Influence Sex Differences Research Articles

Socioeconomic factors and sex effects of postpartum maternal depression on offspring internalizing symptoms: a systematic review and meta-analysis

BackgroundPostpartum maternal depression and socioeconomic factors are established risk factors for the mental health of offspring. It has been consistently unclear as to whether female or male offspring are more vulnerable to the effects of postpartum maternal depression at different stages of the child’s life course. To determine whether the characteristics of postpartum maternal depression with a history of prenatal depression influence sex differences in offspring internalizing symptoms across childhood and adolescence, socioeconomic factors should be considered.MethodsWe systematically searched PubMed, Embase, PsycINFO, CNKI, and SinoMed databases from inception to November 28, 2023, and selected longitudinal cohort studies that quantified sex differences in internalizing symptoms of children and adolescents. Pooled standardized mean differences (SMDs) were calculated using random-effects models. ROBINS-E tool was used to rate the quality of evidence.ResultsTwenty-eight studies were eligible between 1997 and 2023, including 24,022 mother–child dyads. Sex-difference trajectories of offspring internalizing symptoms were identified after exposure to postpartum maternal depression, ranging from a lack of significant sex differences in childhood to a higher prevalence observed among girls than boys in adolescence (SMD, 0.25, 95% CI, 0.13–0.38). Economic income and maternal education affected the associations between the magnitude and concurrent recurrence of postpartum depression and significant sex differences in adolescent internalizing symptoms, respectively. After adjusting for socioeconomic factors, early nonconcurrent recurrence of postpartum depression was associated with greater odds of internalizing symptoms among adolescent girls than among boys (β = 0.03, 95% CI, 0.01–0.06); however, there was no statistical significance after adjusting for prenatal depression.ConclusionsSocioeconomic factors differentially impacted the association between postpartum maternal depression and significant sex differences in adolescent internalizing symptoms. Independent of socioeconomic factors and prenatal depression, postpartum maternal depression was not associated with significant sex differences in adolescent internalizing symptoms. Therefore, the significant sex effects of postpartum maternal depression are more likely due to complex interactions between maternal depression and the intrauterine and postpartum environments that shape offspring sex-difference trajectories, with consequences occurring for later internalizing symptoms in adolescence.Trial registrationPROSPERO, CRD42022301445.

Sex Differences in Spatiotemporal Consistency and Effective Connectivity of the Precuneus in Autism Spectrum Disorder.

Autism spectrum disorder (ASD) has been reported to exhibit altered local functional consistency. However, previous studies mainly focused on male samples and explored the temporal consistency in the ASD brain ignoring the spatial consistency. In this study, FOur-dimensional Consistency of local neural Activities (FOCA) analysis was used to investigate the sex differences of local spatiotemporal consistency of spontaneous brain activity in ASD. This study used resting-state functional magnetic resonance imaging data from the Autism Brain Imaging Data Exchange database, including 64 males/64 females with ASD and 64 male/64 female neurotypical controls (NCs). Two-way analysis of variance was performed to ascertain diagnosis-by-sex interaction effects on whole brain FOCA maps. Moreover, granger causal analysis was used to investigate effective connectivity between the brain regions with interaction effects and the whole-brain in ASD. Significant diagnosis-by-sex interaction effects on FOCA were observed in the bilateral precuneus (PCUN), bilateral medial prefrontal cortex and right dorsolateral superior frontal gyrus. Specifically, FOCA was significantly increased in males with ASD but decreased in females with ASD in the PCUN compared with the sex-matched NC group. In addition, the lack of sex differences in the causal influences from the bilateral anterior cingulate cortex/medial prefrontal cortex to the PCUN was observed in ASD. Our results reveal altered sex differences in the spatiotemporal consistency of spontaneous brain activity and functional interaction of the anterior and posterior default mode network (DMN) in ASD, highlighting the critical role of the DMN in the sex heterogeneity of ASD.

