scholarly journals Y chromosome is moving out of sex determination shadow

2022 ◽  
Vol 12 (1) ◽  
Author(s):  
Raheleh Heydari ◽  
Zohreh Jangravi ◽  
Samaneh Maleknia ◽  
Mehrshad Seresht-Ahmadi ◽  
Zahra Bahari ◽  
...  
Keyword(s):  
Sex Differences ◽  
Y Chromosome ◽  
Sex Hormones ◽  
Molecular Mechanisms ◽  
Response To Therapy ◽  
Aberrant Expression ◽  
Disease Mechanisms ◽  
Considerable Impact ◽  
Male Specific ◽  
Human Proteome Project

AbstractAlthough sex hormones play a key role in sex differences in susceptibility, severity, outcomes, and response to therapy of different diseases, sex chromosomes are also increasingly recognized as an important factor. Studies demonstrated that the Y chromosome is not a ‘genetic wasteland’ and can be a useful genetic marker for interpreting various male-specific physiological and pathophysiological characteristics. Y chromosome harbors male‑specific genes, which either solely or in cooperation with their X-counterpart, and independent or in conjunction with sex hormones have a considerable impact on basic physiology and disease mechanisms in most or all tissues development. Furthermore, loss of Y chromosome and/or aberrant expression of Y chromosome genes cause sex differences in disease mechanisms. With the launch of the human proteome project (HPP), the association of Y chromosome proteins with pathological conditions has been increasingly explored. In this review, the involvement of Y chromosome genes in male-specific diseases such as prostate cancer and the cases that are more prevalent in men, such as cardiovascular disease, neurological disease, and cancers, has been highlighted. Understanding the molecular mechanisms underlying Y chromosome-related diseases can have a significant impact on the prevention, diagnosis, and treatment of diseases.

scholarly journals The Snakeskin Gourami (Trichopodus pectoralis) Tends to Exhibit XX/XY Sex Determination

Fishes ◽  
2021 ◽  
Vol 6 (4) ◽  
pp. 43
Author(s):  
Thitipong Panthum ◽  
Nararat Laopichienpong ◽  
Ekaphan Kraichak ◽  
Worapong Singchat ◽  
Dung Ho My Nguyen ◽  
...  
Keyword(s):  
Sex Differences ◽  
Sex Determination ◽  
Y Chromosome ◽  
Cytogenetic Analysis ◽  
Genotyping By Sequencing ◽  
Sexually Dimorphic ◽  
Determination System ◽  
Sex Determination System ◽  
Male Specific ◽  
Determination Mechanism

The snakeskin gourami (Trichopodus pectoralis) has a high meat yield and is one of the top five aquaculture freshwater fishes in Thailand. The species is not externally sexually dimorphic, and its sex determination system is unknown. Understanding the sex determination system of this species will contribute to its full-scale commercialization. In this study, a cytogenetic analysis did not reveal any between-sex differences in chromosomal patterns. However, we used genotyping-by-sequencing to identify 4 male-linked loci and 1 female-linked locus, indicating that the snakeskin gourami tends to exhibit an XX/XY sex determination system. However, we did not find any male-specific loci after filtering the loci for a ratio of 100:0 ratio of males:females. This suggests that the putative Y chromosome is young and that the sex determination region is cryptic. This approach provides solid information that can help identify the sex determination mechanism and potential sex determination regions in the snakeskin gourami, allowing further investigation of genetic improvements in the species.

scholarly journals Long Non-coding Ribonucleic Acid as a Novel Diagnosis and Prognosis Biomarker of Bladder Cancer

2019 ◽  
Vol 7 (1) ◽  
pp. 28-34
Author(s):  
Saeid Afshar ◽  
Saman Seyedabadi ◽  
Massoud Saidijam ◽  
Pouria Samadi ◽  
Hamzeh Mazaherilaghab ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Molecular Mechanisms ◽  
Response To Therapy ◽  
Aberrant Expression ◽  
Ribonucleic Acids ◽  
Cellular Processes ◽  
Diagnosis And Prognosis ◽  
Pubmed Database ◽  
English Articles ◽  
Urologic Malignancies

