scholarly journals Epigenetic Inactivation of SOX30 Is Associated with Male Infertility and Offers a Therapy Target for Non-obstructive Azoospermia

2020 ◽  
Vol 19 ◽  
pp. 72-83 ◽  
Author(s):  
Fei Han ◽  
Xiao Jiang ◽  
Zhi-ming Li ◽  
Xuan Zhuang ◽  
Xi Zhang ◽  
...  
Keyword(s):  
Male Infertility ◽  
Obstructive Azoospermia ◽  
Epigenetic Inactivation ◽  
Therapy Target

scholarly journals Cellular Therapy via Spermatogonial Stem Cells for Treating Impaired Spermatogenesis, Non-Obstructive Azoospermia

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1779
Author(s):  
Nesma E. Abdelaal ◽  
Bereket Molla Tanga ◽  
Mai Abdelgawad ◽  
Sahar Allam ◽  
Mostafa Fathi ◽  
...  
Keyword(s):  
Stem Cells ◽  
Male Infertility ◽  
Cellular Therapy ◽  
Antihypertensive Drugs ◽  
Testicular Biopsy ◽  
Testicular Tissue ◽  
Spermatogonial Stem Cells ◽  
Obstructive Azoospermia ◽  
Promising Alternative ◽  
Major Health Problem

Male infertility is a major health problem affecting about 8–12% of couples worldwide. Spermatogenesis starts in the early fetus and completes after puberty, passing through different stages. Male infertility can result from primary or congenital, acquired, or idiopathic causes. The absence of sperm in semen, or azoospermia, results from non-obstructive causes (pretesticular and testicular), and post-testicular obstructive causes. Several medications such as antihypertensive drugs, antidepressants, chemotherapy, and radiotherapy could lead to impaired spermatogenesis and lead to a non-obstructive azoospermia. Spermatogonial stem cells (SSCs) are the basis for spermatogenesis and fertility in men. SSCs are characterized by their capacity to maintain the self-renewal process and differentiation into spermatozoa throughout the male reproductive life and transmit genetic information to the next generation. SSCs originate from gonocytes in the postnatal testis, which originate from long-lived primordial germ cells during embryonic development. The treatment of infertility in males has a poor prognosis. However, SSCs are viewed as a promising alternative for the regeneration of the impaired or damaged spermatogenesis. SSC transplantation is a promising technique for male infertility treatment and restoration of spermatogenesis in the case of degenerative diseases such as cancer, radiotherapy, and chemotherapy. The process involves isolation of SSCs and cryopreservation from a testicular biopsy before starting cancer treatment, followed by intra-testicular stem cell transplantation. In general, treatment for male infertility, even with SSC transplantation, still has several obstacles. The efficiency of cryopreservation, exclusion of malignant cells contamination in cancer patients, and socio-cultural attitudes remain major challenges to the wider application of SSCs as alternatives. Furthermore, there are limitations in experience and knowledge regarding cryopreservation of SSCs. However, the level of infrastructure or availability of regulatory approval to process and preserve testicular tissue makes them tangible and accurate therapy options for male infertility caused by non-obstructive azoospermia, though in their infancy, at least to date.

Decreased expression of DNA methyltransferases in the testes of patients with non-obstructive azoospermia leads to changes in global DNA methylation levels

2019 ◽  
Vol 31 (8) ◽  
pp. 1386 ◽  
Author(s):  
Fatma Uysal ◽  
Gokhan Akkoyunlu ◽  
Saffet Ozturk
Keyword(s):  
Dna Methylation ◽  
Male Infertility ◽  
De Novo ◽  
Biological Effects ◽  
Testicular Biopsy ◽  
Round Spermatid ◽  
Dna Methyltransferases ◽  
Global Dna Methylation ◽  
Obstructive Azoospermia ◽  
Spermatogenic Cells

