scholarly journals SYCP2 translocation-mediated dysregulation and frameshift variants cause human male infertility

2019 ◽  
Author(s):  
Samantha L.P. Schilit ◽  
Shreya Menon ◽  
Corinna Friedrich ◽  
Tammy Kammin ◽  
Ellen Wilch ◽  
...  
Keyword(s):  
Male Infertility ◽  
Exome Sequencing ◽  
Synaptonemal Complex ◽  
Budding Yeast ◽  
Reproductive Age ◽  
Severe Oligozoospermia ◽  
Common Cause ◽  
Human Male ◽  
Defective Spermatogenesis

ABSTRACTInfertility is one of the most common disorders for men of reproductive age. To identify novel genetic etiologies, we studied a male with severe oligozoospermia and 46, XY,t(20;22)(q13.3;q11.2). We identified exclusive overexpression of SYCP2 from the der(20) allele that is hypothesized to result from enhancer adoption. Modeling the dysregulation in budding yeast resulted in disruption of the synaptonemal complex, a common cause of defective spermatogenesis in mammals. Exome sequencing of infertile males revealed three novel heterozygous SYCP2 frameshift variants in additional subjects with cryptozoospermia and azoospermia. This study provides the first evidence of SYCP2-mediated male infertility in humans.

scholarly journals Usp26 mutation in mice leads to defective spermatogenesis depending on genetic background

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Kohei Sakai ◽  
Chizuru Ito ◽  
Mizuki Wakabayashi ◽  
Satoko Kanzaki ◽  
Toshiaki Ito ◽  
...  
Keyword(s):  
Male Infertility ◽  
Genetic Background ◽  
Chiasma Formation ◽  
Mutant Mice ◽  
Reproductive Capacity ◽  
Wild Type ◽  
Human Male ◽  
Subsequent Decrease ◽  
Head Morphology ◽  
Defective Spermatogenesis

Abstract Spermatogenesis is a reproductive system process that produces sperm. Ubiquitin specific peptidase 26 (USP26) is an X chromosome-linked deubiquitinase that is specifically expressed in the testes. It has long been controversial whether USP26 variants are associated with human male infertility. Thus, in the present study, we introduced a mutation into the Usp26 gene in mice and found that Usp26 mutant males backcrossed to a DBA/2 background, but not a C57BL/6 background, were sterile or subfertile and had atrophic testes. These findings indicate that the effects of the Usp26 mutation on male reproductive capacity were influenced by genetic background. Sperm in the cauda epididymis of Usp26 mutant mice backcrossed to a DBA/2 background were decreased in number and showed a malformed head morphology compared to those of wild-type mice. Additionally, histological examinations of the testes revealed that the number of round and elongated spermatids were dramatically reduced in Usp26 mutant mice. The mutant mice exhibited unsynapsed chromosomes in pachynema and defective chiasma formation in diplonema, which presumably resulted in apoptosis of metaphase spermatocytes and subsequent decrease of spermatids. Taken together, these results indicate that the deficiencies in fertility and spermatogenesis caused by mutation of Usp26 were dependent on genetic background.

scholarly journals Tachykinins and Kisspeptins in the Regulation of Human Male Fertility

2019 ◽  
Vol 9 (1) ◽  
pp. 113 ◽  
Author(s):  
Víctor Blasco ◽  
Francisco M. Pinto ◽  
Cristina González-Ravina ◽  
Esther Santamaría-López ◽  
Luz Candenas ◽  
...  
Keyword(s):  
Male Infertility ◽  
Male Fertility ◽  
Animal Species ◽  
Reproductive Age ◽  
Diagnosis And Treatment ◽  
Male Factor ◽  
Human Male ◽  
Human Fertility ◽  
The World

Infertility is a global disease affecting one out of six couples of reproductive age in the world, with a male factor involved in half the cases. There is still much to know about the regulation of human male fertility and thus we decided to focus on two peptide families that seem to play a key role in this function: tachykinins and kisspeptins. With this aim, we conducted an exhaustive review in order to describe the role of tachykinins and kisspeptins in human fertility and their possible implications in infertility etiopathogenesis. Many advances have been made to elucidate the roles of these two families in infertility, and multiple animal species have been studied, including humans. All of this knowledge could lead to new advances in male infertility diagnosis and treatment, but further research is needed to clarify all the implications of tachykinins and kisspeptins in fertility.

