mainstay of male infertility investigation. Assisted reproductive technology has proved useful in instances where the cause is not treatable. Complications from sexually transmitted infections could lead to male infertility, by impairing sperm quality, production, or transport through the reproductive tract. Male fecundity denotes the biological capacity of men to reproduce, based on ability to ejaculate normal sperm. Lifestyle, environmental, and endocrine disruptors have been implicated in reduced male fecundity. Interactions between vascular, neurological, hormonal, and psychological factors confer normal sexual function in men. Nocturnal erections begin in early puberty, occurring with REM sleep. Sexual health is an integral part of sexual and reproductive health, while sexual dysfunction, in various forms, is also experienced by some men. Methods of contraception available to men are few, and underused. They include condoms and vasectomy. Enhanced knowledge of male reproductive function and underlying physiological mechanisms, including sperm transit to fertilization, can be catalytic in improvements in assisted reproductive technologies, male infertility diagnosis and treatment, and development of contraceptives for men. The article reviews the processes associated with male reproductive function, dysfunction, physiological processes and infertility, fecundity, approaches to male contraception, and sexual health. It further alludes to knowledge gaps, with a view to spur further research impetus towards advancing sexual and reproductive health in the human male.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Lorena Padilla ◽  
Marina López-Arjona ◽  
Silvia Martinez-Subiela ◽  
Heriberto Rodriguez-Martinez ◽  
Jordi Roca ◽  
...  

Abstract Background Identification of relevant in vivo biomarkers for fertility remains a challenge for the livestock industry. Concentrations of the small peptide hormone oxytocin (OXT), involved in male reproductive function and present in the seminal plasma (SP) of several species could be a robust one. This study characterized concentrations of SP-OXT in ejaculates from boars used in artificial insemination (AI) programs aiming to evaluate its relationship with sperm quality variables and in vivo fertility of their liquid-stored AI-semen. Seminal OXT concentrations (ng/mL) were measured in 169 ejaculates from 61 boars of the Duroc, Pietrain, Landrace and Large White breeds using a direct competitive immunoassay test based on AlphaLISA® technology. Ejaculate (ejaculate volume, sperm concentration, total sperm count) and sperm parameters (motility, viability, intracellular generation of reactive oxygen species, plasma membrane fluidity) were assessed at 0 h and 72 h in AI-semen samples stored at 17 °C. In vivo fertility included only 18 Large White and Landrace boars whose AI-semen was used to inseminated > 100 sows and evaluated both farrowing rate and litter size of 3,167 sows. Results The results showed that SP-OXT differed between boars and between ejaculates within boar (P < 0.05) but not between breeds (Duroc, Pietrain, Landrace and Large White). Ejaculates with higher SP-OXT concentration/mL (hierarchically grouped; P < 0.001) had larger volume and came from younger boars (P < 0.05). Ejaculates of boars showing positive farrowing rate deviation exhibited higher (P < 0.05) SP-OXT concentration/mL than those with negative farrowing rate deviation. Conclusion The SP concentrations of OXT are boar, ejaculate and age dependent, and positively related with ejaculate volume and farrowing rates of liquid-stored semen AI-doses.


2020 ◽  
Vol 21 (16) ◽  
pp. 5761 ◽  
Author(s):  
Ilaria Cimmino ◽  
Francesca Fiory ◽  
Giuseppe Perruolo ◽  
Claudia Miele ◽  
Francesco Beguinot ◽  
...  

Bisphenol A (BPA) is an organic synthetic compound serving as a monomer to produce polycarbonate plastic, widely used in the packaging for food and drinks, medical devices, thermal paper, and dental materials. BPA can contaminate food, beverage, air, and soil. It accumulates in several human tissues and organs and is potentially harmful to human health through different molecular mechanisms. Due to its hormone-like properties, BPA may bind to estrogen receptors, thereby affecting both body weight and tumorigenesis. BPA may also affect metabolism and cancer progression, by interacting with GPR30, and may impair male reproductive function, by binding to androgen receptors. Several transcription factors, including PPARγ, C/EBP, Nrf2, HOX, and HAND2, are involved in BPA action on fat and liver homeostasis, the cardiovascular system, and cancer. Finally, epigenetic changes, such as DNA methylation, histones modification, and changes in microRNAs expression contribute to BPA pathological effects. This review aims to provide an extensive and comprehensive analysis of the most recent evidence about the potential mechanisms by which BPA affects human health.


