Gene expression linked to male infertility

2012 ◽  
Author(s):  
Moheb Costandi
Keyword(s):  
Gene Expression ◽  
Male Infertility

The Protective Effect of Metformin against Oxandrolone-Induced Infertility in Male Rats

2020 ◽  
Vol 26 ◽  
Author(s):  
Abdulqader Fadhil Abed ◽  
Yazun Bashir Jarrar ◽  
Hamzeh J Al-Ameer ◽  
Wajdy Al-Awaida ◽  
Su-Jun Lee
Keyword(s):  
Gene Expression ◽  
Male Infertility ◽  
Protective Effect ◽  
Histological Examination ◽  
Sperm Count ◽  
Serum Testosterone ◽  
Male Rats ◽  
P Value ◽  
Protective Effects ◽  
Rt Pcr

Background: Oxandrolone is a synthetic testosterone analogue that is widely used among bodybuilders and athletes. However, oxandrolone causes male infertility. Recently, it was found that metformin reduces the risk of infertility associated with diabetes mellitus. Aim: This study aimed to investigate the protective effects of metformin against oxandrolone-induced infertility in male rats. Methods: Rats continuously received one of four treatments (n=7) over 14 days: control DMSO administration, oxandrolone administration, metformin administration, or co-administration of oxandrolone and metformin. Doses were equivalent to those used for human treatment. Subsequently, testicular and blood samples were collected for morphological, biochemical, and histological examination. In addition, gene expression of the testosterone synthesizing enzyme CYP11A1 was analyzed in the testes using RT-PCR. Results: Oxandrolone administration induced male infertility by significantly reducing relative weights of testes by 48%, sperm count by 82%, and serum testosterone levels by 96% (ANOVA, P value < 0.05). In addition, histological examination determined that oxandrolone caused spermatogenic arrest which was associated with 2-fold downregulation of testicular CYP11A1 gene expression. However, co-administration of metformin with oxandrolone significantly ameliorated toxicological alterations induced by oxandrolone exposure (ANOVA, P value < 0.05). Conclusion: Metformin administration protected against oxandrolone-induced infertility in male rats. Further clinical studies are needed to confirm the protective effect of metformin against oxandrolone-induced infertility among athletes.

scholarly journals Epigenetics in Male Infertility

2021 ◽  
Author(s):  
Hayfa H. Hassani ◽  
Rakad M. Kh AL-Jumaily ◽  
Fadhel M. Lafta
Keyword(s):  
Gene Expression ◽  
Male Infertility ◽  
Medical Condition ◽  
Wide Spectrum ◽  
Regulatory Elements ◽  
Great Promise ◽  
Genomic Integrity ◽  
Idiopathic Male Infertility ◽  
Scientific Attention ◽  
Proteomic Research

Male infertility is a complex medical condition, in which epigenetic factors play an important role. Epigenetics has recently gained significant scientific attention since it has added a new dimension to genomic and proteomic research. As a mechanism for maintaining genomic integrity and controlling gene expression, epigenetic modifications hold a great promise in capturing the subtle, yet very important, regulatory elements that might drive normal and abnormal sperm functions. The sperm’s epigenome is known to be marked by constant changing over spermatogenesis, which is highly susceptible to be influenced by a wide spectrum of environmental stimuli. Recently, epigenetic aberrations have been recognized as one of the causes of idiopathic male infertility. Recent advances in technology have enabled humans to study epigenetics role in male infertility.

scholarly journals Molecular Profiling of Spermatozoa Reveals Correlations between Morphology and Gene Expression: A Novel Biomarker Panel for Male Infertility

2021 ◽  
Vol 2021 ◽  
pp. 1-14
Author(s):  
Nino Guy Cassuto ◽  
David Piquemal ◽  
Florence Boitrelle ◽  
Lionel Larue ◽  
Nathalie Lédée ◽  
...  
Keyword(s):  
Gene Expression ◽  
Male Infertility ◽  
Assisted Reproductive Technologies ◽  
Reproductive Technologies ◽  
Poor Quality ◽  
Semen Parameters ◽  
Functional Evaluation ◽  
Sperm Analysis ◽  
Biomarker Panel ◽  
Network Analyses

