Sex differences in metabolic homeostasis, diabetes, and obesity
Abstract There are fundamental aspects of the control of metabolic homeostasis that are regulated differently in males and females. This sex asymmetry represents an evolutionary paradigm for females to resist the loss of energy stores. This perspective discusses the most fundamental sex differences in metabolic homeostasis, diabetes, and obesity. Together, the role of genetic sex, the programming effect of testosterone in the prenatal period in males, and the activational role of sex hormones at puberty produce two different biological systems in males and females that need to be studied separately. These sex-spe...
Source: Biology of Sex Differences - September 3, 2015 Category: Biology Source Type: research

Sex differences in the brain: a whole body perspective
Abstract Most writing on sexual differentiation of the mammalian brain (including our own) considers just two organs: the gonads and the brain. This perspective, which leaves out all other body parts, misleads us in several ways. First, there is accumulating evidence that all organs are sexually differentiated, and that sex differences in peripheral organs affect the brain. We demonstrate this by reviewing examples involving sex differences in muscles, adipose tissue, the liver, immune system, gut, kidneys, bladder, and placenta that affect the nervous system and behavior. The second consequence of ignoring other...
Source: Biology of Sex Differences - August 15, 2015 Category: Biology Source Type: research

Sex differences in gut fermentation and immune parameters in rats fed an oligofructose-supplemented diet
Conclusions We have shown that male and female rat gut communities metabolize an OF-supplemented diet differently. Sex-specific responses in both the fecal community and systemic immune parameters suggest that this difference may result from an increase in the availability of gut peptidyl-nitrogen in the males. These findings demonstrate the importance of performing sex-comparative studies when investigating potential health effects of prebiotics using rodent models. (Source: Biology of Sex Differences)
Source: Biology of Sex Differences - August 6, 2015 Category: Biology Source Type: research

Exogenous 17-β estradiol administration blunts progression of established angiotensin II-induced abdominal aortic aneurysms in female ovariectomized mice
Conclusions E2 administration to Ovx females abolished progressive growth and decreased severity of AngII-induced AAAs. These effects were accompanied by increased SMC α-actin, elevated TGF-β, and reduced neutrophils. Similarly, E2 administration reduced AngII-induced atherosclerosis. These results suggest that loss of E2 in post-menopausal females may contribute to progressive growth of AAAs. (Source: Biology of Sex Differences)
Source: Biology of Sex Differences - June 29, 2015 Category: Biology Source Type: research

Sex differences of leukocytes DNA methylation adjusted for estimated cellular proportions
Abstract Background DNA methylation, which is most frequently the transference of a methyl group to the 5-carbon position of the cytosine in a CpG dinucleotide, plays an important role in both normal development and diseases. To date, several genome-wide methylome studies have revealed sex-biased DNA methylation, yet no studies have investigated sex differences in DNA methylation by taking into account cellular heterogeneity. The aim of the present study was to investigate sex-biased DNA methylation on the autosomes in human blood by adjusting for estimated cellular proportions because cell...
Source: Biology of Sex Differences - June 25, 2015 Category: Biology Source Type: research

Age- and sex-specific differences in blood-borne microvesicles from apparently healthy humans
This study identified cellular origin of blood-borne MV>0.2 μm in blood of apparently healthy women and men aged from 20–70 years. Methods Venous blood from apparently healthy participants in the Mayo Clinic Biobank was collected into tubes containing protease inhibitors as the anticoagulant. MV were isolated by standardized differential centrifugation and characterized by digital flow cytometer. Each cellular origin of MV was verified by two different antibodies with strong correlation between the two distinct antibodies (e.g., for platelet-derived MV, r ...
Source: Biology of Sex Differences - May 11, 2015 Category: Biology Source Type: research