DNA methylation plays key roles in epigenetic regulation during mammalian spermatogenesis. DNA methyltransferases (DNMTs) function in de novo and maintenance methylation processes by adding a methyl group to the fifth carbon atom of the cytosine residues within cytosine–phosphate–guanine (CpG) and non-CpG dinucleotide sites. Azoospermia is one of the main causes of male infertility, and is classified as obstructive (OA) or non-obstructive (NOA) azoospermia based on histopathological characteristics. The molecular background of NOA is still largely unknown. DNA methylation performed by DNMTs is implicated in the transcriptional regulation of spermatogenesis-related genes. The aim of the present study was to evaluate the cellular localisation and expression levels of the DNMT1, DNMT3A and DNMT3B proteins, as well as global DNA methylation profiles in testicular biopsy samples obtained from men with various types of NOA, including hypospermatogenesis (hyposperm), round spermatid (RS) arrest, spermatocyte (SC) arrest and Sertoli cell-only (SCO) syndrome. In the testicular biopsy samples, DNMT1 expression and global DNA methylation levels decreased gradually from the hyposperm to SCO groups (P<0.05). DNMT3A expression was significantly decreased in the RS arrest, SC arrest and SCO groups compared with the hyposperm group (P<0.05). DNMT3B expression was significantly lower in the RS arrest and SCO groups than in the hyposperm group (P<0.05). Although both DNMT1 and DNMT3A were localised in the cytoplasm and nucleus of the spermatogenic cells, staining for DNMT3B was more intensive in the nucleus of spermatogenic cells. In conclusion, the findings suggest that significant changes in DNMT expression and global DNA methylation levels in spermatogenic cells may contribute to development of male infertility in the NOA groups. Further studies are needed to determine the molecular biological effects of the altered DNMT expression and DNA methylation levels on development of male infertility.

scholarly journals Multicenter study of genetic abnormalities associated with severe oligospermia and non-obstructive azoospermia

2017 ◽  
Vol 46 (1) ◽  
pp. 107-114 ◽  
Author(s):  
Chong Xie ◽  
Xiangfeng Chen ◽  
Yulin Liu ◽  
Zhengmu Wu ◽  
Ping Ping
Keyword(s):  
Genetic Testing ◽  
Male Infertility ◽  
Multicenter Study ◽  
Chromosomal Abnormalities ◽  
Eastern China ◽  
Genetic Defects ◽  
Obstructive Azoospermia ◽  
Assisted Reproductive Technique ◽  
Severe Oligozoospermia ◽  
Genetic Abnormalities

Objective * Chong Xie, Xiangfeng Chen, and Yulin Liu contributed equally to this work. Genetic defects are identified in nearly 20% of infertile males. Determining the frequency and types of major genetic abnormalities in severe male infertility helps inform appropriate genetic counseling before assisted reproductive techniques. Methods Cytogenetic results of 912 patients with non-obstructive azoospermia (NOA) and severe oligozoospermia (SOS) in Eastern China were reviewed in this multicenter study from January 2011 to December 2015. Controls were 215 normozoospermic men with offspring. Results Among all patients, 22.6% (206/912) had genetic abnormalities, including 27.3% (146/534) of NOA patients and 15.9% (60/378) of SOS patients. Chromosomal abnormalities (all autosomal) were detected in only 1.9% (4 /215) of controls. In NOA patients, sex chromosomal abnormalities were identified in 25.8% (138/534), of which 8% (43/534) had a 47,XXY karyotype or its mosaic; higher than the SOS group prevalence (1.1%; 4/378). The incidence of Y chromosome microdeletions was lower in the SOS group (13.2%; 50/378) than in the NOA group (17.8%; 95/534). Conclusions The high prevalence of genetic abnormalities in our study indicates the importance of routine genetic testing in severe male infertility diagnosis. This may help determine the choice of assisted reproductive technique and allow specific pre-implantation genetic testing to minimize the risk of transmitting genetic defects.

A modern view of male infertility

1994 ◽  
Vol 6 (1) ◽  
pp. 93 ◽  
Author(s):  
SJ Silber
Keyword(s):  
Male Infertility ◽  
Y Chromosome ◽  
Obstructive Azoospermia ◽  
Male Factor Infertility ◽  
Male Factor ◽  
Sperm Retrieval ◽  
Modern Approach ◽  
Vitro Fertilization ◽  
Defective Spermatogenesis

It is archaic to view male factor infertility today separately from in vitro fertilization (IVF) and treatment of the female partner. Oligoasthenozoospermia may be an inherited condition (most likely on the Y chromosome), and is refractory to any treatment of the male including hormones and varicocelectomy. IVF technology is the only justifiable approach for achieving a pregnancy in these couples. The reasons for this view and the suggested modern approach to couples with oligoasthenozoospermia are outlined in this review. However, obstructive azoospermia is different as it can be successfully corrected with microsurgery in over 90% of men. When it cannot be corrected, as in congenital absence of vas, microsurgical sperm retrieval combined with IVF can still be highly effective in producing pregnancy with sperm from the husband. The most important arena for research into male infertility in the next decade will be to map out the deletions on the Y chromosome that might result in defective spermatogenesis, and which probably cause most cases of non-obstructive male factor infertility.