Choosing spermatozoa with an optimum fertilizing potential is one of the major challenges in assisted reproductive technologies (ART). This selection is mainly based on semen parameters, but the addition of molecular approaches could allow a more functional evaluation. To this aim, we used sixteen fresh sperm samples from patients undergoing ART for male infertility and classified them in the high- and poor-quality groups, on the basis of their morphology at high magnification. Then, using a DNA sequencing method, we analyzed the spermatozoa methylome to identify genes that were differentially methylated. By Gene Ontology and protein–protein interaction network analyses, we defined candidate genes mainly implicated in cell motility, calcium reabsorption, and signaling pathways as well as transmembrane transport. RT-qPCR of high- and poor-quality sperm samples allowed showing that the expression of some genes, such as AURKA, HDAC4, CFAP46, SPATA18, CACNA1C, CACNA1H, CARHSP1, CCDC60, DNAH2, and CDC88B, have different expression levels according to sperm morphology. In conclusion, the present study shows a strong correlation between morphology and gene expression in the spermatozoa and provides a biomarker panel for sperm analysis during ART and a new tool to explore male infertility.

scholarly journals Tsga8 is required for spermatid morphogenesis and male fertility in mice

Development ◽  
2021 ◽  
Vol 148 (8) ◽  
Author(s):  
Yuki Kobayashi ◽  
Shin-ichi Tomizawa ◽  
Michio Ono ◽  
Kazushige Kuroha ◽  
Keisuke Minamizawa ◽  
...  
Keyword(s):  
Gene Expression ◽  
Stem Cells ◽  
Male Infertility ◽  
Intracytoplasmic Sperm Injection ◽  
Male Fertility ◽  
Essential Role ◽  
Key Factors ◽  
Nuclear Condensation ◽  
Chromosomal Distribution ◽  
Epigenetic Modifiers

ABSTRACT During spermatogenesis, intricate gene expression is coordinately regulated by epigenetic modifiers, which are required for differentiation of spermatogonial stem cells (SSCs) contained among undifferentiated spermatogonia. We have previously found that KMT2B conveys H3K4me3 at bivalent and monovalent promoters in undifferentiated spermatogonia. Because these genes are expressed late in spermatogenesis or during embryogenesis, we expect that many of them are potentially programmed by KMT2B for future expression. Here, we show that one of the genes targeted by KMT2B, Tsga8, plays an essential role in spermatid morphogenesis. Loss of Tsga8 in mice leads to male infertility associated with abnormal chromosomal distribution in round spermatids, malformation of elongating spermatid heads and spermiation failure. Tsga8 depletion leads to dysregulation of thousands of genes, including the X-chromosome genes that are reactivated in spermatids, and insufficient nuclear condensation accompanied by reductions of TNP1 and PRM1, key factors for histone-to-protamine transition. Intracytoplasmic sperm injection (ICSI) of spermatids rescued the infertility phenotype, suggesting competency of the spermatid genome for fertilization. Thus, Tsga8 is a KMT2B target that is vitally necessary for spermiogenesis and fertility.

scholarly journals Identification of VASA Gene Expression in In-vitro Culture From Non-Obstructive Azoospermia (NOA) Testicular Biopsy Cells: A Study to Unlock Knowledge of Male Infertility

2018 ◽  
Vol 17 (2) ◽  
Author(s):  
Redzuan Abd Razak ◽  
Lokman Md Isa ◽  
Refaudeen Muhammad Razali ◽  
Afzan Mat Yusuf ◽  
Azantee Yazmie Abd Wahab ◽  
...  
Keyword(s):  
Gene Expression ◽  
Male Infertility ◽  
In Vitro Culture ◽  
Germ Line ◽  
Testicular Sperm Extraction ◽  
Obstructive Azoospermia ◽  
Psychological Issue ◽  
Healthy Man ◽  
Vasa Gene

The expression product of VASA gene is widely conserved germ line marker and participates to regulate the development of reproductive system and spermatogenesis in healthy man. Azoospermic is a condition which the man is unable to produce any sperm cells for reproduction activity. This condition produced has bad impact to the man since the ability to produce their own progeny will be interrupted or blocked forever. Not only the family bloodline of the man would be ended, the psychological issue like shamefulness and low self-esteem occurs. In Islam, seeking knowledge is an obligatory to Muslims in order to solve problems and improve lives. Thus to unveil the problem of azoospermic man we aimed to determine the level of VASA gene expression in samples of testes cells of non-obstructive azoospermic (NOA) and compare it with sperms of healthy man. Samples were taken from three NOA patients by testicular sperm extraction (TESE) to obtain testicular biopsies. Testicular cells were isolated and cultured in supplemented knockout DMEM media. VASA gene expression was determined by reverse transcriptase polymerase chain reaction (RT-PCR). The VASA gene expression from sperm of healthy man was also determined for comparison purpose. It was demonstrated that the addition of growth factor significantly increased SSC-like cells colony formation in tissues obtained from NOA patients. No VASA expression was detected in spermatogonial-like stem cells culture on day 1, 7, 14 and 21 in each of the azoospermic samples. Our findings shown VASA gene was not expressed in spermatogenesis in vitro culture that might be associated with the abnormal differentiation of primordial germ cells that lead to male infertility. Islam also teaches us to not have feelings of despair and for problems that we are facing but to find the solution and consider the problem as a test from the Almighty. All the tests should be handled with strong believe since only Allah (SWT) knows what the best for us and each of the tests will have justified wisdom and benefits which we as human being are unable to realise thoroughly.

