Biology of Sex Differences最新文献

Background: 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.

Methods: Using electrophysiological recordings in mice, this study investigated sex differences in both spontaneous and evoked oscillatory brain activity under baseline conditions and following systemic NMDA receptor suppression via ketamine, a widely used pharmacological model of schizophrenia.

Results: Although spontaneous oscillations across a wide range of frequency bands did not differ significantly between sexes, male mice exhibited greater gamma-band entrainment at 40 Hz ASSRs than females did. The administration of a subanaesthetic dose of ketamine consistently disrupted both spontaneous and gamma-band entrainment during ASSRs but without sex-specific effects. All measured oscillatory parameters showed high test‒retest reliability, thus indicating the robustness of the findings.

Conclusions: Collectively, these results demonstrate sex-dependent differences in baseline cortical entrainment, highlighting the importance of including both sexes in preclinical research to fully elucidate the neurobiological mechanisms underlying brain oscillations and their implications in psychiatric disorders.

Background: 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.

Methods: Pregnant baboons (Papio spp.) were randomly assigned to control diet (Ctrl; offspring female n = 5, male n = 6) or MNR diet (70% of global Ctrl; offspring female n = 5, male n = 5) at 0.16 gestation (term = ~ 180 days). Fetuses were delivered by Caesarean section at 0.9 gestation and placenta collected. Molecular measures of sex steroid signalling and placental function were quantified using established LC-MS/MS assays, Western blot, and qRT-PCR. Data were analysed using two-way ANOVA (factors: diet, sex) with Tukey's multiple comparison test.

Results: CYP17A1, SRD5A1, and PGF expression was higher, whereas HSD3B1, CYP19A1, and ANGPT2 was lower in male compared to female placentae, independent of diet. KDR expression and CYP19A1 activity increased in MNR versus Ctrl in females only. Cytoplasmic expression of the antagonistic AR variant, AR-45, was higher in males, whereas MNR increased cytoplasmic and nuclear AR-45 expression independent of sex.

Conclusions: Differences in placental steroidogenic and angiogenic genes, as well as androgen metabolism and signalling, may explain sex-specific placental responses to MNR. Better understanding of molecular regulators of androgen signalling may lead to novel, targetable therapeutics that improve placental function in complicated pregnancies associated with increased androgen concentrations.

Background: 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.

Methods: In this study, the effects of 10 Hz and 40 Hz tACS on spatial cognition were examined in male and female mice using three tests: the Y-maze to evaluate spatial recognition memory, the Barnes maze to evaluate spatial learning and memory related to punishment, and the reversal Barnes maze to evaluate reversal learning. General behaviors, such as anxiety, exploration, and locomotion, were evaluated using the elevated plus maze and open field tests.

Results: The results showed that 40 Hz tACS improved spatial recognition memory in males, while 10 Hz and 40 Hz tACS enhanced spatial learning in females. Males learned faster, while females performed better initially in the spatial learning process. In addition, no significant effects of tACS were observed in reversal learning, spatial memory, anxiety, or exploration. Interestingly, males exhibited reduced locomotion compared to females across tasks, and tACS potentially exacerbated this difference.

Conclusions: This animal study suggests that tACS may influence spatial cognition differently in males and females. Our findings highlight the importance of considering the interaction between sex and stimulation frequency when optimizing tACS intervention parameters.

The association between exposure to particulates in polluted air and cognitive impairment is an emerging and significant health concern, particularly among younger populations. Although exposure to particulate matter ≤ 2.5 μm (PM_2.5) is linked with a lower estimated risk for dementia compared to traditional risk factors such as APOEɛ4 gene variants, the widespread and long-term population exposure to PM_2.5 pose substantial implications for public health. This review explores the sex differences in cognitive function induced by PM_2.5, which are age-dependent and distinct from the sex bias observed in Alzheimer's disease. In addition to biological sex and sex hormones, we also discuss the role of epigenetic regulation as a mechanism underlying sex-specific cognitive vulnerabilities to environmental toxins, particularly PM_2.5. Understanding these differences is important for developing targeted interventions and public health strategies to mitigate the cognitive impacts of PM_2.5 exposure.

Background: To examine the impact of gender and its interaction with the side of surgery on cognition, affectivity, and quality of life (QOL) in drug-resistant epilepsy, as well as postsurgical changes in these domains.

Methods: In this prospective cohort study, 86 adults with TLE (46 women and 40 men) underwent a neuropsychological evaluation before and one year after surgery, including attention, executive function, language, verbal and visual memory, anxiety, depression, and QOL outcomes.

