scholarly journals The Tug1 Locus is Essential for Male Fertility

2019 ◽  
Author(s):  
Jordan P. Lewandowski ◽  
Gabrijela Dumbović ◽  
Audrey R. Watson ◽  
Taeyoung Hwang ◽  
Emily Jacobs-Palmer ◽  
...  

ABSTRACTBackgroundSeveral long noncoding RNAs (lncRNAs) have been shown to function as central components of molecular machines that play fundamental roles in biology. While the number of annotated lncRNAs in mammalian genomes has greatly expanded, their functions remain largely uncharacterized. This is compounded by the fact that identifying lncRNA loci that have robust and reproducible phenotypes when mutated has been a challenge.ResultsWe previously generated a cohort of 20 lncRNA loci knockout mice. Here, we extend our initial study and provide a more detailed analysis of the highly conserved lncRNA locus, Taurine Upregulated Gene 1 (Tug1). We report that Tug1 knockout male mice are sterile with complete penetrance due to a low sperm count and abnormal sperm morphology. Having identified a lncRNA loci with a robust phenotype, we wanted to determine which, if any, potential elements contained in the Tug1 genomic region (DNA, RNA, protein, or the act of transcription) have activity. Using engineered mouse models and cell-based assays, we provide evidence that the Tug1 locus harbors three distinct regulatory activities – two noncoding and one coding: (i) a cis DNA repressor that regulates many neighboring genes, (ii) a lncRNA that can regulate genes by a trans-based function, and finally (iii) Tug1 encodes an evolutionary conserved peptide that when overexpressed impacts mitochondrial membrane potential.ConclusionsOur results reveal an essential role for the Tug1 locus in male fertility and uncover three distinct regulatory activities in the Tug1 locus, thus highlighting the complexity present at lncRNA loci.

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ewa Janiszewska ◽  
Izabela Kokot ◽  
Iwona Gilowska ◽  
Ricardo Faundez ◽  
Ewa Maria Kratz

AbstractIn the seminal plasma (n = 118) and serum (n = 90) clusterin (CLU) the fucosylation and the expression of selected fucosyltransferases (FUTs) were analyzed. Samples from infertile men were divided into groups based on the results of the standard semen analysis: normozoospermic (N), teratozoospermic (T), asthenoteratozoospermic (AT) and oligoasthenoteratozoospermic (OAT). The CLU fucosylation was analyzed using lectin-ELISAs with biotinylated lectins specific to α1,3-, α1,2-linked antennary fucose, and α1,6-linked core fucose (LTA, UEA, and LCA, respectively). The concentrations of FUT3 and FUT4, reflecting the expression of Le oligosaccharide structures, were measured using ELISA tests. The differences in serum CLU and FUT4 concentrations, and in the expression of core fucose and antennary fucose α1,2-linked in CLU glycans between the N group and other groups examined suggest that the disturbances in sperm count, motility, and morphology are not the only cause of male infertility. Lack of similarities between levels of examined parameters in blood serum and seminal plasma may suggest the differences in mechanisms leading to glycoproteins glycosylation. It confirmed the observed differences in concentrations of seminal plasma CLU, FUT3, and FUT4 between the OAT group and N, T, AT groups, indicating that decreased sperm count may be related to these parameters expression. The serum CLU concentrations and expression of core fucose and fucose α1,2-linked in CLU, seem to be good markers differentiating normozoospermic men from those with abnormal sperm parameters, which was not observed for seminal plasma.


2020 ◽  
Vol 34 (12) ◽  
pp. 16224-16242
Author(s):  
Yoichi Miyamoto ◽  
Mitsuho Sasaki ◽  
Haruhiko Miyata ◽  
Yoko Monobe ◽  
Masahiro Nagai ◽  
...  

AYUSHDHARA ◽  
2021 ◽  
pp. 3566-3573
Author(s):  
Nagendra Chary.M ◽  
Lalitha B.R ◽  
T.Anil Kumar