scholarly journals Variations in Antioxidant Genes and Male Infertility

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Bolan Yu ◽  
Zhaofeng Huang
Keyword(s):  
Male Infertility ◽  
Population Studies ◽  
Sperm Quality ◽  
Synergistic Effects ◽  
Related Factor ◽  
Antioxidant Genes ◽  
Functional Polymorphisms ◽  
Normal Sperm ◽  
Oxide Synthase ◽  
Defective Spermatogenesis

Oxidative stress and reactive oxygen species (ROS) are generated from both endogenous and environmental resources, which in turn may cause defective spermatogenesis and male infertility. Antioxidant genes, which include catalase (CAT), glutathione peroxidase (GPX), glutathioneS-transferase (GST), nitric oxide synthase (NOS), nuclear factor erythroid 2-related factor 2 (NRF2), and superoxide dismutase (SOD), play important roles in spermatogenesis and normal sperm function. In this review, we discuss the association between variations in major antioxidant genes and male infertility. Numerous studies have suggested that genetic disruption or functional polymorphisms in these antioxidant genes are associated with a higher risk for male infertility, which include low sperm quality, oligoasthenoteratozoospermia, oligozoospermia, and subfertility. The synergistic effects of environmental ROS and functional polymorphisms on antioxidant genes that result in male infertility have also been reported. Therefore, variants in antioxidant genes, which independently or synergistically occur with environmental ROS, affect spermatogenesis and contribute to the occurrence of male infertility. Large cohort and multiple center-based population studies to identify new antioxidant genetic variants that increase susceptibility to male infertility as well as validate its potential as genetic markers for diagnosis and risk assessment for male infertility for precise clinical approaches are warranted.

scholarly journals Genetic Basis of Male Infertility

2013 ◽  
Vol 4 (1) ◽  
pp. 37-39 ◽  
Author(s):  
Mosammat Rashida Begum ◽  
Mariya Ehsan
Keyword(s):  
Genetic Testing ◽  
Male Infertility ◽  
Medical Treatment ◽  
Intracytoplasmic Sperm Injection ◽  
Chromosomal Abnormality ◽  
Genetic Disease ◽  
Genetic Basis ◽  
Common Cause ◽  
Near Future ◽  
Spermatogenic Failure

Infertility is a couple's problem. Almost 50% case males are responsible for infertility. Most common cause is oligospermia and azoospermia and approximately 5% to 15% of men with azoospermia and severe oligospermia may have a chromosomal abnormality. Men with significant spermatogenic compromise are the candidates of intracytoplasmic sperm injection (ICSI). Raised FSH level above 9 is an indication of spermatogenic compromise. So, medical treatment for these patients is waste of time and money. Early attempt of assisted reproduction is ideal to avoid the crisis of total spermatogenic failure in near future. But before going for ICSI genetic testing if possible and proper counseling about possibilities of transmission of genetic disease to offspring is necessary. DOI: http://dx.doi.org/10.3329/akmmcj.v4i1.13683 AKMMC J 2013: 4(1): 37-39  

scholarly journals Review of Gynaecological Diagnoses and Surgeries Performed at a Tertiary Health Facility in Niger-Delta of Nigeria from 2012-2017: Implications for Healthcare Planning and Budgeting

2020 ◽  
pp. 1-10
Author(s):  
P. A. Awoyesuku ◽  
D. A. MacPepple ◽  
B. O. Altraide ◽  
D. H. John
Keyword(s):  
Health Facility ◽  
Uterine Fibroid ◽  
Assisted Reproductive Technologies ◽  
Descriptive Analysis ◽  
Reproductive Technologies ◽  
Reproductive Age ◽  
University Teaching ◽  
Common Cause ◽  
Healthcare Planning ◽  
Pelvic Malignancies