Sex differences in mitochondrial gene expression during viral myocarditis

BackgroundMyocarditis is an inflammation of the heart muscle most often caused by viral infections. Sex differences in the immune response during myocarditis have been well described but upstream mechanisms in the heart that might influence sex differences in disease are not completely understood.MethodsMale and female BALB/c wild type mice received an intraperitoneal injection of heart-passaged coxsackievirus B3 (CVB3) or vehicle control. Bulk-tissue RNA-sequencing was conducted to better understand sex differences in CVB3 myocarditis. We performed enrichment analysis and functional validation to understand sex differences in the transcriptional landscape of myocarditis and identify factors that might drive sex differences in myocarditis.ResultsAs expected, the hearts of male and female mice with myocarditis were significantly enriched for pathways related to an innate and adaptive immune response compared to uninfected controls. Unique to this study, we found that males were enriched for inflammatory pathways and gene changes that suggested worse mitochondrial electron transport function while females were enriched for pathways related to mitochondrial homeostasis. Mitochondria isolated from the heart of males were confirmed to have worse mitochondrial respiration than females during myocarditis. Unbiased TRANSFAC analysis identified estrogen-related receptor alpha (ERRα) as a transcription factor that may mediate sex differences in mitochondrial function during myocarditis. Transcript and protein levels of ERRα were confirmed as elevated in females with myocarditis compared to males. Differential binding analysis from chromatin immunoprecipitation (ChIP) sequencing confirmed that ERRα bound highly to select predicted respiratory chain genes in females more than males during myocarditis.ConclusionsFemales with viral myocarditis regulate mitochondrial homeostasis by upregulating master regulators of mitochondrial transcription including ERRα.

Androgens suppress the sialyltransferases ST3GAL1 and ST3GAL4 and modulate mucin 10 glycosylation in the submandibular gland, related to sex differences in commensal microbiota composition in mice.

Sex differences exist in the commensal microbiota that impact on multiple physiological processes in the host. Here, we examined the mechanism by which the sex differences are formed. In addition to the epithelial ductal cell, the acinar cell mass in the submandibular gland was associated with androgen-androgen receptor (AR) signaling. There was a sex difference in the formation of submandibular mucin 10 (MUC10) in SDS-PAGE. Neuraminidase treatment, which hydrolyzes terminal sialic acid, influenced the mobility shift of MUC10. Androgen-AR signaling negatively regulated St3 β-galactoside α-2,3-sialyltransferase 1 (St3gal1) and St3gal4 in the submandibular gland. There was a trend and significant sex differences in α-diversity (Shannon, p=0.09) and β-diversity (unweighted UniFrac) in oral microbiota composition, respectively. Some female-preferring bacteria including Akkermansia muciniphila can assimilate mucin by degrading terminal sialic acids. Our results indicate that androgen-AR signaling suppresses ST3GAL1 and ST3GAL4, which can influence sex differences in commensal microbiota composition.

Immune responses influence sex differences in Alzheimer disease.

Immune responses influence sex differences in Alzheimer disease.

Sex Differences in Alcohol Use: Is It All About Hormones?

Risky alcohol use and alcohol use disorders (AUD) are a rising problem in women, yet a major disparity in our understanding of what drives alcohol consumption in women remains. Historically biomedical research has focused on male subjects; however, recent increases in reporting of females, have highlighted major differences between the sexes. Here we review the current literature of the effect of gonadal steroid hormones (estrogens, androgens, and progestins), neurosteriods, and neurobiological factors on alcohol use in clinical and preclinical studies of both sexes. Further, we briefly discuss how fundamental sex differences in genetics, metabolism, neuroimmune, and stress responses may influence sex differences in alcohol intake. Comparing the sexes could aid in the discovery of novel therapeutics to treat AUD, and implementation of current treatment options in women.

Sex differences in the combined influence of inflammation and nutrition status on depressive symptoms: insights from NHANES.

Both nutrition and inflammation are associated with depression, but previous studies have focused on individual factors. Here, we assessed the association between composite indices of nutrition and inflammation and depression. Adult participants selected from the National Health and Nutrition Examination Survey (NHANES) between 2005 and 2018 were chosen. The exposure variable was the Advanced Lung Cancer Inflammation Index (ALI) integrating nutrition and inflammation, categorized into low, medium, and high groups. The outcome variable was depression assessed using the Patient Health Questionnaire-9 (PHQ-9). A multivariable logistic regression model was employed to evaluate the relationship between ALI and the risk of depression. After extensive adjustment for covariates, in the overall population, participants with moderate and high levels of ALI had a decreased prevalence of depression compared to those with low ALI levels, with reductions of 17% (OR, 0.83; 95% CI: 0.72-0.97) and 23% (OR, 0.77; 95% CI: 0.66-0.91), respectively. Among females, participants with moderate and high ALI levels had a decreased prevalence of depression by 27% (OR, 0.73; 95% CI: 0.60-0.88) and 21% (OR, 0.79; 95% CI: 0.64-0.98), respectively, compared to those with low ALI levels, whereas no significant association was observed among males. Subgroup analyses based on females and males yielded consistent results. In this study, we observed a negative correlation between moderate to high levels of ALI and the prevalence of depression, along with gender differences. Specifically, in females, greater attention should be given to the nutritional and inflammatory status.