Testosterone modulates cardiac contraction and calcium homeostasis: cellular and molecular mechanisms
Abstract The incidence of cardiovascular disease rises dramatically with age in both men and women. Because a woman’s risk of cardiovascular disease rises markedly after the onset of menopause, there has been growing interest in the effect of estrogen on the heart and its role in the pathophysiology of these diseases. Much less attention has been paid to the impact of testosterone on the heart, even though the levels of testosterone also decline with age and low-testosterone levels are linked to the development of cardiovascular diseases. The knowledge that receptors for all major sex steroid hormones, incl...
Source: Biology of Sex Differences - April 29, 2015 Category: Biology Source Type: research

Neural growth hormone: regional regulation by estradiol and/or sex chromosome complement in male and female mice
Conclusions Sex chromosome complement regulates GH in some but not all brain areas, and within the hypothalamus, sex chromosomes have cell-specific actions on GH. Thus, sex chromosome complement and estradiol both contribute to GH sex differences in the brain. (Source: Biology of Sex Differences)
Source: Biology of Sex Differences - April 28, 2015 Category: Biology Source Type: research

Estrogens increase expression of bone morphogenetic protein 8b in brown adipose tissue of mice
Conclusions BAT Bmp8b expression in mice is positively regulated by presence of ovaries and estrogens such as DES. (Source: Biology of Sex Differences)
Source: Biology of Sex Differences - April 3, 2015 Category: Biology Source Type: research

Y genetic variation and phenotypic diversity in health and disease
Abstract Sexually dimorphic traits arise through the combined effects of sex hormones and sex chromosomes on sex-biased gene expression, and experimental mouse models have been instrumental in determining their relative contribution in modulating sex differences. A role for the Y chromosome (ChrY) in mediating sex differences outside of development and reproduction has historically been overlooked due to its unusual genetic composition and the predominant testes-specific expression of ChrY-encoded genes. However, ample evidence now exists supporting ChrY as a mediator of other physiological traits in males, and g...
Source: Biology of Sex Differences - March 13, 2015 Category: Biology Source Type: research

The evolution of sex differences in disease
Abstract It is now becoming widely recognized that there are important sex differences in disease. These include rates of disease incidence, symptoms and age of onset. These differences between the sexes can be seen as a subset of the more general phenomenon of sexual dimorphism of quantitative phenotypes. From a genetic point of view, this is paradoxical, since the vast majority of genetic material is shared between the sexes. How can males and females differ in so many ways and yet have a common genetic code? Traditionally, the modifying action of hormones has been offered as a solution to this paradox, but exp...
Source: Biology of Sex Differences - March 13, 2015 Category: Biology Source Type: research

Expression of drug transporters in human kidney: impact of sex, age, and ethnicity
Abstract Background Differences in expression of drug transporters in human kidney contribute to changes in pharmacokinetics and toxicokinetics of a variety of drug compounds. The basal expression levels of genes involved in drug transport processes in the kidney introduces differences in bioavailability, distribution, and clearance of drugs, possibly influencing drug efficacy and adverse reactions. Sex differences in gene expression of transporters are a key cause of differences in sex-dependent pharmacokinetics, which may characterize many drugs and contribute to individual differences in...
Source: Biology of Sex Differences - March 2, 2015 Category: Biology Source Type: research

Early androgen exposure and human gender development
This article critically reviews the available evidence regarding influences of testosterone on human gender-related development. In humans, testosterone is elevated in males from about weeks 8 to 24 of gestation and then again during early postnatal development. Individuals exposed to atypical concentrations of testosterone or other androgenic hormones prenatally, for example, because of genetic conditions or because their mothers were prescribed hormones during pregnancy, have been consistently found to show increased male-typical juvenile play behavior, alterations in sexual orientation and gender identity (the sense of ...
Source: Biology of Sex Differences - February 26, 2015 Category: Biology Source Type: research

