Sex-dependent differences in prevalence and severity are characteristics of Alzheimer's disease (AD). Using the 3×Tg-AD mouse model, we previously reported that adult males show early behavioral dysfunction, altered epigenetic factors and lack of plaque/tangle pathology. Conversely, adult females retain more severe AD-like pathology and behavior. The present study examines whether gonadal hormones play a role in these differences in current cohorts of 3×Tg-AD mice.

Up to 80% of Alzheimer's disease (AD) patients suffer from brain vascular damage resulting in multi-etiology dementia (MED). Sex is a well-known risk factor for dementia; out of three AD patients two are women. 17β-estradiol, a predominant ovarian hormone in woman before menopause, is known to have beneficial effects on the cerebrovasculature, neuroinflammation and neuroprotection. Here, we investigated the consequences of the loss of ovarian hormones caused by surgical menopause (ovariectomy) on AD and MED.

Gestational environmental perturbations can induce sex-specific developmental programming, increasing offspring susceptibility to chronic diseases. While prenatal high estradiol (HE) exposure has been associated with male-biased neurodevelopmental disorders, the underlying mechanisms remain poorly understood.

Selective serotonin reuptake inhibitors are widely prescribed during pregnancy. Their main route of administration is through the gut. However, their impact on the maternal and offspring gut microbiome and microbial metabolic pathways remains poorly understood. This study used metagenomic shotgun sequencing to examine the effects of perinatal citalopram exposure in rat dams and their offspring on gut composition and downstream metabolic pathways.

Sexual dimorphism has been implied to certain human physiology and diseases. This topic has recently garnered more attention, highlighting individual variances in precision medicine and individualized clinical trials. It is recognized that individual gene expression variations in males and females could have profound physiological impacts. Tissue specific expression profiles determine protein-coding gene activities and contribute additional physiological variations. Therefore, tissue specific gene expression profiles should be comprehensively analyzed among individual human subjects. In this report, we developed a user-friendly bioinformatic tool to visualize gene expression levels and variances across tissue samples, aiming to facilitate research into potential sexual dimorphism genes. The Gini coefficient metric was used with the most recent GTEx V10 datasets to examine variations in the expression profiles of human protein-coding genes across 43 tissue subtypes. Next, these variations were specifically evaluated using the Gini coefficient index for male and female individuals across all tissue subtypes. Our web-based visualization tool generated tissue specific expression profiles for individual male and female samples. It concurrently illustrates expression levels and variation comparisons between male and female groups across all tissue subtypes. Although most protein-coding genes had similar expression variation patterns between the two sexes, several genes exhibited distinct variations for some tissue subtypes, as indicated by their significant Z-scores in Gini index disparities. Users can explore differentially expressed protein-coding genes across tissue subtypes or search for genes of interest in the Tissue Prominent Sexual Dimorphism Gene database (https://tpsdg.ibms.sinica.edu.tw). This database can be employed to visualize expression levels and variations among individual samples within specific tissues, thereby facilitating future research into divergently expressed protein-coding genes in the human population.

Despite growing recognition of sex differences in medicine, little is known about their role in neonatology, particularly among extremely premature infants (EPI, < 28 weeks gestation), who face high morbidity and mortality driven by infections. Antibiotics therapy is widely used but may alter cellular metabolism, leading to adverse drug reactions. However, pharmacological studies in EPI remain limited, and sex-dependent effects of antibiotic treatments are largely unexplored. This study investigated sex-related metabolomic differences in EPI in relation to antibiotic exposure.

Brain-derived neurotrophic factor (BDNF) is highly expressed in the hypothalamus where it exerts regulatory functions over neurogenesis, reproduction, energy balance, and metabolism. Analyzing a hypothalamic single-nucleus transcriptomic, we identified Fezf1 ventromedial hypothalamic (VMH) neurons as an important source of BDNF. During development, Fezf1 neurons are involved in the organization of the olfactory bulb, and mutations on this gene are responsible for Kallmann syndrome; however, in adult life, little is known about the functions of Fezf1 neurons.

Abdominal aortic aneurysm (AAA) is an abnormal dilation of the abdominal aorta that carries up to a 90% mortality rate when ruptured. Although male patients experience AAA at a higher rate than females, female patients experience AAA rupture at a rate three- to four-fold higher that of their male counterparts. The current standard clinicians use for determining when to surgically intervene is maximum transverse diameter of the AAA perpendicular to the axis of flow. However, some aneurysms below these diameter thresholds rupture. Machine learning (ML) classification models have been previously shown to predict patient outcomes with more discriminability than the diameter criterion. However, these models do not consider sex-based differences. In this proof-of-concept study, we investigate how creating sex-specific ML models impacts patient outcome prediction as compared to a general model encompassing all patients (sex agnostic).

Norepinephrine (noradrenaline; NE) is a stress signal released from the locus coeruleus (LC) into the prefrontal cortex (PFC) to govern arousal, attention, and cognition. The LC is sexually dimorphic, and PFC NE dysfunction contributes to alcohol use disorder and several stress-related neuropsychiatric disorders that manifest differently in men and women. However, most preclinical studies of the medial PFC (mPFC) NE system have only used male subjects. Additionally, even though each mPFC subregion and layer forms unique circuits that mediate different aspects of cognitive behavior, their specific neuromodulation by NE is not understood.

