Biology of Sex Differences最新文献

{"title":"Timing matters: a prospective investigation of father absence and pubertal timing in girls and boys.","authors":"Taylor M Drazan, Natasha Chaku","doi":"10.1186/s13293-026-00868-y","DOIUrl":"10.1186/s13293-026-00868-y","url":null,"abstract":"<p><strong>Background: </strong>Puberty is beginning earlier across cultures and geographic regions. Father absence is one of the most robust psychosocial predictors of earlier pubertal timing. Yet the importance of its timing (i.e., when absence and presence are most impactful), variability (i.e., fluctuations in absence and presence), and consistency (i.e., the persistence of absence or presence) remains understudied, as do the developmental mechanisms that underlie associations between father absence and pubertal timing.</p><p><strong>Methods: </strong>Data were obtained from the Future of Families and Child Wellbeing Study, a prospective cohort of 4,898 participants. Father absence was indexed via mother-reports at birth, and ages 1, 3, 5, and 9. Pubertal timing was indexed via breast development in girls, facial hair growth in boys, and pubic and underarm hair in both at age 9. Relative maturation was also assessed at ages 9 and 15. Child body mass index, father depression, and material hardship were examined as possible mediators at age 5.</p><p><strong>Results: </strong>Four distinct patterns of father absence emerged, representing fathers who were (1) consistently absent, (2) absent early in life but present later in childhood, (3) present early in life but absent later in childhood, and (4) consistently present. Consistent father absence and father absence in the first year of life only were associated with earlier breast development in girls and earlier facial hair growth in boys, but not earlier pubic and underarm hair growth; father absence was inconsistently associated with indicators of relative maturation. None of the proposed mediators significantly mediated these associations.</p><p><strong>Conclusions: </strong>The findings from this prospective cohort study suggest that father absence, particularly in the first year of life, is associated with signs of earlier pubertal timing in both girls and boys. These patterns are consistent with sensitive period hypotheses, but must be further investigated in the context of broader signals of adversity and resilience.</p>","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13122871/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147484676","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuroglial CB1 receptors modulate hippocampal processes in a sex-dependent manner.","authors":"Jon Egaña-Huguet, Lucía Sangroniz-Beltrán, Andrés M Baraibar, Pablo Reyes-Velásquez, Nicolas F Landgraf, Paula Torres-Maldonado, Cathaysa Rodríguez-Cedrés, Francisca Julio-Kalajzic, Joaquín Piriz, Almudena Ramos, Pedro Grandes, Giovanni Marsicano, Susana Mato, María Ceprián, Edgar Soria-Gómez","doi":"10.1186/s13293-026-00886-w","DOIUrl":"10.1186/s13293-026-00886-w","url":null,"abstract":"<p><strong>Background: </strong>Navigation and memory are hippocampal functions that are essential for survival. One of the key modulators of hippocampal activity is the endocannabinoid system through the cannabinoid receptor type 1 (CB1). CB1 is widely expressed in various types of hippocampal cells. While it is known that CB1 participates in memory processes, its specific roles in different cell types and differences between sexes remain unclear.</p><p><strong>Methods: </strong>This study investigates the cell- and sex-specific modulation of navigation and memory by CB1 receptors. To this end, we selectively deleted CB1 receptors from hippocampal neurons or astrocytes in adult male and female mice. We then assessed its effect on a comprehensive range of behaviors, including innate emotional responses, memory, navigation, and nesting.</p><p><strong>Results: </strong>Deletion of CB1 from hippocampal principal cells or astrocytes produced significant changes in innate emotional behavior and novel object recognition in both sexes. Conversely, CB1 receptor deletion from all neurons produced deficits in spatial navigation exclusively in males. Interestingly, synaptic plasticity was impaired in both male and female mice lacking CB1 receptors from GFAP-positive cells. Nest-building behavior was only affected in males carrying the CB1 deletion in CAMK-positive cells.</p><p><strong>Conclusion: </strong>In conclusion, our findings show that neuronal CB1 receptors are critical for spatial navigation in males, while astrocytic CB1 receptors play a key role in memory processes in both males and females.