Extracellular vesicles in urine of women with but not without kidney stones manifest patterns similar to men: a case control study
This study was designed to standardize methodology to characterize urinary EVs by digital flow cytometry and to identify possible sex differences in EVs in persons with and without their first symptomatic kidney stones. Methods Twenty-four-hour urine collections were obtained from persons presenting with their first kidney stone episode (n = 50 women, 60 men; age 19–76 years) and sex- and age-matched controls from the general population (n = 24 women, 36 men). Results Standardization: Size ...
Source: Biology of Sex Differences - February 24, 2015 Category: Biology Source Type: research

Age and sex differences in kidney microRNA expression during the life span of F344 rats
In this study, we characterized the global kidney miRNA expression profile in untreated male and female F344 rats throughout the life span. These findings were correlated with sex-specific susceptibilities to adverse renal events, such as male-biased renal fibrosis and inflammation in old age. Methods Kidney miRNA expression was examined in F344 rats at 2, 5, 6, 8, 15, 21, 78, and 104 weeks of age in both sexes using Agilent miRNA microarrays. Differential expression was determined using filtering criteria of ≥1.5 fold change and ANOVA or pairwise t-test (FDR
Source: Biology of Sex Differences - January 28, 2015 Category: Biology Source Type: research

Human umbilical endothelial cells (HUVECs) have a sex: characterisation of the phenotype of male and female cells
Conclusions The results indicate that sex differences exist in prenatal life and are parameter-specific, suggesting that HUVECs of both sexes should be used as an in vitro model to increase the quality and the translational value of research. The sex differences observed in HUVECs could be relevant in explaining the diseases of adulthood because endothelial dysfunction has a crucial role in the pathogenesis of cardiovascular diseases, diabetes mellitus, neurodegeneration and immune disease. (Source: Biology of Sex Differences)
Source: Biology of Sex Differences - December 14, 2014 Category: Biology Source Type: research

Sex differences in mood disorders: perspectives from humans and rodent models
Abstract Mood disorders are devastating, often chronic illnesses characterized by low mood, poor affect, and anhedonia. Notably, mood disorders are approximately twice as prevalent in women compared to men. If sex differences in mood are due to underlying biological sex differences, a better understanding of the biology is warranted to develop better treatment or even prevention of these debilitating disorders. In this review, our goals are to: 1) summarize the literature related to mood disorders with respect to sex differences in prevalence, 2) introduce the corticolimbic brain network of mood regulation, 3) di...
Source: Biology of Sex Differences - December 7, 2014 Category: Biology Source Type: research

Examination of the genetic basis for sexual dimorphism in the Aedes aegypti (dengue vector mosquito) pupal brain
Conclusions These studies revealed sex-specific gene expression profiles in the developing A. aegypti pupal head and identified Doublesex as a key regulator of sexually dimorphic gene expression during mosquito neural development. (Source: Biology of Sex Differences)
Source: Biology of Sex Differences - October 21, 2014 Category: Biology Source Type: research

Effects of sex chromosome dosage on corpus callosum morphology in supernumerary sex chromosome aneuploidies
Conclusions Our results suggest that X- and Y-linked genes have differential effects on CC morphometry. To our knowledge, this is the first study to compare CC morphometry across these extremely rare groups. (Source: Biology of Sex Differences)
Source: Biology of Sex Differences - October 16, 2014 Category: Biology Source Type: research

NIH initiative to balance sex of animals in preclinical studies: generative questions to guide policy, implementation, and metrics
Abstract In May of 2014, the NIH Director together with the Director of the Office of Research on Women’s Health announced plans to take a multi-dimensional approach to address the over reliance on male cells and animals in preclinical research. The NIH is engaging the scientific community in the development of policies to improve the sex balance in research. The present, past, and future presidents of the Organization for the Study of Sex Differences, in order to encourage thoughtful discussion among scientists, pose a series of questions to generate ideas in three areas: 1. research strategies, 2. educati...
Source: Biology of Sex Differences - October 3, 2014 Category: Biology Source Type: research