The Role of Protamine 2 Gene Expression and Caspase 9 Activity in Male Infertility

2016 ◽  
Vol 195 (3) ◽  
pp. 796-800 ◽  
Author(s):  
Adel A. Zalata ◽  
Naglaa Mokhtar ◽  
Amany Atwa ◽  
Mohamed Khaled ◽  
Olfat G. Shaker
Keyword(s):  
Gene Expression ◽  
Male Infertility ◽  
Caspase 9 ◽  
Protamine 2

scholarly journals Correlation between the aberrant human testicular germ-cell gene expression and disruption of spermatogenesis leading to male infertility

2018 ◽  
Author(s):  
Arka Baksi ◽  
Ruchi Jain ◽  
Ravi Manjithaya ◽  
S S Vasan ◽  
Paturu Kondaiah ◽  
...  
Keyword(s):  
Gene Expression ◽  
Male Infertility ◽  
Differential Gene Expression ◽  
Germ Cells ◽  
Expression Patterns ◽  
Gene Expression Pattern ◽  
Obstructive Azoospermia ◽  
Sperm Retrieval ◽  
Testicular Germ Cell ◽  
Differential Gene

AbstractSpermatogenesis is characterized by sequential gene-expression at precise stages in progression of differentiation of the germ cells. Any alteration in expression of the critical genes is responsible for arrest of spermatogenesis associated with infertility. Inspite of advances the differential gene expression accompanying spermatogenesis, the corresponding regulatory mechanisms and their correlation to human infertility have not been clearly established. This study aims to identify the gene expression pattern of the human testicular germ cells from the patients either with obstructive azoospermia with complete intra-testicular spermatogenesis or non-obstructive azoospermia with spermatogenesis arrested at different stages and correlate the same to infertility. The testicular transcriptomes of 3 OA and 8 NOA patients and pooled testicular RNA (commercial source) were analyzed for their differential gene expression to identify potential regulators of spermatogenesis and the results were further validated in all of the 44 patients clinically diagnosed with azoospermia undergoing sperm retrieval surgery over the study period and 4 control samples included in this study. Analyses of the differential transcriptome led to identification of genes enriched in a specific testicular cell type and subsequently, several regulators of the diploid-double-diploid-haploid transitions in the human spermatogenesis were identified. Perturbations in the expression of these genes were identified as the potential causes of the spermatogenic arrest seen in azoospermia and thus the potential mediators of human male infertility. Another interesting observation was the increased autophagy in the testes of patients with non-obstructive azoospermia. The present study suggests that the regulation of the diploid-double-diploid-haploid transition is multigenic with the tandem alteration of several genes resulting in infertility. In conclusion, this study identified some of the genetic regulators controlling spermatogenesis using comparative transcriptome analyses of testicular tissues from azoospremic individuals and showed how alterations in several genes results in disruption of spermatogenesis and subsequent infertility. This study also provides interesting insights into the gene expression patterns of the Indian population that were not available earlier.

scholarly journals Role of antimicrobial peptide DEFB126 mutation in pathogenesis of male idiopathic infertility

2021 ◽  
Vol 23 (5) ◽  
pp. 1115-1124
Author(s):  
E. M. Khasanova ◽  
L. V. Gankovskaya ◽  
V. V. Burmakina
Keyword(s):  
Gene Expression ◽  
Male Infertility ◽  
Sperm Motility ◽  
Mutant Allele ◽  
Reproductive Tract ◽  
Control Group ◽  
Idiopathic Infertility ◽  
Fold Reduction ◽  
Distribution Frequency

