scholarly journals MiR-125b-2 Knockout in Testis Is Associated with Targeting to the PAP Gene, Mitochondrial Copy Number, and Impaired Sperm Quality

2019 ◽  
Vol 20 (1) ◽  
pp. 148 ◽  
Author(s):  
Longlong Li ◽  
Yanling Zhu ◽  
Ting Chen ◽  
Jiajie Sun ◽  
Junyi Luo ◽  
...  

It has been reported that the miR-125 family plays an important role in regulating embryo development. However, the function of miR-125b-2 in spermatogenesis remains unknown. In this study, we used a model of miR-125b knockout (KO) mice to study the relationship between miR-125b-2 and spermatogenesis. Among the KO mice, the progeny test showed that the litter size decreased significantly (p = 0.0002) and the rate of non-parous females increased significantly from 10% to 38%. At the same time, the testosterone concentration increased significantly (p = 0.007), with a remarkable decrease for estradiol (p = 0.02). Moreover, the sperm count decreased obviously (p = 0.011) and the percentage of abnormal sperm increased significantly (p = 0.0002). The testicular transcriptome sequencing revealed that there were 173 up-regulated genes, including Papolb (PAP), and 151 down-regulated genes in KO mice compared with wild type (WT). The Kyoto Encyclopedia of Genes and Genomes (KEGG) and gene ontology (GO) analysis showed that many of these genes were involved in sperm mitochondrial metabolism and other cellular biological processes. Meanwhile, the sperm mitochondria DNA (mtDNA) copy number increased significantly in the KO mice, but there were no changes observed in the mtDNA integrity and mutations of mt-Cytb, as well as the mt-ATP6 between the WT mice and KO mice. In the top 10 up-regulated genes, PAP, as a testis specific expressing gene, affect the process of spermatogenesis. Western blotting and the Luciferase assay validated that PAP was the target of miR-125b-5p. Intriguingly, we also found that both miR-125b and PAP were only highly expressed in the germ cells (GC) instead of in the Leydig cells (LC) and Sertoli cells (SC). Additionally, miR-125b-5p down regulated the secretion of testosterone in the TM3 cell by targeting PAP (p = 0.021). Our study firstly demonstrated that miR-125b-2 regulated testosterone secretion by directly targeting PAP, and increased the sperm mtDNA copy number to affect semen quality. The study indicated that miR-125b-2 had a positive influence on the reproductive performance of animals by regulating the expression of the PAP gene, and could be a potential drugs and diagnostic target for male infertility.

Author(s):  
Longlong Li ◽  
Yanling Zhu ◽  
Jiajie Sun ◽  
Ting Chen ◽  
Junyi Luo ◽  
...  

microRNAs can cause male infertility by impacting sperm quality and impaired spermatogenesis. Since the miR-125 family plays an important role in regulating embryo development, but the function of miR-125b-2 in male reproduction remains unknown. In this study, we prepared a model of miR-125b knockout (KO) mice. Among the KO mice, the progeny test showed that litter sizes decreased significantly and the rate of non-parous females increased significantly (p<0.05). At the same time, the testosterone concentration increased significantly (p<0.01), with the remarkable decrease for estradiol (p<0.05). Moreover, sperm count decreased obviously (p<0.05) and the percentage of abnormal sperms increased significantly (p<0.01). Testicular transcriptome sequencing demonstrated that there were 173 up-regulated genes, including Papolb (PAP), and 151 down-regulated genes in KO mice compared with wild type (WT). KEGG and GO analysis showed many of these genes were involved in sperm mitochondrial metabolism and other cellular biological processes. Meanwhile, the sperm mitochondria DNA (mtDNA) copy number was increased significantly (p<0.01) in KO mice, but the integrity of mtDNA and nuclear DNA (nDNA) had no change. In the top 10 up-regulated genes, as a testis specific expressing gene, PAP can affect the process of spermatogenesis. Western blotting and Luciferase Assay validated that PAP was the target of miR-125b-5p. Intriguingly, we also found that both miR-125b and PAP were only highly expressed in germ cells (GC) instead of Leydig cells (LC) and Sertoli cells (SC), and miR-125b-5p could target PAP to regulate TM3 cell secretion of testosterone (p<0.05). Our study firstly demonstrated that miR-125b-2 could regulate testosterone secretion by directly targeting PAP and increase sperm mtDNA copy number to affect semen quality. The study indicated that miR-125b-2 had a positive influence on the reproductive performance of animal and could be a potential therapeutic target for male infertility.