Estrogen receptor beta and truncated variants enhance the expression of transfected MMP-1 promoter constructs in response to specific mechanical loading
Conclusions These results suggest that the 1G/2G alleles of MMP-1 are influenced by specific mechanical stimuli like shear stress, as well as the ER-β receptor. These findings contribute to the potential allelic involvement in connective tissue diseases such as OA in females compared to males. (Source: Biology of Sex Differences)
Source: Biology of Sex Differences - September 27, 2014 Category: Biology Source Type: research

Pressor responsiveness to angiotensin II in female mice is enhanced with age: role of the angiotensin type 2 receptor
Conclusions The protective role of the AT2R depressor pathway is lost with age in female mice. Therefore, targeting deficits in AT2R expression and/or signaling may represent a novel anti-hypertensive approach in aged females. (Source: Biology of Sex Differences)
Source: Biology of Sex Differences - September 16, 2014 Category: Biology Source Type: research

Effects of age and sex on cerebrovascular function in the rat middle cerebral artery
Conclusions This is the first study to examine the effects of age and sex on the mechanisms underlying cerebrovascular reactivity to VP. Interestingly, VP-mediated constriction was reduced by age in F, but was unchanged in M rats. Additionally, it was observed that selective blockade of COX-1 or COX-2 produced age-dependent changes in cerebrovascular reactivity to VP and that VP-stimulated PGI2 and TXA2 production were enhanced by endogenous estrogen in younger F. A better understanding of the mechanisms by which estrogen exerts its effects may lead to new age- and sex-specific therapeutic agents for the prevent...
Source: Biology of Sex Differences - September 11, 2014 Category: Biology Source Type: research

Sexually dimorphic characteristics of the small intestine and colon of prepubescent C57BL/6 mice
Conclusions This study reveals molecular dissimilarities between males and females in the small intestine and colon of prepubescent mice, which might underlie differences in physiological functioning and in disease predisposition in the two sexes. (Source: Biology of Sex Differences)
Source: Biology of Sex Differences - August 29, 2014 Category: Biology Source Type: research

rLOAD: does sex mediate the effect of acute antiplatelet loading on stroke outcome
Abstract Background Biologic sex can influence response to pharmacologic therapy. The purpose of this proof-of-concept study was to evaluate the medicating effects of estrogen in the efficacy of acute antiplatelet loading therapy on stroke outcome in the rabbit small clot embolic model. Methods Female and male (20/group) New Zealand White rabbits were embolized to produce embolic stroke by injecting small blood clots into the middle cerebral artery via an internal carotid artery catheter. Two hours after embolization, rabbits were treated with sta...
Source: Biology of Sex Differences - July 15, 2014 Category: Biology Source Type: research

The effects of perinatal testosterone exposure on the DNA methylome of the mouse brain are late-emerging
Conclusion Taken together, our data imply that the organizational effects of testosterone on the brain methylome and transcriptome are dramatic and late-emerging. Our findings offer important insights into the long-term molecular effects of early-life hormonal exposure. (Source: Biology of Sex Differences)
Source: Biology of Sex Differences - June 13, 2014 Category: Biology Source Type: research

GenderMedDB: an interactive database of sex and gender-specific medical literature
Conclusions Overall, GenderMedDB offers the advantages of a discipline-specific search engine as well as the functions of a participative tool for the gender medicine community. (Source: Biology of Sex Differences)
Source: Biology of Sex Differences - May 23, 2014 Category: Biology Source Type: research

Estrogen regulation of protein expression and signaling pathways in the heart
Abstract Sex differences in cardiovascular disease and cardiac physiology have been reported in humans as well as in animal models. Premenopausal women have reduced cardiovascular disease compared to men, but the incidence of cardiovascular disease in women increases following menopause. Sex differences in cardiomyocytes likely contribute to the differences in male–female physiology and response to disease. Sex differences in the heart have been noted in electrophysiology, contractility, signaling, metabolism, and cardioprotection. These differences appear to be due, at least in part, to differences in gene...
Source: Biology of Sex Differences - March 10, 2014 Category: Biology Source Type: research