The term "metabolically healthy obesity" is used to define those patients with obesity that do not present elements of metabolic syndrome. The causes behind this temporary reduction of the cardiovascular risk are still unknown, although these patients are characterized by a conserved expansion capacity of the adipose tissue, preventing ectopic accumulation of fat. Since hormones are key regulators in adipogenesis, we hypothesize that there are sex-specific differences in visceral white adipose tissue (vWAT) biology that may contribute to metabolic health disparities between men and women.

Sex differences in exercise metabolism have been recognized for decades, but the molecular metabolic landscape in which men and women reach standardized physiological exhaustion criteria remains unexplored.

Drug metabolism va-specific dosing. Strychnine, the primary active compound in strychnine-based alkaloids, is used for treatment of hemiplegia or amblyopia. However, knowledge of sex-based difference in the pharmacokinetics of strychnine remains limited, increasing the risk of dosage error and potential toxicity in patient.ries between men and women derived from the difference in body fat distribution and hormone secretion, necessitating sex.

Cocaine-induced changes in nucleus accumbens shell (NAcSh) medium spiny neurons (MSNs) differ based on dopamine receptor subtype expression, the sex of the animal, and for females, phase of the estrous cycle. These findings highlight the need to account for both sex and estrous cycle when studying drug-mediated alterations in neurophysiology. Whether MSNs of the nucleus accumbens core (NAcC), which serve different aspects of reward function, will exhibit similar sex and estrous cycle effects with cocaine administration was investigated.

Maternal nutrient restriction (MNR) can increase maternal androgen concentrations during pregnancy and cause placental dysfunction leading to reduced fetal growth, especially in males. Placental androgen metabolism, as well as differential expression and subcellular localisation of androgen receptor (AR) variants, modulates androgen signalling, which may benefit placental function; however, the impact of MNR on these adaptations remains undefined. We characterised the impact of MNR and fetal sex on placental androgen signalling in a non-human primate model of pregnancy.

Brain oscillations are critical for neural communication and are increasingly recognized as sensitive biomarkers of neuropsychiatric dysfunction. Specifically, the auditory steady-state response (ASSR) has been identified as a reliable assessment of cortical entrainment and is a potential biomarker for the diagnosis or even prognosis of schizophrenia. Despite the growing awareness of sex as a biological variable, sex differences in oscillatory dynamics remain underexplored.

The brain-gut system, which involves bidirectional communication between the central nervous system and the gut, plays a central role in stress responses. Its dysregulation is implicated in irritable bowel syndrome (IBS), a stress-sensitive, female-predominant disorder characterized by abdominal pain and altered bowel habits. Adverse childhood experiences (ACE) increase the risk and severity of IBS, likely by amplifying stress responsiveness and gut-brain dysfunction in females. However, the mechanisms involved are unknown.

Sex differences are crucial to understanding neuropsychiatric disorders, yet they are often overlooked in the development of therapies. Transcranial alternating current stimulation (tACS) shows promise for cognitive enhancement, but its sex-specific effects are largely unknown.

Amyloid β oligomers (oAβ) are a key pathogenic driver in Alzheimer's Disease (AD). Neuronal G protein-gated inwardly rectifying K (GIRK/Kir3) channels are important regulators of neuronal excitability and prominent somatodendritic effectors for inhibitory G protein-coupled receptors, including the γ-aminobutyric acid type B receptor (GABAR). We previously reported a male-specific suppression of GIRK channel activity in hippocampal (HPC) neurons evoked by oAβ in in vitro, ex vivo, and in vivo mouse models of AD, and showed that this adaptation correlated with synaptic and cognitive impairment. Using pharmacological approaches, we showed that this adaptation is mediated by co-activation of cellular prion protein (PrP) and metabotropic glutamate receptor 5 (mGluR5) and requires activation of cytosolic phospholipase A2 α (cPLAα). However, the mechanisms underlying the sex specificity was unknown. Given the clinical context that females exhibit a 2-fold higher incidence of AD than males, and the loss of neuroprotective estrogen by menopause contributes to the sex differences in AD, we postulated that estrogen-associated resilience underlies this sex dimorphism of oAβ action.

Many systematic reviews have summarized evidence on the association between behavioural factors and incident cancers. To date, there has been little synthesis of heterogeneity by sex/gender of this evidence.An umbrella review was conducted of systematic reviews with quantitative synthesis (meta-analysis, meta-regression) examining the exposures of body size; physical activity; wholegrains, vegetables, fruit and beans; "fast foods"; red and processed meat; sugar sweetened drinks; dietary supplements; alcohol; tobacco; and sun exposure with incident non-sex-specific cancers. A search of Ovid MEDLINE, Ovid Embase, and Cochrane library from database inception to May 2023 was conducted. We calculated the proportion of systematic reviews that provided quantitative sex/gender findings (e.g., subgroup analyses) and summarized findings narratively. Methodological quality was appraised with the AMSTAR-2 tool.From 13,227 records, 705 full-text systematic reviews were identified as meeting inclusion criteria. Of these, 361 (51.2%) reported quantitative sex/gender findings. The terms "sex" and "gender" were used interchangeably by 36.3% of the 361 systematic reviews and none reported findings for transgender, gender-diverse, or non-binary individuals. Overall, 98.6% (356/361) of systematic reviews were rated "critically low" with the AMSTAR-2 tool. Most of the 361 systematic reviews with quantitative sex/gender findings reported no statistically significant differences by sex/gender.This umbrella review found conflation of sex and gender in systematic reviews of behavioural factors and non-sex-specific cancers and a lack of research among non-cisgender individuals. The existing evidence base is of critically low quality and our findings of no sex/gender-specific trends must be interpreted with caution.