Male reproductive health depends upon the normal structures and functions of Shukrava srotas. Shukra is composed of both sperm and semen and considered one of the important factors for fertilization. It is stated as Phalavat shukra. Preceptors of Ayurveda have described eight types of Shukra dosha and their treatments. Low sperm count, decrease sperm motility, abnormal sperm morphology, ejaculatory problems, sexual dysfunctions, environmental exposures (radiation, pollution, and stress etc), lifestyle habits (smoking, alcohol, recreational drugs etc), varicocele, hormonal imbalances, DNA damage, and reactive oxygen species (ROS) etc are causative factors for Male infertility. Thousands of years back, ancient system of medicine has mentioned the word Purusha vandya (male infertility) and different pharmacological activities, medicinal formulas, therapies to treat sperm disorders, semen impairments, and sexual dysfunctions. Vajeekarana is one of the special branches of Astanga Ayurveda which maintains the fertility and management of male infertility. Shukrala, Shukra janana, Shukra shodhana, Shukra rechaka, Shukra pravataka and Shukra sthambhaka etc., are the pharmacological activities mentioned to treat Shukradoshas. Shukrala karma mainly composed of Shukra vrudhikara and Shukra srutikara means which enhances the Shukra (semen and sperm) quantitatively and qualitatively and facilitates its ejaculation. Therefore, an attempt has been made to establish the concept of Shukrala karma and its therapeutic applicability in the management of male infertility.


Author(s):  
Meltem Mermer ◽  
Yasemin Akdevelioğlu

Obesity causes many health problems as well as having negative effects on fertility. There is a multifaceted relationship between obesity and male infertility. Male fertility is associated with sperm concentration, motility and morphology. Testosterone (total and free) and gonadotropin levels were low and estrogen levels were found to be high in obese men. The decrease in androgen levels varies based on the degree of obesity. High body mass index is inversely related to total sperm count, sperm concentration, sperm morphology and number of motile sperm. Leptin and ghrelin are hormones that influence body weight regulation and eating behaviors. Serum leptin level, which is high in obese infertile men, showed a significant positive correlation with abnormal sperm morphology, serum FSH, LH, prolactin level and showed a significant negative correlation with sperm concentration, sperm motility and serum testosterone level. Further research is needed on the effects of ghrelin levels on male infertility. The relationship between obesity and erectile dysfunction can be explained by decreased testosterone levels and elevation of some proinflammatory cytokine levels. Decreased physical activity due to obesity, long-term sitting increases testicular temperature and affects sperm production negatively. There is a multifaceted relationship between obesity, metabolic syndrome and type 2 diabetes and serum testosterone and SHBG. Diet and exercise showed improvement in testosterone levels and sperm concentration due to decreased body weight. However, studies on this subject are extremely limited. The possible effects of weight loss on successful infertility treatment of obese men should not be ignored.


1980 ◽  
Vol 95 (2) ◽  
pp. 251-257 ◽  
Author(s):  
Marie Føgh ◽  
Charles S. Corker ◽  
Helen McLean ◽  
William M. Hunter ◽  
Ivan Bruunshuus Petersen ◽  
...  

Abstract. Two groups of six men took levo-norgestrel (250 or 500 μg daily) by mouth and testosterone oenanthate (200 mg monthly, intramuscurlarly) for six months. A three months placebo period preceded the medication which was followed by a recovery phase of 6–10 months. Two volunteers withdrew due to side effects. The five men taking the low doses of levo-norgestrel (250 μg) exhibited a reduction in sperm count, but not to azoospermia. The high dose of levo-norgestrel (500 μg) was more effective, sperm count was reduced to < 6 × 106/ ml in 3 of 5 volunteers and to < 17 × 106/ml in the remainder. s-Testosterone, LH and FSH were decreased by the treatment. The men had no toxicological side effects or changes in libido and potency. During the recovery period sperm counts, sperm morphology, s-testosterone, LH and FSH returned to normal levels.


2016 ◽  
Vol 6 (12) ◽  
pp. 990-993
Author(s):  
AK Chaurasia ◽  
AK Sinha ◽  
P Upahdyay

Background: Semen analysis is used to evaluate male fertility. The aim of this study was to compare the results of semen analysis using manual method and automated sperm analyzer.Materials and Methods: This was a comparative study of 50 cases of semen analysis done in the Department of Pathology at the B.P. Koirala Institute of Health Sciences from March 2009 to March 2010. The automated sperm analyzer did not show the WHO parameters of patients who had functional sperm count (FSC) less than five hundred thousand (500,000). Semen analysis of each of the case included in the study was done by manual and automated method (using SQAII-P analyzer).Results: Out of 31 patients, the mean age of the patients was 28.56 years with youngest patient of 20 years and eldest of 45 year. Sensitivity and specificity was 100% in analysis of sperm concentration by both the methods. Sperm motility analysis showed 100% sensitivity and 81.81% specificity. Sperm morphology analysis showed 100% sensitivity and 34.48% specificity.Conclusion: It was observed that the automated method is much quicker and precise than the conventional, manual method for semen analysis.