Transcriptional effects of gene dose reduction
Abstract Large-scale gene dose reductions usually lead to abnormal phenotypes or death. However, male mammals, Drosophila, and Caenorhabditis elegans have only one X chromosome and thus can be considered as monosomic for a major chromosome. Despite the deleterious effects brought about by such gene dose reduction in the case of an autosome, X chromosome monosomy in males is natural and innocuous. This is because of the nearly full transcriptional compensation for X chromosome genes in males, as opposed to no or partial transcriptional compensation for autosomal one-dose genes arising due to deletions. Buffering, ...
Source: Biology of Sex Differences - March 3, 2014 Category: Biology Source Type: research

Sex differences in a mouse model of multiple sclerosis: neuropathic pain behavior in females but not males and protection from neurological deficits during proestrus
Conclusions We conclude that female mice are superior to males for the study of neuropathic pain-like behaviors associated with MOG35-55-induced EAE. Further, proestrus may be protective against EAE-induced neurological deficits, thus necessitating further investigation into the impact that estrous cycle exerts on MS symptoms. (Source: Biology of Sex Differences)
Source: Biology of Sex Differences - February 28, 2014 Category: Biology Source Type: research

Influence of sex differences on microRNA gene regulation in disease
Abstract Sexual dimorphism is observed in most human diseases. The difference in the physiology and genetics between sexes can contribute tremendously to the disease prevalence, severity, and outcome. Both hormonal and genetic differences between males and females can lead to differences in gene expression patterns that can influence disease risk and course. MicroRNAs have emerged as potential regulatory molecules in all organisms. They can have a broad effect on every aspect of physiology, including embryogenesis, metabolism, and growth and development. Numerous microRNAs have been identified and elucidated to p...
Source: Biology of Sex Differences - February 1, 2014 Category: Biology Source Type: research

Sex-biased chromatin and regulatory cross-talk between sex chromosomes, autosomes, and mitochondria
Abstract Several autoimmune and neurological diseases exhibit a sex bias, but discerning the causes and mechanisms of these biases has been challenging. Sex differences begin to manifest themselves in early embryonic development, and gonadal differentiation further bifurcates the male and female phenotypes. Even at this early stage, however, there is evidence that males and females respond to environmental stimuli differently, and the divergent phenotypic responses may have consequences later in life. The effect of prenatal nutrient restriction illustrates this point, as adult women exposed to prenatal restrictio...
Source: Biology of Sex Differences - January 15, 2014 Category: Biology Source Type: research

Coronary vessels and cardiac myocytes of middle-aged rats demonstrate regional sex-specific adaptation in response to postmyocardial infarction remodeling
Abstract Background An increasing body of evidence indicates that left ventricular (LV) remodeling, especially the degree of reactive myocardial hypertrophy after myocardial infarction (MI), differs in males and females. Surprisingly, to date, the sex-specific post-MI alterations of the coronary vasculature remain undetermined. Therefore, we tested the hypothesis that adaptive coronary arteriolar and capillary modifications occurring in response to reactive myocyte hypertrophy differ between middle-aged male and female post-MI rats. Methods A larg...
Source: Biology of Sex Differences - January 3, 2014 Category: Biology Source Type: research

A comparative study of renal function in male and female spiny mice – sex specific responses to a high salt challenge
Abstract Background There is a significant body of evidence to suggest that hormone levels, receptor density and structural differences between males and females can significantly alter renal hemodynamics. We compared the renal hemodynamic and excretory profile of female and male spiny mice under baseline conditions and in response to a high-NaCl diet. Methods Adult male and female spiny mice were fed either a normal or high salt diet for 7 days. Renal excretory profile was obtained from 24 h urine samples, and renal hemodynamic measurements using...
Source: Biology of Sex Differences - December 10, 2013 Category: Biology Source Type: research