Author(s):  
P. A. Vuytsik

Introduction. Reproductive problems in marriage are an important component of demographic processes; therefore, attempts to resolve them have not only medical but also social significance. The state of male reproductive health plays an important role in demographic indicators, in particular, in population reproduction. This dictates the need to increase the volume of preventive measures, which requires early detection of reproductive disorders due to the impact of environmental factors, including occupational ones, that have a harmful effect on men. The aim of the study is to develop a prevention program aimed at preserving and improving the reproductive health of employees engaged in harmful working conditions. Materials and methods. To predict the quality of health of a future individual, it is necessary to consider many risk factors that can participate in the development of human pathology. Methods for studying reproductive health disorders in men include both conventional, classical methods of examining men by urologists, andrologists, and expert ones, which allow us to find out the role of harmful factors in the development of reproductive disorders of professional etiology by specialists in occupational medicine. The implementation of a reproductive health program requires monitoring the progress of the actions taken and evaluating their effectiveness. Results. Implementing a reproductive health program requires monitoring the progress of actions and evaluating their effectiveness. Conclusions. The ability to assess the risk of damage to reproductive health and the health of the offspring makes it possible to manage this risk, to prevent and reduce the levels of occupationally determined morbidity and morbidity associated with exposure to harmful factors.


2016 ◽  
Vol 11 (3) ◽  
pp. 654-662 ◽  
Author(s):  
Paweł Jóźków ◽  
Marco Rossato

With expanding knowledge on the health benefits of exercise, there is an increasing demand for information on the andrological consequences of participating in sports. These consequences are especially important in the context of infertility problems worldwide. The so-called “male factor” is reported in up to 50% of couples having trouble with conception. The answer to the question, “Is physical activity good for male reproductive health?” is not straightforward. A number of studies have suggested that significant changes in semen parameters may occur due to sports training of certain types, intensities, and durations. The changes to these parameters vary in scope, direction, and magnitude. Findings in recreational athletes have also differed from those in professional athletes. This review of the current literature suggests that intense physical activity may affect the semen concentration, as well as the number of motile and morphologically normal spermatozoa. Training at higher intensities and with increased loads seems to be associated with more profound changes in semen quality. In recreational athletes, exercise has either a positive or neutral effect on semen parameters. Due to many limitations (e.g., global sperm count trends, concerns about the quality control of sperm evaluations, and new standards for semen analysis), comparisons among historical data and their interpretation are difficult.


2020 ◽  
Vol 2020 ◽  
pp. 1-14
Author(s):  
Sridevi Vaadala ◽  
Naveen Ponneri ◽  
Venkata Shashank Karanam ◽  
Sri Bhashyam Sainath ◽  
Pamanji Sreenivasuala Reddy ◽  
...  

Baicalein (BC), a flavonoid, which lacks the qualities of reproductive health and shows adverse effects, is tested in this study. Inseminated mice were injected with 30, 60, and 90 mg BC/Kg body weight on gestation days 11, 13, 15, and 17. The F1 BC-exposed males of each dosage were divided into six groups. First three groups (n = 6 from each BC dosage) were used for assessment of reproductive performance, the others (n = 4 from each BC dosage) were administered with testosterone 4.16 mg/kg body weight on postnatal days 21, 31, and 41. The reproductive health of adult F1 males at the age of 55 and 60 was tested. Prenatal BC exposure showed reduced fertility after cohabitation with control females. The BC exposure significantly reduced the body weight, tissue indices, and sperm parameters (motility, count, viability, and daily sperm count) and altered the sperm membrane in a hypoosmotic swelling test. A downward trend was observed in testicular steroidogenic marker enzymes (3β- and 17β-steroid dehydrogenases) and serum testosterone, whereas increase in serum titers of FSH and LH along with altered the testicular histology. Conversely, testosterone (4.16 mg/kg body weight) partially recovered reduced male reproductive health by BC. BC impaired male reproductive health due to low levels of testosterone is reverted by external testosterone is evidenced in this study.