Genetic and Environmental Influences on Perceived Stress in South Korean Twins.

Researchers have proposed that culture significantly influences perceived stress (PS). To date, however, twin studies on PS have been conducted mostly in western, individualistic cultures, which demonstrate that PS due to controllable (personal) life events is more heritable than PS due to uncontrollable (network) life events. This study aimed to investigate genetic and environmental influences on PS in South Korean twins. South Korea practices a dominant collectivist culture. In total, 1372 twin individuals (mean age = 22.4 ± 2.5 years) completed an online survey on PS, which consisted of the scales, Friendship, Academic Stress, Future Career, Family Conflicts, and Family Financial Difficulties (FFD). Friendship, Academic Stress, and Future Career can be considered PS due to personal life events, and Family Conflict and FFD, PS due to network life events. The general sex-limitation model-fitting analysis revealed the absence of qualitative or quantitative sex differences in genetic and environmental influences. Specifically, additive genetic influences were predominant for Friendship (63%), Academic Stress (67%), and Future Career (57%) for both sexes, with the remaining variance attributable to nonshared environmental influences. In contrast, shared environmental influences were largest for Family Conflict (47% for both genders) and FFD (64% for males, 63% for females) with no significant genetic effects. Despite known cultural differences in the means and variances of PS, South Korean twins exhibited significant genetic effects in PS due to personal life events and large shared environmental effects in PS due to network life events, which is similar to western samples.

Evolutionary trade-offs in dormancy phenology.

Seasonal animal dormancy is widely interpreted as a physiological response for surviving energetic challenges during the harshest times of the year (the physiological constraint hypothesis). However, there are other mutually non-exclusive hypotheses to explain the timing of animal dormancy, that is, entry into and emergence from hibernation (i.e. dormancy phenology). Survival advantages of dormancy that have been proposed are reduced risks of predation and competition (the 'life-history' hypothesis), but comparative tests across animal species are few. Using the phylogenetic comparative method applied to more than 20 hibernating mammalian species, we found support for both hypotheses as explanations for the phenology of dormancy. In accordance with the life-history hypotheses, sex differences in hibernation emergence and immergence were favored by the sex difference in reproductive effort. In addition, physiological constraint may influence the trade-off between survival and reproduction such that low temperatures and precipitation, as well as smaller body mass, influence sex differences in phenology. We also compiled initial evidence that ectotherm dormancy may be (1) less temperature dependent than previously thought and (2) associated with trade-offs consistent with the life-history hypothesis. Thus, dormancy during non-life-threatening periods that are unfavorable for reproduction may be more widespread than previously thought.

Evolutionary trade-offs in dormancy phenology

Seasonal animal dormancy is widely interpreted as a physiological response for surviving energetic challenges during the harshest times of the year (the physiological constraint hypothesis). However, there are other mutually non-exclusive hypotheses to explain the timing of animal dormancy, that is, entry into and emergence from hibernation (i.e. dormancy phenology). Survival advantages of dormancy that have been proposed are reduced risks of predation and competition (the ‘life-history’ hypothesis), but comparative tests across animal species are few. Using the phylogenetic comparative method applied to more than 20 hibernating mammalian species, we found support for both hypotheses as explanations for the phenology of dormancy. In accordance with the life-history hypotheses, sex differences in hibernation emergence and immergence were favored by the sex difference in reproductive effort. In addition, physiological constraint may influence the trade-off between survival and reproduction such that low temperatures and precipitation, as well as smaller body mass, influence sex differences in phenology. We also compiled initial evidence that ectotherm dormancy may be (1) less temperature dependent than previously thought and (2) associated with trade-offs consistent with the life-history hypothesis. Thus, dormancy during non-life-threatening periods that are unfavorable for reproduction may be more widespread than previously thought.