Long non-coding ribonucleic acids (lncRNAs) are the largest group of non-coding RNAs and supposedly have a broad spectrum of diverse functions in normal cellular processes. This study was carried out to review the biological functions of candidate lncRNAs (i.e., H19, MALAT-1, TUG1, UCA-1, MEG-3, HOTAIR, CCAT2, AATBC, and the like) with aberrant expressions that play critical roles in bladder cancer (BC) initiation, progression, and metastasis. A formal narrative review was performed by searching the PubMed database for English articles using a combination of keywords such as "long non-coding RNA", "lncRNA", "cancer", "bladder cancer", "screening", "prognosis", "diagnosis", and "response to therapy". In addition, the existing literature was studied on biological function, aberrant expression, and the clinical applications of candidate lncRNAs in BC. By a better understanding of the molecular mechanisms of lncRNAs, they can be used as biomarkers for tumor signatures in urologic malignancies, which can improve screening, prognosis, diagnosis, and the treatment of BC.

scholarly journals The placenta and neurodevelopment: sex differences in prenatal vulnerability

2016 ◽  
Vol 18 (4) ◽  
pp. 459-464 ◽  
Keyword(s):  
Sex Differences ◽  
Molecular Mechanisms ◽  
Maternal Stress ◽  
Disease Risk ◽  
Risk And Resilience ◽  
Hyperactivity Disorder ◽  
Neurodevelopmental Disease ◽  
Genome Wide ◽  
A Genome ◽  
Male Specific

Prenatal insults, such as maternal stress, are associated with an increased neurodevelopmental disease risk and impact males significantly more than females, including increased rates of autism, mental retardation, stuttering, dyslexia, and attention deficit/hyperactivity disorder (ADHD). Sex differences in the placenta, which begin with sex chromosomes, are likely to produce sex-specific transplacental signals to the developing brain. Our studies and others have identified X-linked genes that are expressed at higher levels in the female placenta. Through a genome-wide screen after maternal stress in mice, we identified the X-linked gene O-linked N-acetylglucosamine transferase (OGT) and demonstrated its causality in neurodevelopmental programming producing a male-specific stress phenotype. Elucidating the sex-specific molecular mechanisms involved in transplacental signals that impact brain development is key to understanding the sex bias in neurodevelopmental disorders and is expected to yield novel insight into disease risk and resilience.

scholarly journals Molecular characterization of the Yp11.2 region deletion in the Chinese Han population

2021 ◽  
Author(s):  
Qianqian Pang ◽  
Qingai Lin ◽  
Di Wang ◽  
Zhenghao Sun ◽  
Junfang Wang
Keyword(s):  
Y Chromosome ◽  
Large Scale ◽  
Molecular Mechanisms ◽  
Tandem Repeats ◽  
Population Based ◽  
Chinese Han ◽  
Specific Sequence ◽  
Sequence Tagged Sites ◽  
Deletion Pattern ◽  
Male Specific

AbstractThe Y chromosome is male-specific and is important for spermatogenesis and male fertility. However, the Y chromosome is poorly characterized due to massive palindromes and inverted repeats, which increase the likelihood of genomic rearrangements, resulting in short tandem repeats on the Y chromosome or long fragment deletions. The present study reports a large-scale (2.573~2.648 Mb) deletion in the Yp11.2 region in a Chinese population based on the analysis of 34 selected Y-specific sequence-tagged sites and subsequent sequencing of the breakpoint junctions on the Y chromosome from 5,068,482–5,142,391 bp to 7,715,462–7,716,695 bp. The results of sequence analysis indicated that the deleted region included part or all of the following five genes: PCDH11Y, TSPY, AMELY, TBL1Y, and RKY. These genes are associated with spermatogenesis or amelogenesis and various other processes; however, specific physiological functions and molecular mechanisms of these genes remain unclear. Notably, individuals with this deletion pattern did not have an obvious pathological phenotype but manifested some degree of amelogenesis imperfecta.

