scholarly journals RANKL regulates male reproductive function

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.

2020 ◽  
Vol 20 (2) ◽  
pp. 198-202 ◽  
Author(s):  
Mohammad Motamedifar ◽  
Yalda Malekzadegan ◽  
Parisa Namdari ◽  
Behzad Dehghani ◽  
Bahia Namavar Jahromi ◽  
...  

Introduction: Infertility considered as a social and public health issue and estimated that most of these infertile couples are residents of developing countries. Infectious diseases including the history of Sexually Transmitted Infections (STIs) may impact on male reproductive function. Therefore, the present study aimed to investigate the prevalence of bacterial contaminants of semen and probable association with sperm quality of infertile men in Iranian population. Methods: The study population consisted of 200 infertile men and 150 fertile men attending an infertility Center in southwestern Iran during the study period in 2015. The assessment of sperm parameters was according to the World Health Organization (WHO) guidelines. The presumptive pathogens were identified using standard microbiology tests and confirmed by specific PCR primers. Results: The prevalence of bacteriospermia in the semen of the infertile group was significantly higher than that in the fertile group (48% vs. 26.7%, P <0.001). The microbiological analysis of samples showed that the most abundant species of bacteria in semen of infertile men were Chlamydia trachomatis (12.5%) followed by Neisseria gonorrhoeae (11%). On the other hand, in the control group, Lactobacillus spp. (17.3%) was the most isolated pathogen. Results showed that the presence of N. gonorrhoeae, C. trachomatis, Mycoplasma genitalium, Haemophilus, and Klebsiella was significantly associated with sperm abnormality. Conclusion: Based on our findings, it seems that bacteriospermia is associated with alterations in the properties of semen which may lead to a decrease in the fertilization potential of sperm. Therefore, immediate and appropriate treatment is necessary before investigating every other possible cause of infertility.


2014 ◽  
Vol 2014 ◽  
pp. 1-4 ◽  
Author(s):  
D. Živković ◽  
I. Fratrić

Male reproductive function in the general population raises an increased attention due to reports indicating declining sperm counts, increased occurrence of testicular cancer, cryptorchidism, and hypospadias. It is also hypothesized that prolonged exposure of the developing male, during both fetal and postnatal life, to exogenous estrogens could reduce Sertoli cell number and thus reduce sperm output (and sperm counts) in adult life. Fact is that infertility, which is defined as the inability to conceive after 1 year of unprotected intercourse, has a global prevalence of 9%. A male contributory factor is involved in approximately half of these cases, but most of the causes of reduced semen quality and other disturbances of male reproductive function are unknown. In the most affected men (azoospermic men) 15–20% had a prior history of cryptorchidism. The association between the cryptorchidism and infertility is one of the most studied potential causes of infertility. There are numerous studies that accentuate the importance of minipuberty for future fertility. Is it possible that a normal minipuberty ensures normal fertility despite malpositioned testes? And to move away from cryptorchidism, could impaired minipuberty be responsible for fertility problems in men who were born with both testes in their scrotal sacs?


1975 ◽  
Vol 78 (2) ◽  
pp. 373-384 ◽  
Author(s):  
J. Mauss ◽  
G. Börsch ◽  
K. Bormacher ◽  
E. Richter ◽  
G. Leyendecker ◽  
...  

ABSTRACT The effect of long-term testosterone administration on male reproductive function has been investigated in seven healthy young men age 20 to 27 years. Testosterone oenanthate (TOe) was administered in doses of 250 mg per week for 21 weeks. No toxic side-effects were observed. Libido, sexual potency, frequency of sexual intercourse and body hair development generally remained unaffected, but there was a reversible mean weight gain of 3.6 kg during TOe administration. Seminal fluid parameters and radioimmunoassayable serum FSH, LH, testosterone, and androstenedione levels were monitored before, during, and after TOe administration. The serum testosterone rose approximately by a factor of two, while the serum FSH and LH were rapidly suppressed after the initiation of the TOe therapy. The mean sperm concentration fell to values below three million spermatozoa per ml, and changes in sperm motility, the percentage of normal sperm morphology, and seminal fructose concentrations generally paralleled those of the mean sperm concentrations. In contrast, the mean seminal fluid volume and serum androstenedione levels did not change significantly during TOe administration. The mean sperm concentration showed a marked recovery 13 to 16 weeks after TOe withdrawal, but sperm counts remained below pre-treatment levels in three out of seven subjects 25 to 28 weeks after discontinuation of TOe.