Sex differences in tech tilt and academic tilt in adolescence: Processing speed mediates age-tilt relations

Tilt refers to a pattern of specific abilities and is based on within subject differences in two abilities (e.g., technical and academic), producing relative strength in one ability (technical) and relative weakness in another ability (academic). This study examined sex differences in the development of tilt in adolescence (13- to 17-years) using the National Longitudinal Survey of Youth (N = 6969), a representative sample of adolescents in the United States. Tilt was based on within subject differences in technical (mechanical, electrical, automotive) and academic abilities (math or verbal) on the Armed Services Vocational Aptitude Battery. The differences produced tech tilt (technical > academic) and academic tilt (academic > technical). Consistent with investment theories and sex differences in technical preferences, males showed increases in tech tilt over time, whereas females showed increases in academic tilt over time, with sex differences in tilt increasing with age. In addition, processing speed and general intelligence (g) mediated most age-tilt relations, with age-tech tilt relations generally being stronger for males. The stronger age-tech tilt relations for males support investment theories and sex differences in vocational interests, which assume that stronger technical interests in males accelerate increases in tech tilt over time. The mediating effects of speed and g are consistent with cascade theories, which assume that age-related increases in speed boost g, which in turn boosts tilt. Future research should examine factors that influence sex differences in the development of tilt, including vocational interests (e.g., technical and academic), developmental period (e.g., later adulthood), and exceptional ability (e.g., intellectual giftedness).

Specific health beliefs mediate sex differences in food choice.

Although sex differences in dietary habits are well documented, the etiology of those differences is still a focus of research. The present study examines the role of specific health beliefs regarding healthy amounts of food for food choice and its relation to sex, more specifically, the assumption that sex differences in food choices are mediated by differentiating health beliefs. 212 German participants (44.3% female) aged 18-70 answered an online self-report questionnaire on their dietary habits and health beliefs, based on the recommendations of the German Nutrition Society. Most of the anticipated sex differences in food choice and some differences in health beliefs were found. The mediation hypothesis was partly supported, as the relationship between sex and fruit, vegetable, and fish consumption was mediated by the respective health beliefs. However, no mediation effects were found for meat, egg, cereal, and milk product consumption. The support for the mediation hypothesis aligns with previous findings and indicates that health beliefs might be an important pathway to fostering healthier food choices, especially for men. Nonetheless, sex differences in food choice were only partially mediated by sex differences in specific health beliefs, indicating that future studies might benefit from parallel mediation analyses to reveal the impact of other relevant factors influencing sex differences in food choice.

Sex differences in the efficacy of atrial fibrillation ablation according to the age: insights from a large-scale multicenter registry

Abstract Funding Acknowledgements Type of funding sources: None. Background We previously showed that females were associated with a higher risk of arrhythmia recurrence after radiofrequency catheter ablation (RFCA) of atrial fibrillation (AF). Whether age influences sex differences in terms of recurrence after CA of AF still remains unknown. Objective We sought to investigate the sex differences in the efficacy of RFCA of AF according to an advanced age. Methods We conducted a large-scale, prospective, multicenter, observational study (Kansai Plus Atrial Fibrillation Registry), enrolling 5010 consecutive patients who underwent an initial RFCA of AF at 26 centers (64±10 years; females, 27.3%; non-paroxysmal AF, 35.7%). The median follow-up duration was 2.9 years. Results The entire cohort was divided into either an age≥75 (n=790; females, 40.3%) and age < 75 years (n=4220; females, 24.9%). In the age≥75 group, the 3-year cumulative incidence of AF recurrences was identical between the sexes both after a single procedure (female vs. male, 38.1% vs. 40.7%, Log-rank P=0.39) and multiple procedures (22.3% vs. 21.6%, Log-rank P=0.96). On the other hand, in the age <75 group, females more frequently experienced AF recurrence than males both after a single procedure (female vs. male, 44.9% vs. 38.8%, Log-rank P=0.0003) and multiple procedures (24.7% vs. 19.3%, Log-rank P <0.0001). Conclusion While the incidence of an arrhythmia recurrence after radiofrequency catheter ablation of AF was similar between the sexes in patients with an age≥75, females had a higher incidence of recurrence than males in patients with an age <75.