Male infertility is a multifactorial disease, and elucidation of etiopathogenetic mechanisms of its progression is a topical issue. High percentage of the “idiopathic infertility” diagnosis is largely cased by inability to establish etiology of decrease in reproductive spermatic function. Mutation of в-defensin DEFB126 gene is supposed to affect the fertilizing ability of spermatozoa at different levels: it may decrease their ability to migrate through the cervical mucus and reduce binding capacity to epithelial layer of upper female reproductive tract, and it may also increase susceptibility for infections of reproductive tract, due to impairment of local protective function of defensins. Thus, the aim of the present study was to examine possible role of rs11468374 gene polymorphism of the DEFB126 gene in pathogenesis of male idiopathic infertility. Patients and methods: The group of patient with decreased fertility included 54 male subjects, ages 34 to 42, with a control group of 19 ejaculate donors without acute or chronic disease aged 28 to 36. The indicators of sperm motility in the Moscow population were compared with individual levels of DEFB126 gene expression, as well as with estimated distribution frequency of rs11468374 alleles and genotypes among the subjects.As compared with the control group, the infertile patients exhibited a more than seven-fold reduction of DEFB126 gene expression. Analysis of distribution frequency for alleles and genotypes rs11468374 polymorphic marker of the DEFB126 gene revealed that the mutant allele is detected almost twice as often in males with infertility, as compared with control group. No cases with the DEFB126 del/del genotype were found among the control group, in contrary to 16.1% in the group of patients. The patients with DEFB126 del/del genotype exhibited 5.2-fold reduction of sperm motility. Thus, the data obtained may be used to extend our knowledge on the pathogenetic mechanisms of male idiopathic infertility and to improve techniques for its diagnostics, as well as to provide personalized approach to the treatment of male reproductive disorders. The association between carriage of del mutant allele and decreased level of sperm motility suggests a role of this polymorphism in pathogenesis of male infertility. A general decrease in the level of DEFB126 gene expression in the patients affected by infertility also presumes a contribution of defensin 126 to pathogenesis of the disorder.

scholarly journals YTHDF2 is essential for spermatogenesis and fertility through mediating a wave of transcript transition during spermatogonial differentiation

2020 ◽  
Author(s):  
Xin-Xi Zhao ◽  
Zhen Lin ◽  
Yong Fan ◽  
Yu-Jie Zhang ◽  
Fei Li ◽  
...  
Keyword(s):  
Gene Expression ◽  
Male Infertility ◽  
Germ Cell ◽  
Embryonic Stem ◽  
Stem Cell Differentiation ◽  
Embryonic Stem Cell Differentiation ◽  
Transcriptional Level ◽  
Potential Candidate ◽  
Rna Seq ◽  
Mutation Strategy

AbstractThe dynamic and reversible regulation roles of m6A modification, and the characterization of m6A readers have provided new insights into spermatogenesis at post-transcriptional level. YTHDF2 has been reported to recognize and mediate the m6A-containing transcripts decay during the mouse oocyte mature, embryonic stem cell differentiation, neural development, and zebrafish maternal-to-zygotic transition. However, the roles of YTHDF2 in mammalian spermatogenesis are uncertain. Here, we generated germ cell-specific Ythdf2 mutants (Ythdf2-vKO) at a C57BL/6J background, and demonstrated that YTHDF2 was essential for mouse spermatogenesis and fertility. Ythdf2-vKO provided oligoasthenoteratozoospermia (OAT) phenotype with increased apoptosis in germ cells. High-throughput RNA-seq of the testis tissue showed the failure of the degradation of a wave of YTHDF2 target mRNA. Interestingly, RNA-seq analysis combined with our previous single-cell transcriptomics data of mouse spermatogenesis pointed out the failure of a wave of transcript transition during the spermatogenesis of Ythdf2-vKO, which was confirmed by gene expression analysis of diplotene spermatocytes and round spermatids obtained through fluorescence-activated cell sorting using qPCR. Our study demonstrates the fundamental role of YTHDF2 during mouse spermatogenesis and provides a potential candidate for the diagnosis of male infertility with OAT syndrome.Author summaryMale infertility is becoming a worldwide health problem. Male gamete is generated through spermatogenesis, which is a complicated developmental process with dynamic transcriptome changes. RNA m6A modification has been reported as the most prominently internal mRNA modification, which control the tune of gene expression through mRNA splicing, export, translation and decay. RNA m6A modification is catalyzed by “writers”, and could be removed by “erasers”. The m6A modification enzymes are reported to play important roles during spermatogenesis. Given that the biological function of m6A modification are mediated through its “readers”, its readers might be proposed to be involved in the regulation of spermatogenesis. YTHDF2, as a reader of m6A modification, has been reported to mediate the m6A-containing transcripts decay. To explore the roles of YTHDF2 in spermatogenesis, we used germ cell-specific mutation strategy to knock out the mouse Ythdf2. The mutants provided oligoasthenoteratozoospermia phenotype. Our study demonstrate that YTHDF2 is essential for mouse spermatogenesis. YTHDF2 could be a potential candidate for the diagnosis of oligoasthenoteratozoospermia syndrome.

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