Background: Gynaecological disorders are a particularly common cause of morbidity and mortality among women of reproductive age and a common cause of hospital presentation/admission and surgery. Objective: This study sought to review gynaecological diagnoses and surgeries performed in a tertiary health facility from 2012 to 2017 and its implication for healthcare planning and budgeting. Methodology: This was a retrospective review of all gynaecological diagnoses and surgeries seen in the Rivers State University Teaching Hospital (RSUTH) from 2012 to 2017. Data were retrieved using a proforma comprising of year, gynaecological diagnosis and gynaecological surgeries. Data obtained was entered into Microsoft Excel for descriptive analysis. Results: The proportion of clinic attendees declined from an average of 23% in the first three years (2012-2014) to about 10% in the last three years (2015-2017). The most common gynaecological diagnosis were uterine fibroid (33.3%), infertility 28.1% (primary 5.7%, secondary 22.4%), PID (5.9%), ovarian tumour (4.2%), secondary amenorrhea (3.4%) and pelvic malignancies (3.4%). The commonest major surgeries were myomectomy 441(33.7%), salpingectomy 345(26.4%), hysterectomy 168(12.8%) and cervical cerclage 122(9.3%). The commonest minor surgeries were manual vacuum aspiration 314(41.0%), examination under anaesthesia and biopsy 110(14.3%) and adhesiolysis for synechiae 97(12.6%). The duo of uterine fibroid and infertility made up 50%-70% of all gynaecological diagnoses. Conclusion: This study showed that there has been a steady decline in gynaecological consultations over the years. However, the duo of uterine fibroid and infertility made up half to three-quarter of all gynaecological diagnoses over the 6 years. Infertility and uterine fibroids have a long cause and effect association. Healthcare policies and budgeting should be increased towards tackling these conditions, especially the setting up of a fertility center to provide assisted reproductive technologies and laparoscopy to improve practice and patient outcome.

Relationship Between Hyperviscosity and Sex Hormone in Azoospermia and Oligozoospermia Patients Compares with The Control Group

2019 ◽  
Vol 10 (04) ◽  
pp. 637-639
Author(s):  
Hayder L F AL-Msaid ◽  
H A Waleed ◽  
Alaauldeen S M AL-Sallami
Keyword(s):  
Data Analysis ◽  
Male Infertility ◽  
Sex Hormones ◽  
Seminal Fluid ◽  
Strong Relationship ◽  
Sex Hormone ◽  
Control Group ◽  
Common Cause ◽  
Sperm Counts ◽  
Sperm Dysfunction

Background: Seminal fluid is important factor for successful fertility, Sperm dysfunction is the most common cause of male infertility. Aim of study: To compare the sex hormone in patient with azoospermia, Oligozoospermia and Normospermia fertile men as a control To find out the causes of semen viscosity. Patients and methods: Data analysis from azoospermia patient (n = 35) and Oligozoospermia (n = 35) and Normospermia fertile men as a control (n = 13). Results: The results of this study revealed significant reduction (p andGLT;0.05) semen was reduced in azoospermia infertile patient (mean ± Std. Error 0.76 ± 0.21 also reduced in Oligozoospermia 0.71 ± 0.23 while showed no significant FSH and LH level between azoospermia and Oligozoospermia compare with Normospermia fertile men. Conclusion: The viscosity in semen has a strong relationship with low sperm counts is an important factor with sex hormones therefore it is the cause affecting the motile spermatozoa.

