Unexplored functions of sex hormones in glioblastoma cancer stem cells

Biological sex impacts a wide array of molecular and cellular functions that impact organismal development and can influence disease trajectory in a variety of pathophysiological states. In non-reproductive cancers, epidemiological sex differences have been observed in a series of tumors, and recent work has identified previously unappreciated sex differences in molecular genetics and immune response. However, the extent of these sex differences in terms of drivers of tumor growth and therapeutic response is less clear. In glioblastoma, the most common primary malignant brain tumor, there is a male bias in incidence and outcome, and key genetic and epigenetic differences, as well as differences in immune response driven by immune-suppressive myeloid populations, have recently been revealed. Glioblastoma is a prototypic tumor in which cellular heterogeneity is driven by populations of therapeutically resistant cancer stem cells (CSCs) that underlie tumor growth and recurrence. There is emerging evidence that GBM CSCs may show a sex difference, with male tumor cells showing enhanced self-renewal, but how sex differences impact CSC function is not clear. In this mini-review, we focus on how sex hormones may impact CSCs in GBM and implications for other cancers with a pronounced CSC population. We also explore opportunities to leverage new models to better understand the contribution of sex hormones versus sex chromosomes to CSC function. With the rising interest in sex differences in cancer, there is an immediate need to understand the extent to which sex differences impact tumor growth, including effects on CSC function.

Salt sensitivity of blood pressure and aldosterone: interaction between Lysine-specific demethylase 1 gene, sex, and age

Context Salt sensitivity of blood pressure (SSBP) is associated with increased cardiovascular risk, especially in individuals of African descent, although underlying mechanisms remain obscure. Lysine-specific demethylase 1 (LSD1) is a salt-sensitive epigenetic regulator associated with SSBP and aldosterone dysfunction. An LSD1 risk allele in humans is associated with SSBP and lower aldosterone levels in hypertensive African but not European descent. Heterozygous knockout LSD1 mice display SSBP and aldosterone dysregulation, but this effect is modified by age and biological sex. This might explain differences in cardiovascular risk with aging and biological sex in humans. Objective To determine if LSD1 risk allele (rs587618) carriers of African descent display a sex-by-age interaction with SSBP and aldosterone regulation. Methods We analyzed 297 individuals of African and European descent from the HyperPATH cohort. We performed multiple regression analyses for outcome variables related to SSBP and aldosterone. Results LSD1 risk allele carriers of African (but not European) descent had greater SSBP than non-risk homozygotes. Female LSD1 risk allele carriers of African descent had greater SSBP, mainly relationship-driven by women of low estrogen (postmenopausal). There was a significant LSD1 genotype-sex interaction in aldosterone response to angiotensin II stimulation in individuals ≤50 years, with female carriers displaying decreased aldosterone responsiveness. Conclusions SSBP associated with LSD1 risk allele status is driven by women of deplete estrogen state. Mechanisms related to a resistance to develop SSBP in females are uncertain but may relate to an estrogen modulating effect on mineralocorticoid receptor activation and/or LSD1 epigenetic regulation of the mineralocorticoid receptor.

Role of Biological Sex in the Cardiovascular-Gut Microbiome Axis

There has been a recent, unprecedented interest in the role of gut microbiota in host health and disease. Technological advances have dramatically expanded our knowledge of the gut microbiome. Increasing evidence has indicated a strong link between gut microbiota and the development of cardiovascular diseases (CVD). In the present article, we discuss the contribution of gut microbiota in the development and progression of CVD. We further discuss how the gut microbiome may differ between the sexes and how it may be influenced by sex hormones. We put forward that regulation of microbial composition and function by sex might lead to sex-biased disease susceptibility, thereby offering a mechanistic insight into sex differences in CVD. A better understanding of this could identify novel targets, ultimately contributing to the development of innovative preventive, diagnostic and therapeutic strategies for men and women.