2012 ◽  
Vol 153 (45) ◽  
pp. 1787-1792 ◽  
Author(s):  
Mária Horváth ◽  
Endre Czeizel

Introduction: There is a decline in male fertility thus new treatments are needed. Aims: To test the efficacy of a new dietary supplement developed in the USA and registered as a curing drug in Hungary (OGYI). Methods: In a clinical trial 100 men with low sperm quality (spermium count 5–20 M/ml, good motility 10–40%, and adverse shape 30–50%) were examined. Results: Sperm parameters were measured before and after a 3-month treatment and after another 3-month without treatment. This dietary supplement statistically and clinically significantly improved sperm count and motility. In 74 cases this dietary supplement demonstrated a beneficial effect on sperm quality (more than 10% increase in sperm count, or quality of motility, or shape); in 16 cases the improvement exceeded 30%. No adverse effect could be accounted for this treatment. Conclusions: This new dietary supplement may contribute to the treatment of male infertility. Orv. Hetil., 2012, 153, 1787–1792.


Author(s):  
Thea Emily Benson ◽  
Anne Gaml-Sørensen ◽  
Andreas Ernst ◽  
Nis Brix ◽  
Karin Sørig Hougaard ◽  
...  

Bisphenol A (BPA) is considered an endocrine disruptor and has been associated with deleterious effects on spermatogenesis and male fertility. Bisphenol F (BPF) and S (BPS) are structurally similar to BPA, but knowledge of their effects on male fertility remains limited. In this cross–sectional study, we investigated the associations between exposure to BPA, BPF, and BPS and semen quality in 556 men 18–20 years of age from the Fetal Programming of Semen Quality (FEPOS) cohort. A urine sample was collected from each participant for determination of BPA, BPF, and BPS concentrations while a semen sample was collected to determine ejaculate volume, sperm concentration, total sperm count, sperm motility, and sperm morphology. Associations between urinary bisphenol levels (continuous and quartile–divided) and semen characteristics were estimated using a negative binomial regression model adjusting for urine creatinine concentration, alcohol intake, smoking status, body mass index (BMI), fever, sexual abstinence time, maternal pre–pregnancy BMI, and first trimester smoking, and highest parental education during first trimester. We found no associations between urinary bisphenol of semen quality in a sample of young men from the general Danish population.


2013 ◽  
Vol 4 (2) ◽  
pp. 20-25
Author(s):  
ZU Naher ◽  
SK Biswas ◽  
FH Mollah ◽  
M Ali ◽  
MI Arslan

Infertility is a worldwide problem and in almost 50% of cases infertility results from abnormality of the male partners. Apart from endocrine disorders, definitive cause and mechanism of male infertility is not clear in many cases. Recent evidence indicates that imbalance between pro-oxidant stress and antioxidant defense plays an important role in the pathogenesis of male infertility. Among the endogenous antioxidant systems, reduced glutathione (GSH) plays a significant role in the antioxidant defense of the spermatogenic epithelium, the epididymis and perhaps in the ejaculated spermatozoa. The current study was therefore designed to evaluate any association that may exist between GSH levels and male infertility. Infertile male patients (having female partners with normal fertility parameters; n=31) and age- matched healthy male fertile control subjects (n=30) were included in this study. In addition to medical history, semen analyses including semen volume, sperm count, motility and morphology were done for each subject. As a measure of antioxidant capacity erythrocyte and seminal plasma GSH concentrations were measured by Ellman's method in fertile and infertile male subjects. The infertile subjects were similar to fertile subjects in terms of age. However, semen volume and sperm count was found significantly lower (p<0.001) in infertile males compared with healthy fertile male subjects. Percentage of subjects with abnormal sperm morphology and motility were found higher in infertile group compared with fertile group. The median (range) erythrocyte GSH level did not differ between the two groups (12.62 (0.67-29.82) versus 13.93 (2.10-21.08) mg/gm Hb). However, the seminal plasma GSH level was found markedly suppressed in infertile group (1.64 (0.23-7.50)) compared with fertile group (4.26 (2.32-7.50)) mg/dl (p<0.001). In the present study seminal plasma GSH level was found markedly suppressed along with abnormal values for semen volume, sperm concentration and sperm morphology and motility in infertile subjects compared with fertile subjects. This finding indicates that low level of seminal plasma GSH level may be associated with male infertility. DOI: http://dx.doi.org/10.3329/bjmb.v4i2.13772 Bangladesh J Med Biochem 2011; 4(2): 20-25


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