Germline Telomere Attrition is Associated with Human Male Infertility

2016 ◽  
Vol 5 (2) ◽  
pp. 37-44
Author(s):  
S. Pathak ◽  
◽  
A.S. Multani ◽  
S.H. Sohn ◽  
N.J. Gupta ◽  
...  
Keyword(s):  
Male Infertility ◽  
Telomere Attrition ◽  
Human Male

Polycystic ovary syndrome: reproductive aspects

2011 ◽  
pp. 1229-1234
Author(s):  
Sophie Catteau-Jonard ◽  
Cécile Gallo ◽  
Didier Didier
Keyword(s):  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Reproductive Age ◽  
Therapeutic Approaches ◽  
Women Of Reproductive Age ◽  
Ovary Syndrome ◽  
Common Cause ◽  
The Metabolic Syndrome

The polycystic ovary syndrome (PCOS) is the most common cause of anovulation and hyperandrogenism in women, affecting between 5 and 10% of women of reproductive age worldwide (1). Although this difficult topic in endocrine gynaecology is under extensive research, controversies still remain about the pathophysiology, diagnosis, and therapy of PCOS. The PCOS phenotype can be structured in three components: manifestations of anovulation, hyperandrogenism, and the metabolic syndrome (of which hyperinsulinaemia secondary to insulin resistance is the central abnormality). The latter two are addressed in other chapters. Our knowledge about the mechanism of disturbed folliculogenesis in PCOS that is responsible for its reproductive aspects has much increased these last years, thus opening new avenues for the diagnostic and therapeutic approaches.

scholarly journals Haploid male germ cells—the Grand Central Station of protein transport

2020 ◽  
Vol 26 (4) ◽  
pp. 474-500 ◽  
Author(s):  
Christiane Pleuger ◽  
Mari S Lehti ◽  
Jessica EM Dunleavy ◽  
Daniela Fietz ◽  
Moira K O’Bryan
Keyword(s):  
Male Infertility ◽  
Protein Transport ◽  
Model System ◽  
Sperm Head ◽  
Vesicle Transport ◽  
Future Research ◽  
Significant Percentage ◽  
Human Male ◽  
Abnormal Sperm ◽  
Haploid Male

Abstract BACKGROUND The precise movement of proteins and vesicles is an essential ability for all eukaryotic cells. Nowhere is this more evident than during the remarkable transformation that occurs in spermiogenesis—the transformation of haploid round spermatids into sperm. These transformations are critically dependent upon both the microtubule and the actin cytoskeleton, and defects in these processes are thought to underpin a significant percentage of human male infertility. OBJECTIVE AND RATIONALE This review is aimed at summarising and synthesising the current state of knowledge around protein/vesicle transport during haploid male germ cell development and identifying knowledge gaps and challenges for future research. To achieve this, we summarise the key discoveries related to protein transport using the mouse as a model system. Where relevant, we anchored these insights to knowledge in the field of human spermiogenesis and the causality of human male infertility. SEARCH METHODS Relevant studies published in English were identified using PubMed using a range of search terms related to the core focus of the review—protein/vesicle transport, intra-flagellar transport, intra-manchette transport, Golgi, acrosome, manchette, axoneme, outer dense fibres and fibrous sheath. Searches were not restricted to a particular time frame or species although the emphasis within the review is on mammalian spermiogenesis. OUTCOMES Spermiogenesis is the final phase of sperm development. It results in the transformation of a round cell into a highly polarised sperm with the capacity for fertility. It is critically dependent on the cytoskeleton and its ability to transport protein complexes and vesicles over long distances and often between distinct cytoplasmic compartments. The development of the acrosome covering the sperm head, the sperm tail within the ciliary lobe, the manchette and its role in sperm head shaping and protein transport into the tail, and the assembly of mitochondria into the mid-piece of sperm, may all be viewed as a series of overlapping and interconnected train tracks. Defects in this redistribution network lead to male infertility characterised by abnormal sperm morphology (teratozoospermia) and/or abnormal sperm motility (asthenozoospermia) and are likely to be causal of, or contribute to, a significant percentage of human male infertility. WIDER IMPLICATIONS A greater understanding of the mechanisms of protein transport in spermiogenesis offers the potential to precisely diagnose cases of male infertility and to forecast implications for children conceived using gametes containing these mutations. The manipulation of these processes will offer opportunities for male-based contraceptive development. Further, as increasingly evidenced in the literature, we believe that the continuous and spatiotemporally restrained nature of spermiogenesis provides an outstanding model system to identify, and de-code, cytoskeletal elements and transport mechanisms of relevance to multiple tissues.

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