The CFTR gene: male infertility and assisted conception

1999 ◽  
Vol 7 (2) ◽  
pp. 155-160 ◽  
Author(s):  
S Kulshrestha ◽  
A Makrigiannakis ◽  
P Patrizio
Keyword(s):  
Male Infertility ◽  
Vas Deferens ◽  
Cftr Gene ◽  
Obstructive Azoospermia ◽  
Male Factor Infertility ◽  
Assisted Conception ◽  
Male Factor ◽  
Fertility Treatments ◽  
Bilateral Absence ◽  
Testicular Failure

Approximately 30–40% of couples seeking fertility treatments have male factor infertility. Their dysfunctions include azoospermia, oligozoospermia, asthenozoospermia and teratozoospermia. Those with azoospermia represent about 25% of the total, and of these about 30% have an obstructive process while the remaining have either primary or secondary testicular failure. In the obstructive azoospermia group, 25% of males have congenital bilateral absence of the vas deferens (CBAVD).

scholarly journals TRIM71 Deficiency Causes Germ Cell Loss During Mouse Embryogenesis and Is Associated With Human Male Infertility

2021 ◽  
Vol 9 ◽  
Author(s):  
Lucia A. Torres-Fernández ◽  
Jana Emich ◽  
Yasmine Port ◽  
Sibylle Mitschka ◽  
Marius Wöste ◽  
...  
Keyword(s):  
Male Infertility ◽  
Germ Cell ◽  
Cell Line ◽  
Rna Binding ◽  
Seminiferous Tubules ◽  
Obstructive Azoospermia ◽  
Sequencing Analysis ◽  
Mouse Embryogenesis ◽  
Human Male

Mutations affecting the germline can result in infertility or the generation of germ cell tumors (GCT), highlighting the need to identify and characterize the genes controlling germ cell development. The RNA-binding protein and E3 ubiquitin ligase TRIM71 is essential for embryogenesis, and its expression has been reported in GCT and adult mouse testes. To investigate the role of TRIM71 in mammalian germ cell embryonic development, we generated a germline-specific conditional Trim71 knockout mouse (cKO) using the early primordial germ cell (PGC) marker Nanos3 as a Cre-recombinase driver. cKO mice are infertile, with male mice displaying a Sertoli cell-only (SCO) phenotype which in humans is defined as a specific subtype of non-obstructive azoospermia characterized by the absence of germ cells in the seminiferous tubules. Infertility in male Trim71 cKO mice originates during embryogenesis, as the SCO phenotype was already apparent in neonatal mice. The in vitro differentiation of mouse embryonic stem cells (ESCs) into PGC-like cells (PGCLCs) revealed reduced numbers of PGCLCs in Trim71-deficient cells. Furthermore, TCam-2 cells, a human GCT-derived seminoma cell line which was used as an in vitro model for PGCs, showed proliferation defects upon TRIM71 knockdown. Additionally, in vitro growth competition assays, as well as proliferation assays with wild type and CRISPR/Cas9-generated TRIM71 mutant NCCIT cells showed that TRIM71 also promotes proliferation in this malignant GCT-derived non-seminoma cell line. Importantly, the PGC-specific markers BLIMP1 and NANOS3 were consistently downregulated in Trim71 KO PGCLCs, TRIM71 knockdown TCam-2 cells and TRIM71 mutant NCCIT cells. These data collectively support a role for TRIM71 in PGC development. Last, via exome sequencing analysis, we identified several TRIM71 variants in a cohort of infertile men, including a loss-of-function variant in a patient with an SCO phenotype. Altogether, our work reveals for the first time an association of TRIM71 deficiency with human male infertility, and uncovers further developmental roles for TRIM71 in the germline during mouse embryogenesis.

scholarly journals Hsa-miR-27a-3p overexpression in men with nonobstructive azoospermia: A case-control study

2020 ◽  
Author(s):  
Hamid Norioun ◽  
Majid Motovali-bashi ◽  
Seyed Morteza Javadirad
Keyword(s):  
Male Infertility ◽  
Case Control Study ◽  
Quantitative Polymerase Chain Reaction ◽  
Case Control ◽  
Micro Rna ◽  
Expression Level ◽  
Obstructive Azoospermia ◽  
Aberrant Expression ◽  
Micro Rnas ◽  
Control Study