Author(s):  
W. N. Li ◽  
M. M. Jia ◽  
Y. Q. Peng ◽  
R. Ding ◽  
L. Q. Fan ◽  
...  

Abstract Background The aim of this study was to provide information on the semen quality pattern of infertile men and age thresholds for semen parameters in China. Methods This was a retrospective cross-sectional study investigating 71,623 infertile men from the Reproductive and Genetic Hospital of CITIC Xiangya in Hunan, China, from 2011 to 2017. The Kruskal-Wallis test, Mann-Kendall test, linear regression model and joinpoint regression were used. Results Although erratic changes were observed in the median semen parameters (sperm concentration 40.1–52.1 × 106/ml, total sperm count 117.8–153.1 × 106, sperm progressive motility 33.4–38.1%) during the 7 years of observation, no significant decrease in semen quality was found, and 47.88% of infertile men showed normal semen parameters according to the World Health Organization (WHO) criteria. According to the joinpoint regression analysis, sperm progressive motility appeared to decrease earlier than the sperm concentration and total sperm count (at 28, 58, and 42 years of age, respectively). Conclusions There is no evidence of a deterioration in semen quality among infertile men in Hunan, China. Semen parameters decreased with increasing age, with turning points noted at different ages. Semen parameters are not absolute evidence for the assessment of male fertility potential. Therefore, we believe that, among semen parameters, the sperm concentration is the best predictor of fertility for ART, followed by motility. Decreased sperm motility may affect natural pregnancy, but it is not necessary for successful IVF.


2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Mary K. Samplaski ◽  
Trustin Domes ◽  
Keith A. Jarvi

Introduction. Chlamydia trachomatis is an established cause of tubal factor infertility; however its role in male fertility is not as clear. We sought to determine the prevalence of Chlamydia in infertile men and evaluate its impact on male reproductive potential. Materials and Methods. We compared the incidence of Chlamydia in our infertile male population with that reported in the literature. We then reviewed the impact of Chlamydia infection on male fertility. Results. The incidence of Chlamydia infection in our population of infertile men was 0.3%. There is considerable variability in the reported incidence, likely due to variation in the population studied, and detection technique. The optimal testing method and sample are presently unclear. The effect of Chlamydia on male reproductive function is also variable in the literature, but appears to be relatively minimal and may be related primarily to sperm DNA fragmentation or female partner transmission. Conclusions. The prevalence of Chlamydia in the infertile male population is low and routine testing is not supported by the literature. For high-risk infertile men, nucleic acid testing of urine +/− semen is the most sensitive method to detect Chlamydia. A validated testing system for semen needs to be developed, so that a standardized methodology can be recommended. In this way the full implications of Chlamydia on male fertility can be elucidated.


2013 ◽  
Vol 13 (1) ◽  
pp. 1-5 ◽  
Author(s):  
Richard Hampl ◽  
Jana Kubátová ◽  
Vladimír Sobotka ◽  
Jiří Heráček

