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Biology of Sex Differences

Madhavi Pandya, Thulani H Palpagama, Clinton Turner, Henry J Waldvogel, Richard L Faull, Andrea Kwakowsky
Gamma-aminobutyric acid (GABA) is the primary inhibitory neurotransmitter in the nervous system. Previous studies have shown fluctuations in expression levels of GABA signaling components-glutamic acid decarboxylase (GAD), GABA receptor (GABAR) subunit, and GABA transporter (GAT)-with increasing age and between sexes; however, this limited knowledge is highly based on animal models that produce inconsistent findings. This study is the first analysis of the age- and sex-specific changes of the GAD, GABAA/B R subunits, and GAT expression in the human primary sensory and motor cortices; superior (STG), middle (MTG), and inferior temporal gyrus (ITG); and cerebellum...
January 14, 2019: Biology of Sex Differences
Dillion D Hutson, Rakesh Gurrala, Benard O Ogola, Margaret A Zimmerman, Ricardo Mostany, Ryousuke Satou, Sarah H Lindsey
BACKGROUND: Estrogen is formed by the enzyme aromatase (CYP19A1) and signals via three identified receptors ERα (ESR1), ERß (ESR2), and the G protein-coupled estrogen receptor (GPER). Understanding the relative contribution of each receptor to estrogenic signaling may elucidate the disparate effects of this sex hormone across tissues, and recent developments in PCR technology allow absolute quantification and direct comparison of multiple targets. We hypothesized that this approach would reveal tissue- and sex-specific differences in estrogen receptor mRNA...
January 11, 2019: Biology of Sex Differences
Jill B Becker, Carolyn M Mazure
The Fast-Track Action Committee on (the) Health Science and Technology Response to the Opioid Crisis recently released their draft report for public comment. This report provides the "roadmap" for a coordinated federal research and development response to the opioid crisis. Other than noting the important concerns regarding maternal and neonatal exposure to opioids, the report overlooks the laboratory, clinical, and epidemiological data that inform the need for further research on sex and gender differences in opioid addiction that have critical gender-based treatment and prevention implications...
January 7, 2019: Biology of Sex Differences
Shuchun Lin, Yun Liu, Lynn R Goldin, Chen Lyu, Xiangyin Kong, Yan Zhang, Neil E Caporaso, Song Xiang, Ying Gao
BACKGROUND: Men are at higher risk of developing chronic lymphocytic leukemia (CLL) than women. DNA methylation has been shown to play important roles in a number of cancers. There are differences in the DNA methylation pattern between men and women. In this study, we investigated whether this contributes to the sex-related difference of B cell CLL risk. METHODS: Using the HumanMethylation450 BeadChip, we profiled the genome-wide DNA methylation pattern of CD19+ B cells from 48 CLL patients (29 female patients and 19 male patients) and 28 healthy people (19 women and 9 men)...
January 7, 2019: Biology of Sex Differences
Eman Y Gohar, Anthony K Cook, David M Pollock, Edward W Inscho
BACKGROUND: The pathogenesis of hypertension is distinct between men and women. Endothelin-1 (ET-1) is a potential contributor to sex differences in the pathophysiology of hypertension. ET-1 participates in blood pressure regulation through activation of endothelin A (ETA ) and endothelin B (ETB ) receptors including those in the vasculature. Previous studies demonstrated that sex and sex hormones evoke discrepancies in ET-1-mediated control of vascular tone in different vascular beds...
January 3, 2019: Biology of Sex Differences
Liam J Ward, Patrik Olausson, Wei Li, Xi-Ming Yuan
BACKGROUND: Atherosclerotic lesions are comprised of distinct regions with different proteomic profiles. Men and women develop differences in lesion phenotype, with lesions from women generally being more stable and less prone to rupture. We aimed to investigate the differences in proteomic profiles between sexes, including distinct lesion regions, to identify altered proteins that contribute to these differences observed clinically. METHODS: Carotid endarterectomy samples (ten men/ten women) were obtained, and intraplaque biopsies from three distinct regions (internal control, fatty streak and plaque) were analysed by tandem-mass spectrometry...
December 29, 2018: Biology of Sex Differences
Jane F Reckelhoff, Barbara T Alexander
In 2016, the National Institutes of Health mandated that all grant proposals enhance reproducibility through rigor and transparency. In the past few years, physiological outcomes in established animal models of hypertension, in particular in regard to sex differences, have varied from study to study or laboratory to laboratory. The aim of this commentary is to increase investigator awareness of caveats related to animal models that may be sensitive to vendor-, barrier-, or diet-specific changes that result in an inability to sustain the genotype and/or phenotype of well-established experimental models...