</p>","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13162385/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147484610","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association between parental age at childbirth and timing of puberty in children: an 8-year cohort study.","authors":"Qin Zhang, Chengpeng Cui, Zeqin Peng, Siyan Ye, Yan Li, Di Wu, Qin Liu","doi":"10.1186/s13293-026-00877-x","DOIUrl":"10.1186/s13293-026-00877-x","url":null,"abstract":"&lt;p&gt;&lt;p&gt;BACKGROUND: The timing of puberty in offspring is influenced by various factors, including genetics and environment. While some studies suggest a link between parental age at childbirth and pubertal timing, the evidence remains inconsistent. This study aimed to investigate the association between parental age at reproduction and the timing of pubertal development events in their sons and daughters. METHODS: We conducted a prospective cohort study with 1,386 children (51.7% girls) followed for a median of 7.00 years. Parental age was collected retrospectively. Pubertal development, including genital, breast, and pubic hair growth, as well as spermarche and menarche, was assessed semiannually. Accelerated Failure Time-Restrictive Cubic Spline models were used to analyze the impact of paternal and maternal age on the timing of these pubertal events. RESULTS: Advanced maternal age at childbirth was significantly associated with an earlier age at spermarche in boys (P &lt; 0.05). A non-linear association was also observed between maternal age at childbirth and the timing of genital development (P = 0.01). Both maternal and paternal ages at childbirth were significantly associated with the timing of breast and axillary hair development onset in girls in a non-linear, inverse U-shaped manner (P = 0.02 and P &lt; 0.01, respectively), indicating that both younger and older parental ages are linked to the earlier breast and axillary hair development. CONCLUSIONS: This study suggests that parental age at childbirth is associated with pubertal development in offspring, including the timing of spermarche and genital development in boys and the onset of breast and axillary hair development in girls. Specifically, both younger and older parental ages have been linked to earlier attainment of these pubertal milestones, particularly among girls. In summary, the study showed that the specific pubertal events affected by parental age and the nature of that association were different for boys and girls. The timing of puberty can affect a child’s future health. The aim of this study was to investigate whether a parent’s age at the time of childbirth influences when their child enters puberty. We conducted a long-term (with a median duration of 7 years) follow-up study on 1386 children to track their pubertal development. We found that the effects of parental age differ between boys and girls. For boys, having an older mother at birth was linked to reaching spermarche (first ejaculation) at a younger age. For girls, the findings were more complex. Both younger and older parental ages were linked to earlier breast and underarm hair development. This U-shaped pattern means that girls born to very young or very old parents tended to show these signs of puberty sooner than those born to parents in the middle-age range. In short, this study suggests that a parent’s age does play a role in the timing of their child’s puberty, but the effects are different for boys and girls","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13112619/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147479652","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex-influenced DNA methylation differs by placental cell type.","authors":"Jiyoung Han, Amy M Inkster, Victor Yuan, Maria S Peñaherrera, Wendy P Robinson","doi":"10.1186/s13293-026-00869-x","DOIUrl":"10.1186/s13293-026-00869-x","url":null,"abstract":"<p><strong>Background: </strong>Sex differences in the function and morphology of the human placenta can lead to sex differences in pregnancy outcomes. X chromosome inactivation (XCI) is the primary mechanism for dosage compensation between the sexes, and is strongly associated with X-chromosome promoter DNA methylation (DNAme) in somatic cells. However, in the placenta, low X-chromosome promoter DNAme has been reported. The placenta is a complex organ consisting of cells of different developmental origins, but the sex differences in DNAme by specific cell types have not been investigated.</p><p><strong>Methods: </strong>We examined sex-influenced DNAme from 18 to 19 samples each of endothelial, stromal, cytotrophoblast and Hofbauer cells, sorted from term placentas, as well as matched whole chorionic villi. We also compared these profiles with data from 65 endothelial cell samples from placental chorionic plate arteries and veins (XX = 16, XY = 13) and umbilical cord veins (XX = 22, XY = 14). All data were derived from Illumina Infinium HumanMethylation450 or EPIC DNAme arrays. Sex-stratified analyses of the X/Y and autosomal DNAme were undertaken to identify DNAme differences associated with sex chromosome complement.</p><p><strong>Results: </strong>The DNAme distribution on both the X and Y chromosomes differed by cell type. These differences clustered according to the differing developmental origins from extraembryonic mesoderm (endothelial/stromal), trophectoderm (cytotrophoblast) and epiblast (Hofbauer cells), with Hofbauer cells sharing a similar distribution with blood and umbilical endothelial cells. Interestingly, the typical XCI-associated DNAme at promoter CpG islands (CGI) on the X-chromosome of XX cells was absent for endothelial/stromal cells and present only at low levels in trophoblasts, suggesting that de novo establishment of promoter-CGI DNAme on the X-chromosome may differ by cell type.</p><p><strong>Conclusion: </strong>The lack of X-linked promoter DNAme in extraembryonic mesoderm-derived cells (endothelial/stromal) is consistent with a distinct developmental origin of these populations relative to the other placental and umbilical cell types. Autosomal DNAme also showed cell-type differences in alignment with cellular relationships observed for sex chromosomes. This work suggests the effects of sex chromosome complement on pregnancy outcomes may differ by placental cell type.