AbstractThe data on hormonal steroids in the human seminal plasma and their role in spermatogenesis are summarized. The seminal steroid levels need not correlate with the blood plasma levels. The recent reports showed that androgen, especially dihydrotestosterone, and the estrogen levels in the seminal fluid may be used as the markers of spermatogenesis impairment. The estradiol concentration in the seminal plasma was higher than in the blood plasma, and its levels were significantly increased in men with impaired spermatogenesis. A good indicator for predicting the normal spermatogenesis, therefore, seems to be the testosterone/estradiol ratio. The seminal plasma also contains significant amounts of cortisol, which influences the androgen biosynthesis through its receptors in the Leydig cells. The local balance between cortisol and inactive cortisone is regulated by 11β-hydroxysteroid dehydrogenase, the activity of which may be affected by the environmental chemicals acting as the endocrine disruptors (EDCs). These compounds are believed to participate in worsening the semen quality – the sperm count, motility, and morphology, as witnessed in the recent last decades. As to the steroids’ role in the testis, the EDCs may act as antiandrogens by inhibiting the enzymes of testosterone biosynthesis, as the agonists or antagonists through their interaction with the steroid hormone receptors, or at the hypothalamic-pituitary-gonadal axis. Surprisingly, though the EDCs affect the steroid action in the testis, there is no report of a direct association between the concentrations of steroids and the EDCs in the seminal fluid. Therefore, measuring the steroids in the semen, along with the various EDCs, could help us better understand the role of the EDCs in the male reproduction.


2021 ◽  
Vol 12 (4) ◽  
pp. 2308-2315
Author(s):  
Rachid Mosbah ◽  
Aziez Chettoum ◽  
Alberto Mantovani

Selective serotonin reuptake inhibitors (SSRI) are a class of molecules used in treating depression, anxiety, and mood disorders. Paroxetine (PRT) is one of the most prescribed antidepressants, which has attracted great attention regarding its side effects in recent years.  This study was planned to assess the adverse effects of paroxetine on the biochemical parameters and reproductive system. Fourteen male Wistar rats were randomly allocated into two groups (7 rats for each): control and treated with paroxetine at a dose of 5mg/kg.bw for two weeks. At the end of the experiment, blood was collected from the retro-orbital plexus for measuring the biochemical parameters, whereas the reproductive organs were removed for measuring semen quality and the histological investigations. Results showed that paroxetine induced significant changes in some biochemical parameters and alteration of semen quality, including sperm count, spermatids number and sperm viability, motility and abnormalities. The histopathological examinations of testis and epididymis revealed an alteration of spermatogenesis, cellular disorganization and vacuolization, enlargement of interstitial space, shrinkage and degenerative changes in the epithelium of seminiferous and epididymal tubules with few to nil numbers of spermatozoa in their lumen. In conclusion, paroxetine treatment caused changes in some biochemical parameters and sperm profiles as well as histopathologic effects of reproductive organs.


2021 ◽  
Vol 48 (2) ◽  
pp. 97-104
Author(s):  
Ahmed T. Alahmar ◽  
Aldo E. Calogero ◽  
Rajender Singh ◽  
Rossella Cannarella ◽  
Pallav Sengupta ◽  
...  

Male infertility has a complex etiopathology, which mostly remains elusive. Although research has claimed that oxidative stress (OS) is the most likely underlying mechanism of idiopathic male infertility, the specific treatment of OS-mediated male infertility requires further investigation. Coenzyme Q10 (CoQ10), a vitamin-like substance, has been found in measurable levels in human semen. It exhibits essential metabolic and antioxidant functions, as well as playing a vital role in mitochondrial bioenergetics. Thus, CoQ10 may be a key player in the maintenance of biological redox balance. CoQ10 concentrations in seminal plasma directly correlate with semen parameters, especially sperm count and sperm motility. Seminal CoQ10 concentrations have been shown to be altered in various male infertility states, such as varicocele, asthenozoospermia, and medical or surgical regimens used to treat male infertility. These observations imply that CoQ10 plays an important physiological role in the maintenance and amelioration of semen quality. The present article thereby aimed to review the possible mechanisms through which CoQ10 plays a role in the regulation of male reproductive function, and to concisely discuss its efficacy as an ameliorative agent in restoring semen parameters in male infertility, as well as its impact on OS markers, sperm DNA fragmentation, pregnancy, and assisted reproductive technology outcomes.


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.


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