Within versus between group designs, and not timing of onset of puberty, influence sex and age differences in intake of palatable food in rats

Understanding normative development of sensitivity to palatable food in adolescence is key to developing animal models for preclinical research of disorders of reward systems (e.g., eating disorders). Nevertheless, few studies have investigated changes in consumption of palatable food in both sexes and the role of the timing of onset of puberty as a factor. Here, we tested multiple ages of adolescence in both female and male Long-Evans rats and used both a within-group and between-group testing paradigm to compare effects of repeated testing on consumption of diluted sweetened condensed milk. In the within-group, female rats consumed more per body mass at postnatal day (P) 27 and declined in intake thereafter. Male rats also had the highest intake per body mass at P27 and declined thereafter, although a second peak was evident at P48, and the intake of females was greater than that of males from P41 on except at P48. In those tested at one age only (between-group design), there were no sex differences across ages, and the decline reached a plateau at P48 in both sexes. Further, intake per body weight was less in the between-group rats than in the within-group rats, suggesting that the within-group design used here as in previous studies may induce bingeing (excessive consumption in a discrete period of time). Thus, such a design may not capture normative development but rather sensitized intake akin to behavioural sensitization to drugs of abuse and/or binge-eating. There was no evidence of an effect of timing of puberty onset on intake in either design. The results show how methodological factors may compromise the interpretation of the development of, and sex differences in, the intake of palatable foods.

Changes in sex differences in neuroanatomical structure and cognitive behavior across the life span.

Sex differences occur in the structure and function of the rat cerebral cortex and hippocampus, which can change from the juvenile period through old age. Although the evidence is incomplete, it appears that in at least some portions of the cortex these differences develop due to the rise of ovarian hormones at puberty and are potentially not dependent on the perinatal rise in testosterone, which is essential for sexual differentiation of the hypothalamus and sexual behavior. During aging of female rats, the presence of continued ovarian hormone secretion after cessation of the estrous cycle also influences sex differences in neuroanatomical structure and cognitive behavior, resulting in nullification or reversal of sex differences seen in younger adults. Sex differences can be altered by experience in a stimulating environment during the juvenile/adolescent period, and sex differences in performance even can be affected by the parameters of a task. Thus, broad generalizations about differences such as "spatial ability" are to be avoided. It is clear that to understand how the brain produces behavior, sex and hormones have to be taken into account.

X chromosome agents of sexual differentiation.

Understanding sex differences in physiology and disease requires the identification of the molecular agents that cause phenotypic sex differences. Two groups of such agents are genes located on the sex chromosomes, and gonadal hormones. The former have coherent linkage to chromosomes that form differently in the two sexes under the influence of genomic forces that are not related to reproductive function, whereas the latter have a direct or indirect relationship to reproduction. Evidence published in the past 5 years supports the identification of several agents of sexual differentiation encoded by the X chromosome in mice, including Kdm5c, Kdm6a, Ogt and Xist. These X chromosome agents have wide pleiotropic effects, potentially influencing sex differences in many different tissues, a characteristic shared with the gonadal hormones. The identification of X chromosome agents of sexual differentiation will facilitate understanding of complex intersecting gene pathways underlying sex differences in disease.

Severity of alcohol use disorder influences sex differences in sleep, mood, and brain functional connectivity impairments.

Growing evidence suggests greater vulnerability of women than men to the adverse effects of alcohol on mood and sleep. However, the underlying neurobiological mechanisms are still poorly understood. Here, we examined sex difference in resting state functional connectivity in alcohol use disorder using a whole-brain data driven approach and tested for relationships with mood and self-reported sleep. To examine whether sex effects vary by severity of alcohol use disorder, we studied two cohorts: non-treatment seeking n = 141 participants with alcohol use disorder (low severity; 58 females) from the Human Connectome project and recently detoxified n = 102 treatment seeking participants with alcohol use disorder (high severity; 34 females) at the National Institute on Alcohol Abuse and Alcoholism. For both cohorts, participants with alcohol use disorder had greater sleep and mood problems than healthy control, whereas sex by alcohol use effect varied by severity. Non-treatment seeking females with alcohol use disorder showed significant greater impairments in sleep but not mood compared to non-treatment seeking males with alcohol use disorder, whereas treatment-seeking females with alcohol use disorder reported greater negative mood but not sleep than treatment-seeking males with alcohol use disorder. Greater sleep problems in non-treatment seeking females with alcohol use disorder were associated with lower cerebello-parahippocampal functional connectivity, while greater mood problems in treatment-seeking females with alcohol use disorder were associated with lower fronto-occipital functional connectivity during rest. The current study suggests that changes in resting state functional connectivity may account for sleep and mood impairments in females with alcohol use disorder. The effect of severity on sex differences might reflect neuroadaptive processes with progression of alcohol use disorder and needs to be tested with longitudinal data in the future.