</p>","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13147677/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147479668","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex and gender effects on incidence of migraine and stroke: a longitudinal observational study based on the german socio-economic panel.","authors":"Mascha Kern, Hans-Aloys Wischmann, Alex Müller, Tobias Kurth, Stefanie Theuring","doi":"10.1186/s13293-026-00875-z","DOIUrl":"10.1186/s13293-026-00875-z","url":null,"abstract":"<p><strong>Background: </strong>Sex and gender both affect health outcomes, often in complex ways that intertwine biological and social influences. While researchers have criticized the conflation of sex and gender in quantitative studies, it remains a challenge to analytically disentangle them. We investigated an approach to conceptualize sex and gender as interrelated constructs embedded within a specific social context and estimate their direct effects on health outcomes simultaneously.</p><p><strong>Methods: </strong>To analyze migraine and stroke incidence from 2011 until 2022, we used longitudinal data from the representative German Socio-Economic Panel (SOEP) within a causal framework. We applied a directed acyclic graph (DAG) to formalize hypothesized effects of sex and gender. Gender was modeled as an unobserved latent variable, influenced by sex assigned at birth and indicated by a set of gender-related variables. We codified the causal model as a structural equation model (SEM), enabling the joint estimation of the latent gender construct and the direct effects of both sex and gender on the health outcomes. We tested prior hypotheses in the SEM and explored additional relationships using causal discovery techniques.</p><p><strong>Results: </strong>Migraine incidence was 3.1 times higher among participants of female sex (6.2% vs. 2.0%). Sex had the strongest effect on reporting a new migraine diagnosis (β = 0.044, 95% CI [0.033, 0.056], p < .001), while gender showed no direct effect. Stroke incidence was lower among female respondents (1.2% vs. 1.7%), with sex showing a statistically significant negative effect, indicating that slightly fewer female persons reported a new stroke diagnosis (β = -0.010, 95% CI [-0.017, -0.004], p < .01). In contrast, gender showed a small, but significant positive effect (β = 0.006, 95% CI [0.002, 0.009], p < .01), suggesting that gender-related characteristics that were more frequently reported by female individuals had an effect on stroke incidence.</p><p><strong>Conclusions: </strong>Both sex and gender differentially affected stroke, whereas only sex showed a direct effect on migraine. We demonstrated that biological and social dimensions of sex and gender can be systematically addressed within the same model including gender as an unobserved latent variable, while remaining attentive to contextual complexity.</p>","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13064216/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147466535","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Social defeat stress responses in the stress alternative model are dependent on sex and anterior basolateral amygdala orexin 2 receptors.","authors":"Jazmine D W Yaeger, Megan M John, Leighton J Ledesma, Trent L Greschke, J J Gale, Lauren S Meyer, Renée A Brummels, Wayne J Korzan, R Parrish Waters, Cliff H Summers","doi":"10.1186/s13293-026-00858-0","DOIUrl":"10.1186/s13293-026-00858-0","url":null,"abstract":"<p><strong>Background: </strong>Comprehending sex differences in stress vulnerability and the associated neurocircuitry has been elusive until the development of a method for investigating social defeat in female mice.</p><p><strong>Methods: </strong>The Stress Alternatives Model (SAM) uses conditioning-induced agonistic behavior from novel male aggressors to separate distinct phenotypes characterized by stress-resilient active avoidance (Escape) or vulnerability (no Escape = Stay).</p><p><strong>Results: </strong>Unlike males, females predominantly display Escape behavior, which is reversible (to Stay) by adding more social stress to behavioral environments. Despite this, females exhibit both stress-resilient and vulnerable phenotypic segregation. Stress-vulnerable females exhibit double conditioning-induced corticosterone secretion, more contextual fear conditioning, and reduced social preference. Systemic and intra-BLA injections of Orx₂R or α₂ antagonists resulted in slower escape (Escape^S), increased social avoidance, as well as increased cued and contextual freezing in stress-vulnerable females. Neurons in BLA express Orx₂R mRNA (Hcrtr2) predominantly in cholecystokinin-positive GABA neurons. In slower escape (Escape^S) females expression of Hcrtr2 and Adra2a in BLA is elevated.</p><p><strong>Conclusions: </strong>Female and male mice exposed to social stress exhibit distinct behavioral adaptations, but similarly, separate into resilient and susceptible subpopulations. Inhibiting Orx₂R promotes stress-vulnerable behavior in females, and modifies transcription in BLA microcircuits, suggesting a role for Orx₂R defining stress behavior.