Results: After surgery, 84.1% of patients were seizure-free. In the group with right-sided surgery, men had poorer executive functioning (p = 0.05) and memory than women (for all, p < 0.05), independently of the time point (i.e., before or after surgery). Men with right-side surgery showed poorer executive function than those with left-side surgery (for all, p < 0.04), and a postsurgical anxiety decrease (p < 0.001). Women with right-side surgery had a better memory than those with left-side surgery, independently of the time point (for all, p < 0.001). Both genders showed postsurgical QOL improvements modulated by surgery side (p = 0.037). Regardless of the surgery side, women had poorer semantic fluency (p = 0.03) and QOL (p = 0.05) than men and postsurgical semantic fluency declines (p = 0.024), whereas men had postsurgical executive function declines (p = 0.05).

Conclusions: These findings underscore the importance of accounting for both gender and the side of surgery in understanding cognitive, affective, and QOL outcomes in patients with TLE, and could be useful for designing targeted neuropsychological interventions.

Background: Biological sex is a critical determinant in cardiovascular and renal disease outcomes. Although angiotensin II (Ang II) infusion is widely used to model hypertension in mice and rats, little is known about its effects in the Syrian hamster, a small rodent increasingly used for translational research. This study aimed to develop a model of chronic Ang II-induced hypertension in Syrian hamsters and investigate sex-specific differences in blood pressure, renal pathology, and components of the renin-angiotensin system (RAS).

Methods: Male and female Syrian hamsters (8-9 weeks old) were infused subcutaneously with Ang II (200 ng/kg/min) or saline via osmotic minipumps for four weeks. Mean arterial pressure (MAP) and kidney wet weight were determined on the euthanasia day. The kidneys were analyzed for renal pathology; renal RAS enzymes (ACE and ACE2) were measured by colorimetric assay and qPCR; cytokines (IL-6 and IL-1β) were measured by qPCR; and the angiotensin receptor type 1 (AT1R) was measured by radioligand binding and qPCR.

Results: Ang II infusion increased MAP in both sexes but elicited a significantly greater response in females (+ 50 mmHg) than males (+ 27 mmHg, p < 0.005). Female hamsters exhibited pronounced kidney injury, including acute tubular necrosis, glomerular sclerosis, and vascular fibrinoid necrosis, along with a 2-fold increase in kidney weight normalized to body weight. Ang II significantly downregulated renal ACE, ACE2, and AT₁R expression and activity in females but not in males. Renal IL-6 and IL-1β mRNA levels were elevated 20-fold and 3.9-fold, respectively, in females, compared to modest increases in males.

Conclusions: Female Syrian hamsters exhibit heightened vulnerability to Ang II-induced hypertension and renal damage compared to males, marked by exaggerated blood pressure elevation, enhanced renal inflammation, and suppression of classical RAS components. This novel hamster model provides a unique platform for studying sex-specific mechanisms of hypertension and renal pathology, with translational relevance for subpopulations of women who are at increased risk of Ang II-dependent hypertension-associated renal disease.

When used as variables in biomedical research, sex and gender can be difficult to operationalize and measure. Questions have arisen about whether either category is stable or causally meaningful in a research context. Here, we discuss some of the limitations of using both or even one of these categories in correlational or experimental work. We argue that attempting to draw a distinction between sex and gender can reignite the nature/nurture debate, inadvertently bringing outdated metaphors and assumptions about innateness and causation into our research. Many researchers, including ourselves, have described sex and gender as separate collections of causal factors (which we describe as a "bucket" metaphor) or as entangled (a "knot" metaphor). Because they regard sex and gender as conceptually separable and internally consistent, such metaphors have limited value for understanding the drivers of diversity in our data. Rather than continuing to reify sex and gender as distinct buckets or threads of explanatory variables, we call for deconstruction of these categories by focusing instead on clearly operationalized, instantiating variables that researchers can manipulate or measure. Our proposed approach differs from recent, similar calls in that we are not suggesting the exclusion of a sex/gender category from statistical models; instead, we recommend keeping it-not as a representation of biological reality, but as a tool used under a careful set of assumptions. We provide example datasets to illustrate how a sex/gender category can, when thoughtfully operationalized, be used to improve statistical rigor and inferential precision. In addition, we advocate for attention to variation within sex/gender, which is more informative in investigations of mechanism than comparing means across sex/gender categories.