Reproduction ◽  
2013 ◽  
Vol 145 (3) ◽  
pp. 227-235 ◽  
Author(s):  
M Cambi ◽  
L Tamburrino ◽  
S Marchiani ◽  
B Olivito ◽  
C Azzari ◽  
...  

Oxidative stress (OS) is involved in many disoders including male infertility. Human spermatozoa are very sensitive targets of reactive oxygen species (ROS) and most sperm functions are impaired in the case of OS. In addition unbalanced production of ROS is considered one of the most important causes of sperm DNA fragmentation, a semen trait of infertile men. The relationship between oxidative damage and semen quality is partially controversial, probably due to the different methods and/or targets used to reveal the OS. In this study, by fluorescence microscopy and flow cytometry, we compared two methods to reveal 8-hydroxy,2-deoxyguanosine (8-OHdG), the hallmark of oxidative DNA damage: an immunofluorescence method and the commercial OxyDNA kit. We found that although both methods localized the labelling in sperm nuclei they yielded different measures, and only with the immunofluorescence method was the labelling specific for sperm 8-OHdG. The immunofluorescence method, coupled to flow cytometry, was thus selected to analyse the 8-OHdG content in semen samples from 94 subfertile patients and to investigate the relationship with semen quality. We found that the percentages of spermatozoa with 8-OHdG (mean±s.d., 11.4±6.9%) were related to sperm count (Pearson's correlation coefficient (r)=−0.27, P=0.04 (ANOVA and student's t-test)), motility (progressive: r=−0.22, P=0.04; non-progressive: r=0.25, P=0.01), and normal morphology (r=−0.27, P=0.01). In conclusion, we demonstrate that immunofluorescence/flow cytometry is a reliable and specific method to detect 8-OHdG at single-cell level and show that oxidative damage only partially overlaps poor semen quality, suggesting that it could provide additional information on male fertility with respect to routine semen analysis.


2020 ◽  
Vol 14 (3) ◽  
pp. 155798832092598
Author(s):  
Nathan L. McCray ◽  
Heather A. Young ◽  
Michael S. Irwig ◽  
David Frankfurter ◽  
Arnold M. Schwartz ◽  
...  

A decades-long decline in sperm counts in Western countries has coincided with an increase in obesity rates, prompting study into their association. Few of these studies have incorporated men of color, the sperm health of whom is relatively unknown. The present exploratory study evaluated the association between body mass index (BMI), race, ethnicity, and sperm parameters among a diverse sample of U.S. men attending a Washington, DC physician practice. Semen samples were collected and processed at a single laboratory and sperm concentration, motility, morphology, and count were evaluated according to World Health Organization (WHO) 5th edition criteria. Multivariate models accounted for covariates related to sperm health. The study population ( n = 128) was largely obese (45.3%) or overweight (34.4%), and 36.0% were black or Hispanic. Black men had lower adjusted sperm concentration compared to white men (75.0 million/mL to 107.4 million/mL, p = .01) and were more likely to have oligozoospermia ( p = .01), asthenozoospermia ( p = .004), and low sperm count ( p < .0001). Hispanic men had higher adjusted sperm concentration compared to non-Hispanic men (124.5 million/mL to 62.1 million/mL, p = .007) and were less likely to have teratozoospermia ( p = .001). Obesity and BMI were associated with lower sperm motility and count in crude models only. Given the study’s sample size its findings should be interpreted with caution but align with the limited epidemiological literature to date that has evaluated racial and ethnic differences in semen quality. Heightened clinical research attention is needed to ensure men of color are included in representative numbers in studies of urologic and andrologic health.