2021 ◽  
Vol 27 (4) ◽  
Author(s):  
Julieta B Grosso ◽  
Luciana Zoff ◽  
Karina L Calvo ◽  
María Belén Maraval ◽  
Mariana Perez ◽  
...  

Abstract Decreased fertility is becoming an important social and medical problem and the male factor is involved in at least half of infertility cases. Since conventional semen analysis provides limited prediction of male fertility; in this work, we evaluated the potential use of seminal small RNAs (sRNA) as markers of semen quality in ART. Our bioinformatic analyses of available sRNA-seq databases showed that the most abundant sRNA species in seminal plasma of normozoospermic men are tRNA-derived fragments (tRFs), a novel class of regulatory sRNAs. These molecules not only exert their function within cells but also are released into the extracellular environment where they could carry out signaling functions. To evaluate whether the assessment of seminal tRFs in normozoospermic men has a predictive value for the clinical outcome in ART, we performed a prospective study with couples who underwent ICSI cycles with donated oocytes. The results obtained demonstrated that levels of 5’tRF-Glu-CTC, 5’tRF-Lys-CTT, and 5’tRF-Gly-GCC are significantly elevated in seminal samples from cases with repeated failed ICSI cycles, suggesting a potential association between increased seminal tRFs and unexplained male infertility. Interestingly, these tRFs showed a negative association with seminal testosterone, highlighting their involvement in male endocrinology. Our findings also suggest that tRFs could play a role in modulating male reproductive function in response to physiological stress since they showed significant associations with the levels of sperm DNA fragmentation in couples that achieved pregnancy but not in cases with failed ICSI cycles where seminal cortisol levels correlate with sperm quality.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Martin Blomberg Jensen ◽  
Christine Hjorth Andreassen ◽  
Anne Jørgensen ◽  
John Erik Nielsen ◽  
Li Juel Mortensen ◽  
...  

AbstractInfertile men have few treatment options. Here, we demonstrate that the transmembrane receptor activator of NF-kB ligand (RANKL) signaling system is active in mouse and human testis. RANKL is highly expressed in Sertoli cells and signals through RANK, expressed in most germ cells, whereas the RANKL-inhibitor osteoprotegerin (OPG) is expressed in germ and peritubular cells. OPG treatment increases wild-type mouse sperm counts, and mice with global or Sertoli-specific genetic suppression of Rankl have increased male fertility and sperm counts. Moreover, RANKL levels in seminal fluid are high and distinguishes normal from infertile men with higher specificity than total sperm count. In infertile men, one dose of Denosumab decreases RANKL seminal fluid concentration and increases serum Inhibin-B and anti-Müllerian-hormone levels, but semen quality only in a subgroup. This translational study suggests that RANKL is a regulator of male reproductive function, however, predictive biomarkers for treatment-outcome requires further investigation in placebo-controlled studies.


Health of Man ◽  
2021 ◽  
pp. 66-70
Author(s):  
Yurii Gurzhenko ◽  
Danylo Kaluzhny ◽  
Oksana Feldman

The work demonstrates the influence of undifferentiated connective tissue dysplasia on male reproductive function, shows which dysplastic-dependent pathology of the male genital area affects the spermogram indices in men. Shown are local problems of deep pathophysiological and histological prerequisites in their development of the male factor of infertility in a married couple. The paper demonstrates the importance of the principles of joint work of related specialists at various stages of diagnosis, treatment and subsequent dispensary observation of patients with DSTS, taking into account the polyetiology and multifactorial nature of the pathologies of the genitourinary system caused by DSTS. The main diagnostic criteria for collagenopathies are minor anatomical anomalies of development, namely, the presence of three or more minor anatomical anomalies of development indicates a high probability of morphogenesis disorders in the form of congenital malformations of the male genital area. The role of the unfavorable course of the early prenatal period, during which the influence of an unfavorable factor can lead to one or another anomaly, for many organs, including the reproductive organs in men, has been revealed, since they are associated with DSTS pathology and are caused by a wide representation of connective tissue. It also demonstrated a great role in the development of non-hereditary forms of exposure to environmental factors, which makes it possible to make a correction with the help of appropriate recommendations. The data presented in the robot can be considered as a certain stage in the study of DSTS problems and its impact on the male reproductive system.


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