December 22, 2018: Biology of Sex Differences
Mi-Na Kim, Seong-Mi Park, Dong-Hyuk Cho, Hack-Lyoung Kim, Mi-Seung Shin, Myung-A Kim, Kyung-Soon Hong, Wan-Joo Shim
BACKGROUND: Evidence suggests that epicardial adipose tissue (EAT) is closely related to coronary artery stenosis (CAS). However, sexual dimorphism may be present in adipose tissue, and its influence on CAS between men and women is controversial. We assessed the relationship between EAT and CAS by sex and menopausal status in patients with suspected angina. METHODS: Six hundred twenty-eight consecutive patients (men/women n = 257/371; mean age = 59.9 ± 10...
December 14, 2018: Biology of Sex Differences
Tiewei Li, Fang Wang, Rui Peng, Shengqiang Pei, Zhihui Hou, Bin Lu, Xiangfeng Cong, Xi Chen
BACKGROUND: Plasma fibrinogen (FIB) has been demonstrated to be a risk factor for cardiovascular disease. Patients with non-calcified plaque (NCP) or mix plaque (MP) have a higher risk of poor outcomes. However, the association between FIB and the presence of NCP or MP (NCP/MP) remains unclear, and if present, whether sex has any impact on this association remains unknown. The aim of this study was to investigate the role of FIB in predicting the presence of NCP/MP and evaluate whether sex has any impact on this association...
December 5, 2018: Biology of Sex Differences
Żaneta Piotrowska, Michał Niezgoda, Wojciech Łebkowski, Anna Filipek, Natalia Domian, Irena Kasacka
BACKGROUND: Women live about 4 years longer due to lower prevalence of cardiovascular complication with ageing. However, the mechanisms involved in the preservation of heart functionality in women have not been fully elucidated. The endocannabinoid system fulfils a significant role in the regulation of cardiovascular system functioning. Cannabinoids, acting through specific receptors (CB1 and CB2), influence on blood pressure, heart rate and myocardial contractility. The function of cardiac muscle cells is strictly dependent on calcium ions...
November 27, 2018: Biology of Sex Differences
Sreenivasan Paruthiyil, Shin-Ichiro Hagiwara, Keshav Kundassery, Aditi Bhargava
BACKGROUND: Chronic stress is a major contributor in the development of metabolic syndrome and associated diseases, such as diabetes. High-fat diet (HFD) and sex are known modifiers of metabolic parameters. Peptide hormones corticotropin-releasing factor (CRF) and urocortins (UCN) mediate stress responses via activation and feedback to the hypothalamic-pituitary-adrenal (HPA) axis. UCN3 is a marker of pancreatic β-cell differentiation, and UCN2 is known to ameliorate glucose levels in mice rendered diabetic with HFD...
November 6, 2018: Biology of Sex Differences
Andrea Iorga, Soban Umar, Gregoire Ruffenach, Laila Aryan, Jingyuan Li, Salil Sharma, Negar Motayagheni, Rangarajan D Nadadur, Jean C Bopassa, Mansoureh Eghbali
BACKGROUND: Recently, we showed that exogenous treatment with estrogen (E2) rescues pre-existing advanced heart failure (HF) in mice. Since most of the biological actions of E2 are mediated through the classical estrogen receptors alpha (ERα) and/or beta (ERβ), and both these receptors are present in the heart, we examined the role of ERα and ERβ in the rescue action of E2 against HF. METHODS: Severe HF was induced in male mice by transverse aortic constriction-induced pressure overload...
October 30, 2018: Biology of Sex Differences
Zeyneb Kurt, Rio Barrere-Cain, Jonnby LaGuardia, Margarete Mehrabian, Calvin Pan, Simon T Hui, Frode Norheim, Zhiqiang Zhou, Yehudit Hasin, Aldons J Lusis, Xia Yang
BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) encompasses benign steatosis and more severe conditions such as non-alcoholic steatohepatitis (NASH), cirrhosis, and liver cancer. This chronic liver disease has a poorly understood etiology and demonstrates sexual dimorphisms. We aim to examine the molecular mechanisms underlying sexual dimorphisms in NAFLD pathogenesis through a comprehensive multi-omics study. We integrated genomics (DNA variations), transcriptomics of liver and adipose tissue, and phenotypic data of NAFLD derived from female mice of ~ 100 strains included in the hybrid mouse diversity panel (HMDP) and compared the NAFLD molecular pathways and gene networks between sexes...