Author(s):  
Mikkel Fode ◽  
Jens Sønksen

While spinal cord injury (SCI) does not affect female fertility, the condition most often results in infertility in males due to anejaculation and reduced semen quality. Anejaculation is caused by disruption of the autonomic nerve fibres, which are normally responsible for the ejaculation. The reason for the poor sperm quality has not been firmly established. If spinal cord injured men cannot ejaculate by sexual intercourse or masturbation, ejaculation can be induced by either penile vibratory stimulation or electroejaculation. Only if these methods fail should surgical sperm retrieval be considered. The method of insemination depends largely on the total motile sperm count and patient preference. With the right treatment, it is possible for most SCI men to have children.


2019 ◽  
Vol 22 (10) ◽  
pp. 882-889 ◽  
Author(s):  
María F García ◽  
Romina Nuñez Favre ◽  
María C Stornelli ◽  
Ramiro Rearte ◽  
María C García Mitacek ◽  
...  

Objectives The current study aimed to evaluate the relationship between specific seminal plasma components – cholesterol (CHOL), triacylglycerols (TAG) and total protein (PROT) concentrations – and semen quality in cats. A further aim was to determine the relationship between specific seminal protein bands and semen quality. Methods Thirteen toms, 2–5 years of age, were included. Semen collection was performed by electroejaculation every 4 weeks. Fifty-eight ejaculates were assessed for motility, velocity, volume, sperm concentration, total sperm count, viability, acrosome integrity, plasma membrane integrity and sperm morphology. Samples were divided into two groups: good semen quality (GSQ) and poor semen quality (PSQ). After evaluation, seminal plasma was separated from the sperm by centrifugation and stored at −20°C. CHOL, TAG and PROT concentrations were then assessed and seminal plasma protein profile was determined by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). Results Seminal plasma CHOL and TAG concentrations, motility, velocity, sperm concentration, total sperm count and sperm morphology were significantly higher in GSQ cats compared with PSQ cats ( P <0.01). Moreover, seminal plasma SDS-PAGE analysis showed an identifiable extra band exclusively in the GSQ group. Conclusions and relevance Data obtained in this study showed that seminal plasma CHOL and TAG concentrations and specific protein bands could be used to improve semen evaluation in toms. In this sense, the 14 kDa protein band could be a valuable marker for semen quality in the cat and should be further investigated. However, more studies are necessary to determine its relationship with fertility.


2018 ◽  
Vol 58 (9) ◽  
pp. 1608
Author(s):  
T. L. B. G. Lins ◽  
V. G. Menezes ◽  
R. S. Barberino ◽  
S. A. P. Costa ◽  
N. M. S. S. Santos ◽  
...  

The aim of the present study was to evaluate the influence of water salinity on semen quality, and on the morphology and apoptosis of germinal epithelial cells in prepubertal Morada Nova male lambs. Thirty-two lambs were allocated into four treatments with different amounts of sodium chloride (NaCl) added to the drinking water to simulate different water salinities; consequently, the concentrations of total dissolved solids (TDS) were as follows: 640 (control), 3188; 5740 and 8326 mg/L TDS. After 78 days, sperm was collected for analysis. The animals were slaughtered and histological and morphometric analyses and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling (TUNEL) assay were performed on the testis tissue. The thickness of the germinal epithelium and diameter of the seminiferous tubules were measured. A quadratic effect (P < 0.05) was observed in regard to semen volume and sperm abnormalities. There was an increase in the sperm count in the treatment containing 3188 mg/L TDS, compared with the control (640 mg/L TDS); however, this treatment did not differ (P > 0.05) from the other salinity treatments. Moreover, treatments with 3188 mg/L or 5740 mg/L TDS showed a higher (P < 0.05) spermatic vigour than did the other treatments. There was an increase (P < 0.05) in the number of TUNEL-positive cells in the treatment with the highest salinity (8326 mg/L TDS) compared with the control and other treatments. In conclusion, water used for drinking should contain between 3188 and 5740 mg/mL TDS so as to improve the concentration, vigour, motility and volume of semen, and to decrease sperm abnormalities in germinal cells of seminiferous tubule of Morada Nova ram lambs.