scholarly journals OP0013 SEX DIFFERENCES IN AUTOIMMUNE DISEASE SUSCEPTIBILITY; A MULTI-OMIC APPROACH

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 8.1-8
Author(s):  
G. Robinson ◽  
K. Waddington ◽  
J. Peng ◽  
A. Radziszewska ◽  
H. Peckham ◽  
...  
Keyword(s):  
Sex Differences ◽  
Lipid Metabolism ◽  
Sex Hormones ◽  
Cell Function ◽  
Immune Cell ◽  
Density Lipoprotein ◽  
Hormone Treatment ◽  
Immune Cell Function ◽  
Immune Cell Subsets ◽  
Males And Females

Background:Males and females have altered immune responses resulting in variation in autoimmune and cardiovascular disease risk (CVR). Recently, these differences have played a role in the inflammatory response to COVID-19. Sex differences exist in the frequency and activity of immune-cell subsets but mechanisms underlying sexual dimorphism remain unknown. Juvenile-onset systemic lupus erythematosus (JSLE) is an autoimmune disorder that commonly emerges during puberty, has a strong female prevalence (female:male ratio, 4.5:1) and results in an increased CVR. JSLE is characterised by chronic inflammation and dyslipidaemia, where cardiovascular disease is a leading cause of mortality for patients. Our previous work identified a link between immune cell function and lipid metabolism in adult-onset SLE. We hypothesised that sex hormones could influence both lipid metabolism and immune cell function and this could determine sex-specific susceptibility to JSLE and associated CVR.Objectives:We investigated the role of sex hormones in modifying systemic lipid metabolism and inflammation.Methods:Nuclear magnetic resonance spectroscopy based serum metabolomics measuring over 130 lipoproteins (14-subsets with lipid compositions), flow cytometry measuring immune-cells, and RNA-sequencing were used to assess the metabolic and immune profile in young, pre/post-pubertal males (n=10/17) and females (n=10/23) and in individuals with gender-dysphoria (GD) under cross-hormone treatment (trans-male/female, n=26/25). This analysis was also performed on a cohort of post-pubertal male (n=12) and female (n=23) JSLE patients. Data was analysed by logistic regression, balanced random forest machine learning (BRF-ML), differential gene expression (DEG) and pathway analysis.Results:Post-pubertal males had significantly reduced cardio-protective high-density lipoprotein (HDL) subsets (p<0.0001) and increased cardio-pathogenic very-low-density lipoprotein subsets (p<0.0001) compared to females. These differences were not observed pre-puberty and were reversed significantly by cross-hormone treatment in GD individuals, suggesting that sex hormones regulate lipid metabolism in-vivo.BRF-ML (28 immune-cell subsets) identified an increased frequency of anti-inflammatory regulatory T-cells (Tregs) in post-pubertal males compared to females (p=0.0097). These Tregs were also more suppressive in males compared to females. Differences in Treg frequency were seen pre-puberty and were not altered by sex hormone treatment in GD individuals. However, Treg DEGs and functional transcriptomic pathways altered between post-pubertal males and females, including those involved in inflammatory signalling, overlapped with those altered by hormones in GD, suggesting hormones may also drive Treg functional changes. In addition, HDL metabolites modified by hormones showed differential associations with Treg phenotypes between post-pubertal males and females.Strikingly, sex differences in lipoproteins and Tregs were lost in JSLE, suggesting hormone signalling could be dysregulated in the pathogenesis of autoimmunity and could increase CVR for patients.Conclusion:Sex hormones drive altered lipoprotein metabolism and functional transcriptomic pathways in Tregs. Males have a lipoprotein profile associated with increased CVR, but a more anti-inflammatory immune profile compared to females. Together, this could explain sex differences in inflammatory disease susceptibilities and inform future sex-specific therapeutic strategies for the management of both JSLE and CVR.Acknowledgements:Lupus UKRosetrees TrustVersus ArthritisNIHR UCLH Biomedical Research CentreDisclosure of Interests:None declared

scholarly journals Regulatory Role of Sex Hormones in Cardiovascular Calcification