Trade-Offs Between Hepatic Host Defense and Metabolic Programs Underlie Sex-Biased Diseases

Current concepts in evolutionary medicine propose that trade-offs and mismatches with a shifting environment increase disease risk. While biological sex also impacts disease prevalence, contributions of environmental pressures to sex-biased diseases remain unexplored. Here, we show that sex-dependent hepatic programs confer a robust (~300%) survival advantage for male mice during lethal bacterial infection. The transcription factor BCL6, which masculinizes hepatic gene expression at puberty, is essential for this advantage. However, protection by BCL6 comes at a cost following dietary excess, resulting in overt fatty liver and glucose intolerance in males. Deleting hepatic BCL6 reverses these phenotypes but markedly lowers male fitness during infection, thus establishing a sex-dependent tradeoff between host defense and metabolic systems. We suggest that these tradeoffs, coupled with current environmental pressures, drive metabolic disease in males.

Girls’ Stuff? Maternal Gender Stereotypes and Their Daughters’ Fear

One of the most robust findings in psychopathology is the fact that specific phobias are more prevalent in women than in men. Although there are several theoretical accounts for biological and social contributions to this gender difference, empirical data are surprisingly limited. Interestingly, there is evidence that individuals with stereotypical feminine characteristics are more fearful than those with stereotypical masculine characteristics; this is beyond biological sex. Because gender role stereotypes are reinforced by parental behavior, we aimed to examine the relationship of maternal gender stereotypes and children’s fear. Dyads of 38 mothers and their daughters (between ages 6 and 10) were included. We assessed maternal implicit and explicit gender stereotypes as well as their daughters’ self-reported general fearfulness, specific fear of snakes, and approach behavior toward a living snake. First, mothers’ fear of snakes significantly correlated with their daughters’ fear of snakes. Second, mothers’ gender stereotypes significantly correlated with their daughters’ self-reported fear. Specifically, maternal implicit gender stereotypes were associated with daughters’ fear of snakes and fear ratings in response to the snake. Moreover, in children, self-reported fear correlated with avoidance of the fear-relevant animal. Together, these results provide first evidence for a potential role of parental gender stereotypes in the development and maintenance of fear in their offspring.

Factors associated with the perception of fear of COVID-19 in university students

ABSTRACT Objective: to analyze the factors associated with the perception of fear of COVID-19 in Brazilian university students. Methods: this is an online, cross-sectional analytical study conducted at a Brazilian public university with 1,437 undergraduate students between September and November 2020. The Fear of COVID-19 Scale was used to measure the main construct. Data analysis was performed using Mann-Whitney U test, Cohen’s r test and multiple linear regression analysis. Results: factors associated with fear of COVID-19 in university students were the variables biological sex, perception of good sleep quality, many days of access to information, not complying with social distancing, reporting sufficient hours of sleep, not having a partner, guidance sexual non-heterosexual, being in the risk group for COVID-19 and tobacco consumption. Conclusions: the study findings can contribute to the discussion about the weaknesses that the university population is experiencing in this pandemic period.

Near-Infrared Spectroscopy (NIRS) as a Method for Biological Sex Discrimination in the Endangered Houston Toad (Anaxyrus houstonensis)

Biological sex is one of the more critically important physiological parameters needed for managing threatened animal species because it is crucial for informing several of the management decisions surrounding conservation breeding programs. Near-infrared spectroscopy (NIRS) is a non-invasive technology that has been recently applied in the field of wildlife science to evaluate various aspects of animal physiology and may have potential as an in vivo technique for determining biological sex in live amphibian species. This study investigated whether NIRS could be used as a rapid and non-invasive method for discriminating biological sex in the endangered Houston toad (Anaxyrus houstonensis). NIR spectra (N = 396) were collected from live A. houstonensis individuals (N = 132), and distinct spectral patterns between males and females were identified using chemometrics. Linear discriminant analysis (PCA-LDA) classified the spectra from each biological sex with accuracy ≥ 98% in the calibration and internal validation datasets and 94% in the external validation process. Through the use of NIRS, we have determined that unique spectral signatures can be holistically captured in the skin of male and female anurans, bringing to light the possibility of further application of this technique for juveniles and sexually monomorphic species, whose sex designation is important for breeding-related decisions.