2020 ◽  
Vol 11 (3) ◽  
pp. 4068-4073
Author(s):  
Kanimozhi S ◽  
Bupesh G ◽  
Sumathy G ◽  
Jeganath S

Numerous examinations have announced that the Nicotine present in tobacco smoke adverse affects sperm parameters, fundamental plasma, and different other richness factors. These harms are because of the natural finding that smoking expands the degree of free radicals, consequently bringing about oxidative pressure. Accordingly, an increment of free radicals, DNA harm and lipid peroxidation in human sperm may happen to bring about impedance of sperm quality. nicotine organization in trial creatures was initiate to influence spermatogenesis, epididymal sperm count, motility and treating capability of sperms. Huge quantities of restorative herbs have been recorded in siddha framework that improve spermatogenesis and increment the nature of sperm. The present review gives an outline on the relationship between male richness incited by nicotine and defensive impacts of different natural plants on it. The paper additionally features the dynamic, common standards, and rough concentrates of plants, which have been valuable in improving nicotine instigated testicular harms and supportive in spermatogenesis and multiplication. Despite the fact that the discoveries of this survey propose numerous herbs are extremely viable against nicotine actuated male barrenness still increasingly clinical preliminaries are prescribed to show their viability on nicotine instigated male infertility


2021 ◽  
Author(s):  
Min Xie ◽  
Silvan Hämmerli ◽  
Kerstin Blickenstorfer ◽  
Brigitte Leeners

Abstract Purpose: The length of sexual abstinence seems to influence sperm quality. However, few data on the relevance of abstinence time in pathological sperm samples are available. With our study, we look for associations of abstinence length and semen quality. Methods: We studied semen samples from 4423 men undergoing fertility evaluation. Sperm concentration, percentage of progressively motile spermatozoa, total motile sperm count, percentage of spermatozoa with normal morphology, were compared after each day and 0-2, 3-7 and >7 days of abstinence. Results: We found that a longer abstinence time was related to higher sperm concentration in normal semen samples (P<0.001) and in semen samples with any sperm pathology (P<0.001, P=0.004) with the exception of oligozoospermia (P=0.125). Longer abstinence time was also associated with significantly reduced progressive motility in normal samples (P<0.001) and in cases of teratozoospermia (P<0.001). In normal samples a higher percentage of sperm were morphologically normal after a shorter abstinence period (P=0.03); in oligoasthenoteratozoospermia (OAT) samples, this was the case after a longer abstinence period (P=0.013). Conclusion: A longer abstinence time is associated with higher sperm concentration, whereas sperm motility is optimal after shorter abstinence times; results on morphology are controversial. The recommendation on abstinence time needs to be adjusted in relation to the parameter that needs to be improved.


PLoS ONE ◽  
2020 ◽  
Vol 15 (11) ◽  
pp. e0242364
Author(s):  
Maxwell P. Cocco ◽  
Evan White ◽  
Shujie Xiao ◽  
Donglei Hu ◽  
Angel Mak ◽  
...  