Sex and Gender Differences in Environmental Influences on Dementia Incidence in Germany, 2014-2019: An Observational Cohort Study Based on Health Claims Data.

Background:There is an ongoing debate about whether environmental characteristics influence dementia risk like individual traits do, and whether these differ by sex and gender.Objective:This study examines the influence of regional characteristics on the incidence of dementia and explores sex and gender differences using individual-level health information and regional characteristics.Methods:Using a random sample of 250,000 people aged 70 + insured through Germany’s largest German public health agency, we analyzed quarterly data about diagnoses and place of residence from 2014 to 2019. Using five-digit postal codes, we added data on various dimensions of regional characteristics offered by the INKAR database and the 2011 Census database. We used multilevel survival regressions to tease out regional incidence differences while accounting for spatial clustering.Results:After adjusting for multi-morbidity and relocation-related selection bias, we saw that people living in regions with the highest tertile of income (HR = 0.87, p < 0.001), and who had the highest tertile of remaining life expectancy at age 60 (HR = 0.93, p = 0.012) had lower dementia risks. There was no gender difference in the regional income effect, but the effect of education (HR = 0.91, p = 0.015) was significant only for men and remaining life-expectancy was significant only for women (HR = 0.93, p = 0.026).Conclusion:Environmental characteristics related to wealth and health resources of a region influence the risk of dementia among the elderly in Germany. This effect is independent of the health profiles of the individuals and differs between the two genders. Health policies need to acknowledge these modifiable risk factors and consider how they affect men and women differently.

Male Cayo Santiago rhesus macaques (Macaca mulatta) tend to have greater molar wear than females at comparable ages: exploring two possible reasons why.

Objectives(1) To investigate sex differences in molar wear in known‐age Cayo Santiago rhesus macaques (Macaca mulatta) and, (2) To explore sex differences in body weight and molar eruption timing as factors influencing sex differences in molar wear.Materials and methodsData set I comprises wear scores, ages and body weights of 212 living monkeys included in the 1985 roundup. Data set II consists of molar wear measurements taken on 2D images of 103 of these monkeys' dental remains. Ordinal logistic regression was used to analyze the first data set. General linear models were used to analyze the second.ResultsMales generally exhibited more wear than females at equivalent chronological ages, though results varied by tooth type for the second data set. Male body weight in the full 1985 living sample was significantly related to dental wear, when age was taken into account; however, when males less than 8 years of age were eliminated from the sample, the association between dental wear and weight became statistically insignificant. Analysis of the second data set suggested no statistically significant sex difference in dental wear for third molars, despite the approximately 2 year sex difference in eruption age for this tooth type.DiscussionThis study suggests that body weight in males might be a predictor of dental wear and that if it is, body weight might also influence sex differences in dental wear. Sex differences in dental eruption timing do not appear to explain sex differences in dental wear in this sample.

The Curious Case of the Naked Mole-Rat: How Extreme Social and Reproductive Adaptations Might Influence Sex Differences in the Brain.

Research in the neurobiology of sex differences is inherently influenced by the study species that are used. Some traditional animal research models, such as rats and mice, show certain sex differences in the brain that have been foundational to neurobiological research. However, subsequent work has demonstrated that these differences are not always generalizable, especially to species with different social structures and sex-associated roles or behaviors. One such example is the naked mole-rat (Heterocephalus glaber), which has an unusual social structure among mammals. Naked mole-rats live in large groups where reproduction is restricted to a dominant female, called the "queen," and often only one breeding male. All other animals in the group, the "subordinates," are socially suppressed from reproduction and remain in a prepubescent state as adults, unless they are removed from the presence of the queen. These subordinates show little to no sex differences in external morphology, neural morphology, or behavior. However, there are a suite of neurobiological differences between subordinate and breeding naked mole-rats. After naked mole-rats attain breeding status, many of the classically sexually differentiated brain regions increase in volume (paraventricular nucleus, medial amygdala, bed nucleus of the stria terminalis). There are additionally social status differences in sex hormone receptor expression in the brain, as well as other changes in gene expression, some of which also show sex differences - though not always in the predicted direction based on other rodent studies. Data from naked mole-rats show that it is critical to consider the evolved social structure of a species when studying sex differences in the brain.