Background: The role of KDM3A and its downstream genes in male fertility has been approved in animal models. Additionally, the expression shrinkage of KDM3A is significantly correlated with human azoospermia phenotype. Aberrant expression of micro-RNAs could mislead spermatogenesis and mostly lead to diverse phenotypes of male infertility. Objective: The aim of this study was to evaluate the expression level of hsa-miR-27a- 3p in azoospermic men to reveal its possible association with infertility. Materials and Methods: This case-control study was conducted on 30 azoospermic men, of whom, 19 had non obstructive azoospermia (NOA) and 11 obstructive azoospermia (OA) according to the pathological examinations. Comprehensive bioinformatics investigations were performed securely and hsa-miR-27a-3p was selected afterward. Reverse Transcriptase-quantitative polymerase chain reaction (RTqPCR) method was used and statistical analysis was performed to compare the expression level of hsa-miR-27a-3p in both OA and NOA individuals. Results: In silico analysis suggested hsa-miR-27a-3p, with its potential binding ability to target KDM3A transcripts. The expression analysis of candidate hsa-miR-27a-3p indicated its significant overexpression in NOA men. Conclusion: The hsa-miR-27a-3p was overexpressed in NOA men compared to OA-control individuals. As a consequence, the overexpressed micro-RNA could downregulate directly KDM3A and indirectly TNP1 and PRM1. Therefore, spermatogenesis could be misled and male infertility could be developed. Key words: hsa-miR-27a-3p, Male infertility, KDM3A.

scholarly journals The value of ultrasound in diagnosis of male infertility

2004 ◽  
Vol 57 (11-12) ◽  
pp. 551-555
Author(s):  
Sanja Stojanovic ◽  
Mira Govorcin ◽  
Dusan Hadnadjev ◽  
Goran Marusic ◽  
Slavica Senicar ◽  
...  
Keyword(s):  
Male Infertility ◽  
Vas Deferens ◽  
Ultrasound Examination ◽  
Color Doppler ◽  
Transrectal Ultrasound ◽  
Testicular Atrophy ◽  
Obstructive Azoospermia ◽  
Pathological Conditions ◽  
Common Causes ◽  
Male Patients

Introduction The number of male patients with clinical presentation of infertility, especially secondary infertility after infections, is increasing every day. Contemporary urological standards in defining male infertility include ultrasound examination. Ultrasound examination of the scrotum using color doppler is of great importance. Diagnosis of male infertility Testicular atrophy, microlithiasis and varicocele are the most common causes of male infertility. Microlithiasis and classical testicular microlithiasis are not directly associated with infertility. Gray scale sonography is used in evaluation of the dilatation of the testicular veins, but color Doppler made a real contribution in revealing subclinical varicocele. Transrectal ultrasound is used in a number of pathological conditions of prostate, seminal vesicles and ducts. In cases of obstructive azoospermia it is important to find out the cause, such as focal prostatitis, cysts, ejaculatory ducts obstruction or absence of vas deferens. Conclusion UIltrasound is a noninvasive method easy to perform, which provides information without postexamination consequences such as strictures or obstructions, which are possible after invasive deferentography. Ultrasound guided biopsy, provides a new minimally invasive diagnostic tool in current urology.

Surgical treatment of male infertility

2017 ◽  
Author(s):  
Gert R Dohle
Keyword(s):  
Surgical Treatment ◽  
Male Infertility ◽  
Birth Defect ◽  
Low Cost ◽  
Unexplained Infertility ◽  
Testis Cancer ◽  
Obstructive Azoospermia ◽  
Infertile Men ◽  
Testis Volume ◽  
Fair Chance

Surgical treatment of male infertility is indicated in men with obstructive azoospermia due to epididymal and vassal blockage, in infertile men with a varicocele and oligozoospermia, and to harvest spermatozoa for future intracytoplasmic sperm injection (ICSI). Testis biopsy may be performed in men with normal testis volume and normal gonadotrophins to confirm the diagnosis of obstructive azoospermia. Furthermore, testis biopsies are indicated in men with risk factors for testis cancer, such as infertility and ultrasonograhic abnormalities.Varicocele repair seems effective in case of an infertility duration of at least 2 years, oligozoospermia, and otherwise unexplained infertility in a couple. The advantages of surgery in these couples are a fair chance of spontaneous pregnancies at relative low cost and with less obstetric problems and birth defect compared to pregnancies from IVF procedures.

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