</p>","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13104226/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147462558","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The cognitive connectome of men and women: a study on sex differences across three cohorts.","authors":"Daphne Gasparre, Annegret Habich, Lídia Mulet-Pons, Roraima Yanez-Perez, Eric Westman, José Barroso, Lídia Vaque-Alcázar, David Bartres-Faz, Paolo Taurisano, Daniel Ferreira","doi":"10.1186/s13293-026-00866-0","DOIUrl":"10.1186/s13293-026-00866-0","url":null,"abstract":"<p><p>BACKGROUND: Cognitive processes are essential for efficient daily functioning. Demographic factors such as age and education influence cognitive performance. However, the impact of sex on cognition is less understood and previous research has reported inconsistent findings. We investigated sex differences in cognitively unimpaired adults in three cohorts, using two complimentary approaches: a univariate approach to compare direct performance across cognitive domains and the multivariate approach of graph theory to compare global and nodal features as well as the modular organization of cognitive connectomes. METHODS: We included 4,259 cognitively unimpaired participants (334 from the GENIC cohort, 3,703 from the National Alzheimer’s Coordinating Center [NACC], and 222 from the Alzheimer’s Disease Neuroimaging Initiative [ADNI]). Cognitive variables were corrected for age and education, and cognitive connectomes were constructed using Spearman correlation coefficients. Sex differences in cognitive performance were examined through ANCOVAs as well as global and nodal network measures. RESULTS: Univariate analyses showed significant sex differences in three out of five cognitive domains across cohorts, mainly of small effect sizes. Graph theory analyses revealed minimal sex differences in cognitive module organization and no significant differences on global network measures, except for a higher modularity observed in women compared to men in the NACC. In contrast, nodal analyses revealed sex differences in several network measures. CONCLUSIONS: Sex differences in cognition seem to be of small effect size and limited to specific cognitive domains or cognitive variables, while the overall organization and global features of cognitive connectomes were largely comparable between men and women. Future studies should clarify whether men and women may rely on slightly different cognitive strategies to approach cognitive tasks without overt differences in cognitive ability. </p>","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13063598/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147455478","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Divergent impacts of estradiol/testosterone reduction on biological aging: optimal HRT window in females recommended.","authors":"Yicheng Ma, Junming Han, Qihang Li, Xiao Jiang, Yuan Li, Keke Zhang, Ling Gao","doi":"10.1186/s13293-026-00873-1","DOIUrl":"10.1186/s13293-026-00873-1","url":null,"abstract":"<p><strong>Background: </strong>The age-specific magnitude of the impact of hormones on aging and the role of hormone replacement therapy (HRT) remain unclear.</p><p><strong>Methods: </strong>We used data from UK Biobank participants for our analysis. Linear and logistic regression models were employed to investigate the associations and its differences between estradiol/testosterone and biological age acceleration (BAA) across different age group. Then, females were divided into HRT and non-HRT groups, and restricted cubic splines were used to evaluate HRT initiation age and duration.</p><p><strong>Results: </strong>A total of 54,912 participants (71.99% females, 28.01% males) were enrolled, with 39,303 females assessed for the impact of HRT on aging. Estradiol decline in females was linked to a 0.18-0.29-year BAA increase, while testosterone decline in males was linked to a 0.07-0.71-year BAA increase. It showed estradiol protected against aging in females (most prominent at 41-55 years) while elevated testosterone accelerated aging. In males, testosterone was protective (most significant at 56-70 years) and estradiol had no notable effect. Quartile and age-stratified analyses confirmed these findings. In contrast, the decrease of estradiol was associated with biological age younger. Hormone replacement therapy (HRT) in females resulted in sustained BAA reduction (-4.5 to -6.0, 41-70 years) superior to non-HRT (-4.0 to -5.5). HRT initiated at 56-60 years showed optimal efficacy, with longer duration associated with more pronounced aging deceleration.</p><p><strong>Conclusions: </strong>The impact of per standard deviation (SD) decrease in sex hormone levels on aging (BAA) varies by age, with significant effects observed in females aged 50-55 years and males aged 65-70 years. These findings may facilitate the optimization of HRT timing to maximize anti-aging benefits and enable personalized treatment strategies.</p>","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13097923/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147442396","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prolonged social isolation promotes depressive-like behavior in male and female mice, with sex-related differences in the stress response.","authors":"Yamila Cepeda, Catalina Tobar, Naoko Jara, Claudio Carril-Pardo, Andrés Villarroel, Raúl Lagos, Antonia Recabal, Estefanía Nova-Lamperti, Ana María Obregón-Rivas, Pía M Vidal, Roberto Elizondo-Vega, Karina Oyarce","doi":"10.1186/s13293-026-00874-0","DOIUrl":"10.1186/s13293-026-00874-0","url":null,"abstract":"<p><strong>Background: </strong>Social isolation is a chronic psychological stressor with high translational relevance to depression in humans, particularly in the aftermath of the COVID-19 pandemic. However, few preclinical studies have evaluated its sex-dependent effects. Some studies have shown that after four weeks of social isolation, only males exhibit depressive-like behavior, without a comprehensive view of the underlying immune and neuroimmune alterations.