Background Mitochondria support critical cellular functions, such as energy production through oxidative phosphorylation, regulation of reactive oxygen species, apoptosis, and calcium homeostasis. Objective Given the heightened level of cellular activity in patients with asthma, we sought to determine whether mitochondrial DNA (mtDNA) copy number measured in peripheral blood differed between individuals with and without asthma. Methods Whole genome sequence data was generated as part of the Trans-Omics for Precision Medicine (TOPMed) Program on participants from the Study of Asthma Phenotypes and Pharmacogenomic Interactions by Race-ethnicity (SAPPHIRE) and the Study of African Americans, Asthma, Genes, & Environment II (SAGE II). We restricted our analysis to individuals who self-identified as African American (3,651 asthma cases and 1,344 controls). Mitochondrial copy number was estimated using the sequencing read depth ratio for the mitochondrial and nuclear genomes. Respiratory complex expression was assessed using RNA-sequencing. Results Average mitochondrial copy number was significantly higher among individuals with asthma when compared with controls (SAPPHIRE: 218.60 vs. 200.47, P<0.001; SAGE II: 235.99 vs. 223.07, P<0.001). Asthma status was significantly associated with mitochondrial copy number after accounting for potential explanatory variables, such as participant age, sex, leukocyte counts, and mitochondrial haplogroup. Despite the consistent relationship between asthma status and mitochondrial copy number, the latter was not associated with time-to-exacerbation or patient-reported asthma control. Mitochondrial respiratory complex gene expression was disproportionately lower in individuals with asthma when compared with individuals without asthma and other protein-encoding genes. Conclusions We observed a robust association between asthma and higher mitochondrial copy number. Asthma having an effect on mitochondria function was also supported by lower respiratory complex gene expression in this group.


2020 ◽  
Vol 2020 ◽  
pp. 1-7
Author(s):  
Richard Michael Blay ◽  
Abigail Duah Pinamang ◽  
Augustine E. Sagoe ◽  
Ewurama Dedea Ampadu Owusu ◽  
Nii Koney-Kwaku Koney ◽  
...  

Introduction. Male infertility is known to contribute about half of all infertility cases. In Ghana, the prevalence of male infertility is higher (15.8%) than in females (11.8%). Sperm quality is associated with the likelihood of pregnancy and known to be the cause of male fertility problems 90% of the time. Exposure to certain environmental factors reduces semen quality in men. The study examined the effects of environmental and lifestyle factors on semen quality in Ghanaian men. Materials and Methods. This was a cross-sectional study involving 80 apparent healthy adult males in their reproductive age. Participants were males referred to the laboratory (Immunology Unit of the Korle-Bu Teaching Hospital) for semen analysis test and/or culture and sensitivity. Participants were made to fill out a questionnaire which entailed selected environmental factors (accidents or trauma, exposure to chemicals, radiation, and heat) and lifestyle habits (including alcohol consumption, smoking, and whether participants sat more or less than 4 hours per day). Semen samples were then collected by masturbation into sterile containers and analysed in accordance with WHO guidance for semen analysis within 60 minutes after ejaculation and collection. Results. About 69% of participants had semen pH within the normal range compared to 15% whose pH were lower than 7.2. There was a significantly high number of immotile sperm cells ( p value = 0.017) in participants who sat for more than 4 hours as compared to those that sat for less than 4 hours in a day. Active sperm motility and viability showed significant increase ( p value = 0.002 and 0.009, respectively) in participants who kept their cell phones in their side pockets. Smoking produced a twofold decrease in sperm count as smokers had a significantly lower sperm count ( 12.28 ± 10.95 × 10 6 /ml) compared to the smoke-free ( 23.85 ± 22.14 × 10 6 /ml). For exposure to STDs, no significant differences were recorded among study groups concerning semen quality. Conclusion. Sperm quality in Ghanaian men is associated with lifestyle habits. Smoking and sitting for long hours influenced sperm motility and count, respectively. Knowledge of the factors that influence sperm quality in this geographical region can contribute to informed decisions on effective management of infertility in Ghanaian men.


Sign in / Sign up

Export Citation Format

Share Document