Sex chromosome complement regulates expression of mood-related genes
Conclusions Under chronic stress conditions, sex-related factors differentially influence expression of genes linked to mood regulation in the frontal cortex. The main factor influencing expression of GABA-, serotonin-, and dopamine-related genes was sex chromosome complement, with an unexpected pro-disease effect in XY mice relative to XX mice. This effect was partially opposed by gonadal sex and circulating testosterone, although all three factors influenced signal transduction pathways in males. Since GABA, serotonin, and dopamine changes are also observed in other psychiatric and neurodegenerative disorders,...
Source: Biology of Sex Differences - November 7, 2013 Category: Biology Source Type: research

Anti-Müllerian hormone may regulate the number of calbindin-positive neurons in the sexually dimorphic nucleus of the preoptic area of male mice
Conclusions The establishment of dimorphic cell number in the CALB-SDN of mice is biphasic, with each phase being subject to different regulation. The second phase of dimorphism is not dependent on the first phase having occurred as it was present in the Amh -/- male mice that have female-like numbers of calbindin+ve neurons at 20 days. These observations extend emerging evidence that the organisation of highly dimorphic neuronal networks changes during puberty or afterwards. They also raise the possibility that cellular events attributed to the imprinting effects of testos...
Source: Biology of Sex Differences - October 11, 2013 Category: Biology Source Type: research

Sex differences in the prognostic significance of KRAS codons 12 and 13, and BRAF mutations in colorectal cancer: a cohort study
Conclusions Results from this cohort study demonstrate sex-related differences in the prognostic value of BRAF mutations in colorectal cancer, being particularly evident in men. These findings are novel and merit further validation. (Source: Biology of Sex Differences)
Source: Biology of Sex Differences - September 10, 2013 Category: Biology Source Type: research

Sex and inflammation in respiratory diseases: a clinical viewpoint
Abstract This review discusses sex differences in the prognosis of acute or chronic inflammatory diseases. The consequences of severe inflammation vary in relation to sex, depending on illness duration. In the majority of acute diseases, males present higher mortality rates, whereas continuous chronic inflammation associated with tissue damage is more deleterious in females. The recruitment of cells, along with its clinical expression, is more significant in females, as reflected by higher inflammatory markers. Given that estrogens or androgens are known to modulate inflammation, their different levels in males a...
Source: Biology of Sex Differences - September 1, 2013 Category: Biology Source Type: research

The Sex Chromosome Trisomy mouse model of XXY and XYY: metabolism and motor performance
Conclusions We find that the new SCT mouse model for XXY and XYY recapitulates features found in humans with these aneuploidies. We illustrate that this model has significant promise for unveiling the role of genetic effects compared to hormonal effects in these syndromes, because many phenotypes are different in XXY vs. XY gonadal female mice which have never been exposed to testicular secretions. (Source: Biology of Sex Differences)
Source: Biology of Sex Differences - August 8, 2013 Category: Biology Source Type: research

Sex differences in kidney gene expression during the life cycle of F344 rats
Conclusions These data represent one of the most comprehensive in-life time course studies to be published, assessing sex differences in global gene expression in the F344 rat kidney. PCA and Venn analyses reveal specific periods of sexually dimorphic gene expression which are associated with functional categories (xenobiotic metabolism and immune cell and inflammatory responses) of key relevance to acute kidney injury and chronic kidney disease, which may underlie sex-specific susceptibility. Analysis of the basal gene expression patterns of renal genes throughout the life cycle of the rat will improve the use ...
Source: Biology of Sex Differences - July 31, 2013 Category: Biology Source Type: research

Sex and the basic scientist: is it time to embrace Title IX?
(Source: Biology of Sex Differences)
Source: Biology of Sex Differences - July 27, 2013 Category: Biology Source Type: research

Growth hormone exacerbates diabetic renal damage in male but not female rats
Conclusions These studies indicate that GH affects renal injury in diabetes in a sex-specific manner and is associated with an increase in pro-inflammatory mediators. (Source: Biology of Sex Differences)
Source: Biology of Sex Differences - June 27, 2013 Category: Biology Source Type: research