2021 ◽  
Vol 22 (9) ◽  
pp. 4620
Author(s):  
Holly J. Woodward ◽  
Dongxing Zhu ◽  
Patrick W. F. Hadoke ◽  
Victoria E. MacRae
Keyword(s):  
Cardiovascular Disease ◽  
Sex Differences ◽  
Sexual Dimorphism ◽  
Aortic Stenosis ◽  
Sex Hormones ◽  
Sex Hormone ◽  
Increased Risk ◽  
Male Sex ◽  
Primary Male

Sex differences in cardiovascular disease (CVD), including aortic stenosis, atherosclerosis and cardiovascular calcification, are well documented. High levels of testosterone, the primary male sex hormone, are associated with increased risk of cardiovascular calcification, whilst estrogen, the primary female sex hormone, is considered cardioprotective. Current understanding of sexual dimorphism in cardiovascular calcification is still very limited. This review assesses the evidence that the actions of sex hormones influence the development of cardiovascular calcification. We address the current question of whether sex hormones could play a role in the sexual dimorphism seen in cardiovascular calcification, by discussing potential mechanisms of actions of sex hormones and evidence in pre-clinical research. More advanced investigations and understanding of sex hormones in calcification could provide a better translational outcome for those suffering with cardiovascular calcification.

Role of sex hormones in lung cancer

2021 ◽  
pp. 153537022110196
Author(s):  
Nathalie Fuentes ◽  
Miguel Silva Rodriguez ◽  
Patricia Silveyra
Keyword(s):  
Lung Cancer ◽  
Sex Differences ◽  
Sex Hormones ◽  
Hormone Receptors ◽  
Occupational Exposures ◽  
Lung Carcinogenesis ◽  
Male And Female ◽  
Female Sex ◽  
Incidence And Mortality ◽  
Cancer Rates

Lung cancer represents the world’s leading cause of cancer deaths. Sex differences in the incidence and mortality rates for various types of lung cancers have been identified, but the biological and endocrine mechanisms implicated in these disparities have not yet been determined. While some cancers such as lung adenocarcinoma are more commonly found among women than men, others like squamous cell carcinoma display the opposite pattern or show no sex differences. Associations of tobacco product use rates, susceptibility to carcinogens, occupational exposures, and indoor and outdoor air pollution have also been linked to differential rates of lung cancer occurrence and mortality between sexes. While roles for sex hormones in other types of cancers affecting women or men have been identified and described, little is known about the influence of sex hormones in lung cancer. One potential mechanism identified to date is the synergism between estrogen and some tobacco compounds, and oncogene mutations, in inducing the expression of metabolic enzymes, leading to enhanced formation of reactive oxygen species and DNA adducts, and subsequent lung carcinogenesis. In this review, we present the literature available regarding sex differences in cancer rates, associations of male and female sex hormones with lung cancer, the influence of exogenous hormone therapy in women, and potential mechanisms mediated by male and female sex hormone receptors in lung carcinogenesis. The influence of biological sex on lung disease has recently been established, thus new research incorporating this variable will shed light on the mechanisms behind the observed disparities in lung cancer rates, and potentially lead to the development of new therapeutics to treat this devastating disease.

scholarly journals A novel homeostatic loop of sorcin drives paclitaxel-resistance and malignant progression via Smad4/ZEB1/miR-142-5p in human ovarian cancer