</p><p><strong>Methods: </strong>Here, we examined the impact of prolonged social isolation on depressive- and anxiety-like behaviors of adult male and female mice, using the forced swim, splash, open field, and light/dark box tests. We also analyzed peripheral immune profiles through flow cytometry, ELISA and qRT-PCR, and neuroimmune responses through qRT-PCR and immunofluorescence for astrocytes and microglia.</p><p><strong>Results: </strong>After seven weeks of social isolation, both males and females exhibited depressive-like behavior and inflammatory signs such as elevated neutrophils in circulation, decreased IL-10 expression in the spleen, higher expression of IDO in the hippocampus, and higher microglia number. However, sex-related differences were also detected. Isolated males show lower body weight, with no changes in corticosterone levels, while isolated females exhibit increased corticosterone levels, higher IL-1β expression in the hippocampus, and higher microglia total area.</p><p><strong>Conclusions: </strong>After seven weeks of social isolation, both sexes exhibit depressive-like behavior, with sex-related differences in body weight, corticosterone levels, and cellular and molecular signs of neuroinflammation. These findings highlight the importance of temporality and sex as key variables in the behavioral and physiological responses to chronic stress. Given the increased prevalence of depression in women, these results provide new insights into sex-specific susceptibility to chronic stress and may inform the development of tailored diagnostic and therapeutic strategies.</p>","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13130425/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147442448","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluating sex and gender as separate and interactive predictors of memory aging trajectory classes: an integrative data-driven approach.","authors":"Linzy Bohn, Paige Vandenberg, Harrison Fah, M Natasha Rajah, Gillian Einstein, Roger A Dixon","doi":"10.1186/s13293-026-00864-2","DOIUrl":"10.1186/s13293-026-00864-2","url":null,"abstract":"<p><strong>Background: </strong>A priority in aging and dementia research is to integrate sex (biological attribute) and gender (sociocultural/behavioural characteristics) in theories, designs, analyses, and intervention protocols. We recently reported a data-mining procedure for operationalizing empirically-derived composite gender variables in archival databases. The present study extends the prior cross-sectional approach by examining sex and gender as separate and interactive predictors of longitudinal data-driven memory trajectory classes.</p><p><strong>Methods: </strong>Participants (N = 746) contributed baseline data for binary sex (female/male), education (years), and empirically-derived composite variables representing complementary gender facets. These facets included Manual Tasks and Physical Activities; Social and Household Management; Leisure, Socializing, and Travel; Cognitive Activity and Brain Games; Health Perceptions and Practices; and Subjective Memory Beliefs. We integrated these into a longitudinal episodic memory trajectory distribution spanning 42 years (53-95) of aging. Data-driven latent class growth analysis (LCGA) on the trajectory distribution identified discriminable classes. Using the R3STEP approach, we separately tested sex, gender facets, and education as predictors of membership in the higher (healthier) trajectory classes relative to the lowest (benchmark) class. We then included interaction terms to test for sex moderation of gender effects. Finally, we identified all genotyped participants and tested whether sex and gender effects were moderated by Apolipoprotein E (APOE).</p><p><strong>Results: </strong>LCGA revealed three memory classes: High-Stable (highest level/relatively stable), Moderate/Normal-Declining (average level/moderate decline), and Low-Declining (lowest level/steepest decline). Several variables separately predicted High-Stable membership. For sex, females were more likely than males to belong to this class. For gender, (a) higher scores for Social and Household Management, Cognitive Activity and Brain Games, and Subjective Memory Beliefs predicted High-Stable membership; and (b) higher scores for Manual Tasks and Physical Activities and Health Perceptions and Practices decreased the likelihood of High-Stable membership (relative to Low-Declining). Moderate/Normal-Declining membership was predicted by Social and Household Management (higher). For education, more years predicted High-Stable membership. Moderation analyses indicated that gender effects were consistent across both sexes and APOE carrier status.</p><p><strong>Conclusions: </strong>Data-driven analyses show that biological sex and measurable facets of gender differentially contribute to memory trajectory patterns over a 42-year span of cognitively unimpaired aging.</p>","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13085552/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147389111","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}