October 22, 2018: Biology of Sex Differences
Benjamin Abelson, Daniel Sun, Lauren Que, Rebecca A Nebel, Dylan Baker, Patrick Popiel, Cindy L Amundsen, Toby Chai, Clare Close, Michael DiSanto, Matthew O Fraser, Stephanie J Kielb, George Kuchel, Elizabeth R Mueller, Mary H Palmer, Candace Parker-Autry, Alan J Wolfe, Margot S Damaser
Females and males differ significantly in gross anatomy and physiology of the lower urinary tract, and these differences are commonly discussed in the medical and scientific literature. However, less attention is dedicated to investigating the varied development, function, and biology between females and males on a cellular level. Recognizing that cell biology is not uniform, especially in the lower urinary tract of females and males, is crucial for providing context and relevance for diverse fields of biomedical investigation...
October 22, 2018: Biology of Sex Differences
Helena Bergström, Elsa Brånvall, Maria Helde-Frankling, Linda Björkhem-Bergman
BACKGROUND: Statins are often discontinued in patients with advanced cancer since the net effect of treatment is considered negative. However, guidelines concerning discontinuation of statin treatment are lacking. The aim of this study was to investigate any differences in time of discontinuation of statin treatment between men and women with advanced cancer disease. METHODS: Medical records from 195 deceased palliative cancer patients from a previous study cohort were reviewed...
October 20, 2018: Biology of Sex Differences
Wenling Tan, Adiilah K Soodeen-Lalloo, Yue Chu, Weijie Xu, Fengfang Chen, Jie Zhang, Wei Sha, Jin Huang, Guanghong Yang, Lianhua Qin, Jie Wang, Xiaochen Huang, Jingyun Shi, Yonghong Feng
BACKGROUND: Worldwide tuberculosis (TB) reports show a male bias in morbidity; however, the differences in pathogenesis between men and women with TB, as well as the mechanisms associated with such differences, are poorly investigated. We hypothesized that comparison of the degree of lung injury and clinical indices of well-matched men and women with newly diagnosed TB, and statistical analysis of the correlation between these indices and the extent of lung lesions, can provide insights into the mechanism of gender bias in TB...
October 10, 2018: Biology of Sex Differences
Kimia Sobhani, Diana K Nieves Castro, Qin Fu, Roberta A Gottlieb, Jennifer E Van Eyk, C Noel Bairey Merz
Since 1984, each year, more women than men die of ischemic heart disease (IHD) and heart failure (HF), yet more men are diagnosed. Because biomarker assessment is often the first diagnostic employed in such patients, understanding biomarker differences in men vs. women may improve female morbidity and mortality rates.Some key examples of cardiac biomarker utility based on sex include contemporary use of "unisex" troponin reference intervals under-diagnosing myocardial necrosis in women; greater use of hsCRP in the setting of acute coronary syndrome (ACS) could lead to better stratification in women; and greater use of BNP with sex-specific thresholds in ACS could also lead to more timely risk stratification in women...
September 17, 2018: Biology of Sex Differences
Abdulaziz Awali, Ali M Alsouhibani, Marie Hoeger Bement
BACKGROUND: Previous studies have shown that women experience greater temporal summation (TS) of pain than men using a repetitive thermal stimulus. These studies, however, did not individualize the thermal stimulus to each subject's thermal pain sensitivity. The aim of this study was to investigate sex differences in TS using an individualized protocol and potential mediators that have been shown to influence TS including physical activity and body composition. METHODS: Fifty young healthy men and women (21 men) participated in the study...
September 15, 2018: Biology of Sex Differences
Scott Fuller, Yongmei Yu, Tamra Mendoza, David M Ribnicky, William T Cefalu, Z Elizabeth Floyd
BACKGROUND: Insulin resistance underlies metabolic syndrome and is associated with excess adiposity and visceral fat accumulation, which is more frequently observed in males than females. However, in young females, the prevalence of metabolic syndrome is rising, mainly driven by accumulation of abdominal visceral fat. The degree to which sex-related differences could influence the development of insulin resistance remains unclear, and studies of potential therapeutic strategies to combat metabolic syndrome using rodent models have focused predominantly on males...
September 12, 2018: Biology of Sex Differences
Qingming Dong, Michael S Kuefner, Xiong Deng, Dave Bridges, Edwards A Park, Marshall B Elam, Rajendra Raghow
BACKGROUND: Patients with metabolic syndrome, who are characterized by co-existence of insulin resistance, hypertension, hyperlipidemia, and obesity, are also prone to develop non-alcoholic fatty liver disease (NAFLD). Although the prevalence and severity of NAFLD is significantly greater in men than women, the mechanisms by which gender modulates the pathogenesis of hepatic steatosis are poorly defined. The obese spontaneously hypertensive (SHROB) rats represent an attractive model of metabolic syndrome without overt type 2 diabetes...
September 10, 2018: Biology of Sex Differences
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