Oncogene ◽  
2021 ◽  
Author(s):  
Jinguo Zhang ◽  
Wencai Guan ◽  
Xiaolin Xu ◽  
Fanchen Wang ◽  
Xin Li ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Calcium Binding ◽  
Molecular Mechanisms ◽  
Epithelial Mesenchymal Transition ◽  
Malignant Progression ◽  
Bioinformatics Analyses ◽  
Aberrant Expression ◽  
Mesenchymal Transition ◽  
E Box

AbstractThe primary chemotherapy of ovarian cancer (OC) often acquires chemoresistance. Sorcin (SRI), a soluble resistance-related calcium-binding protein, has been reported to be an oncogenic protein in cancer. However, the molecular mechanisms of SRI regulation and the role and aberrant expression of SRI in chemoresistant OC remain unclear. Here, we identified SRI as a key driver of paclitaxel (PTX)-resistance and explored its regulatory mechanism. Using transcriptome profiles, qRT-PCR, proteomics, Western blot, immunohistochemistry, and bioinformatics analyses, we found that SRI was overexpressed in PTX-resistant OC cells and the overexpression of SRI was related to the poor prognosis of patients. SRI was a key molecule required for growth, migration, and PTX-resistance in vitro and in vivo and was involved in epithelial–mesenchymal transition (EMT) and stemness. Mechanistic studies showed that miR-142-5p directly bound to the 3ʹ-UTR of SRI to suppress its expression, whereas a transcription factor zinc-finger E-box binding homeobox 1 (ZEB1) inhibited the transcription of miR-142-5p by directly binding to the E-box fragment in the miR-142 promoter region. Furthermore, ZEB1 was negatively regulated by SRI which physically interacted with Smad4 to block its translocation from the cytosol to the nucleus. Taken together, our findings unveil a novel homeostatic loop of SRI that drives the PTX-resistance and malignant progression via Smad4/ZEB1/miR-142-5p in human OC. Targeting this SRI/Smad4/ZEB1/miR-142-5p loop may reverse the PTX-resistance.

scholarly journals Molecular mechanisms of cell death in neurological diseases

2021 ◽  
Author(s):  
Diane Moujalled ◽  
Andreas Strasser ◽  
Jeffrey R. Liddell
Keyword(s):  
Cell Death ◽  
Neurodegenerative Diseases ◽  
Molecular Mechanisms ◽  
Neuronal Development ◽  
Neurological Diseases ◽  
Treatment Strategies ◽  
Current Treatment ◽  
Response To Therapy ◽  
Signalling Cascades ◽  
The Brain

AbstractTightly orchestrated programmed cell death (PCD) signalling events occur during normal neuronal development in a spatially and temporally restricted manner to establish the neural architecture and shaping the CNS. Abnormalities in PCD signalling cascades, such as apoptosis, necroptosis, pyroptosis, ferroptosis, and cell death associated with autophagy as well as in unprogrammed necrosis can be observed in the pathogenesis of various neurological diseases. These cell deaths can be activated in response to various forms of cellular stress (exerted by intracellular or extracellular stimuli) and inflammatory processes. Aberrant activation of PCD pathways is a common feature in neurodegenerative diseases, such as amyotrophic lateral sclerosis (ALS), Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease, resulting in unwanted loss of neuronal cells and function. Conversely, inactivation of PCD is thought to contribute to the development of brain cancers and to impact their response to therapy. For many neurodegenerative diseases and brain cancers current treatment strategies have only modest effect, engendering the need for investigations into the origins of these diseases. With many diseases of the brain displaying aberrations in PCD pathways, it appears that agents that can either inhibit or induce PCD may be critical components of future therapeutic strategies. The development of such therapies will have to be guided by preclinical studies in animal models that faithfully mimic the human disease. In this review, we briefly describe PCD and unprogrammed cell death processes and the roles they play in contributing to neurodegenerative diseases or tumorigenesis in the brain. We also discuss the interplay between distinct cell death signalling cascades and disease pathogenesis and describe pharmacological agents targeting key players in the cell death signalling pathways that have progressed through to clinical trials.

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