Biology of Sex Differences最新文献

{"title":"Applying a life course approach to elucidate the biology of sex differences in frailty: early-life gonadectomy diminishes late-life robustness in male and female dogs in the Exceptional Aging in Rottweilers Study.","authors":"David J Waters, Aimee H Maras, Rong Fu, Andres E Carrillo, Emily C Chiang, Cheri L Suckow","doi":"10.1186/s13293-025-00735-2","DOIUrl":"10.1186/s13293-025-00735-2","url":null,"abstract":"<p><strong>Background: </strong>Frailty refers to a state of increased vulnerability to mortality and other adverse outcomes as a consequence of age-related physiological decline. Sex differences in frailty have been reported; women are usually more frail than men. Physical frailty in men and women is the result of both sociobehavioral and biological factors, making the deciphering of the biology of sex differences in frailty challenging. Investigators have measured frailty in aging animals, including mice and dogs. We posited that companion dogs provide a useful opportunity to study sex differences in the biology of frailty, circumventing many of the sociobehavioral determinants of frailty that complicate human studies.</p><p><strong>Methods: </strong>Male-female differences in the relationship between lifetime gonad hormone exposure and late-life robustness were studied in the Exceptional Aging in Rottweilers Study (EARS), a lifetime cohort study of companion dogs with a broad range of lifetime gonad exposure. Late-life frailty was assessed by scoring dogs (135 females, 87 males) for deficit accumulation using a 34-item clinical frailty index previously developed and validated in dogs. The study outcome, late-life robustness, was defined as the lowest tertile of frailty index in the study population. Logistic regression models were constructed to assess differences in the likelihood of late-life robustness in dogs stratified into low, middle, and high lifetime gonad exposure groups. Male-female differences were probed after controlling for age at frailty scoring, gonad exposure, and other covariates.</p><p><strong>Results: </strong>In both male and female dogs, there was a strong association between longer lifetime gonad exposure and increased likelihood of late-life robustness. Compared to dogs in the lowest gonad exposure group, dogs with highest gonad exposure had a statistically significant 3-fold (females) to 10-fold (males) higher likelihood of late-life robustness. Notably, after controlling for gonad exposure and age at frailty scoring, no male-female difference in late-life robustness was found.</p><p><strong>Conclusions: </strong>The research extends current interest in the biology of sex differences in frailty and provides rationale for further inquiry into the role that the hypothalamic-pituitary-gonadal axis plays in supporting late-life robustness. Studies with companion dogs represent a unique investigative opportunity to enhance our understanding of biological factors that impact sex differences and to spur the development of sex-specific anti-frailty interventions.</p>","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":"16 1","pages":"52"},"PeriodicalIF":4.9,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12265119/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144648419","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":"Transcriptome analysis reveals the sex-switching mechanism of juvenile hermaphroditism in silver pomfret (Pampus argenteus).","authors":"Yaya Li, Jiabao Hu, Chongyang Wang, Man Zhang, Youyi Zhang, Yuanbo Li, Mengke Tang, Chunlai Qin, Zukang Feng, Shanliang Xu, Xiaojun Yan, Xubo Wang, Haimin Chen, Yajun Wang","doi":"10.1186/s13293-025-00736-1","DOIUrl":"10.1186/s13293-025-00736-1","url":null,"abstract":"<p><strong>Background: </strong>Our previous study on silver pomfret (Pampus argenteus) demonstrated that all gonads initially develop into ovaries by 60 days post-hatch (dph). Between 80 and 120 dph, some oocytes undergo apoptosis, resulting in the development of testes and a transient hermaphroditic stage. This observation indicates a complex molecular mechanism underlying sex differentiation in this species.</p><p><strong>Methods: </strong>Gonadal samples were collected at 90 dph, 120 dph, and 150 dph, with sex identification performed by HE staining and transcriptome sequencing. Morphological traits, including body length and weight, were measured to evaluate sexual size dimorphism. Candidate genes related to with sex differentiation were identified through differential gene expression analysis and feature selection methods, followed by gene set enrichment analysis to identify potential molecular pathways. Heatmaps were generated to visualize gene expression patterns across developmental stages and samples. Sex hormones concentrations were measured using commercial assay kits to assess their role in gonadal differentiation. RT-qPCR validated the sequencing results, while immunofluorescence (IF) examined the expression of related genes in testes and ovaries.</p><p><strong>Results: </strong>Histological and transcriptomic analyses identified the period between 90 and 120 dph as critical for sex differentiation in silver pomfret. At 90 dph, apoptotic signals trigger the apoptosis of early-stage oocytes. During this period, both testis-preferential and ovary-preferential genes exhibit high expression, leading to spermatogonia differentiation and the emergence of a juvenile hermaphroditic stage. The study established that androgens 11-KT and estrogen E2 regulate sex differentiation through modulation of related gene expression, with 11-KT serving a crucial role. This process involved significant enrichment of the steroid hormone biosynthesis pathway and the metabolism of xenobiotics by cytochrome P450 in the testes. Ovarian development is characterized by fatty acid metabolism and PPAR signaling pathway activation, along with energy metabolism pathways including the citrate cycle (TCA cycle) and cell degradation processes, such as lysosome activity and ubiquitin-mediated proteolysis, suggesting that ovarian development encompasses lipid accumulation and follicular selection.</p><p><strong>Conclusions: </strong>This investigation illuminates the molecular processes underlying this distinctive pattern of gonadal differentiation, providing novel insights into sex differentiation in fish exhibiting a juvenile hermaphroditic stage.</p>","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":"16 1","pages":"51"},"PeriodicalIF":4.9,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12261592/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144636028","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":"Alcohol use during pregnancy: the impact of social determinants of health on alcohol consumption among pregnant women.","authors":"MacKenzie R Peltier, Terril L Verplaetse, Vera Bici, Abbie A Mokwuah, C Leonard Jimenez Chavez, Yasmin Zakiniaeiz, Robert Kohler, Vernon Garcia-Rivas, Bubu A Banini, Hang Zhou, Nakul R Raval, Brian Pittman, Sherry A McKee","doi":"10.1186/s13293-025-00731-6","DOIUrl":"10.1186/s13293-025-00731-6","url":null,"abstract":"<p><strong>Background: </strong>There is no safe amount or time of alcohol consumption during pregnancy; however, many women drink while pregnant placing themselves and their fetuses at risk for alcohol-related health complications. Social Determinants of Health (SDoH) impact alcohol use during pregnancy. Understanding the impact of SDoH across pregnancy will elucidate important information to reduce rates of prenatal alcohol exposure.</p><p><strong>Methods: </strong>Cross-sectional data from the National Survey of Drug Use and Health from 2009 to 2019 was used to explore the impact of SDoH on alcohol use across pregnancy. The study assesses past month alcohol use and past month binge drinking, as well as various SDoH. The sample included 8,638 pregnant women.</p><p><strong>Results: </strong>Over 9% of pregnant women reported alcohol use within the past 30 days and 5.25% reported drinking on three or more days within the past month. 3.65% reported past month binge drinking. Past month alcohol use and past month binge drinking decreased in the second and third trimesters; however, a subset of women continued alcohol use, including binge drinking. Specific SDoH emerged as increasing the likelihood of alcohol use within the past month, including not being married (ORs = 1.54 to 1.94), criminal justice involvement (arrested and booked; OR = 1.88), and past year psychiatric distress (OR = 1.86). Conversely, other determinants were associated with a lower likelihood of alcohol use, including identifying as Asian or Hispanic (ORs = 0.41 and 0.64) and unemployment (OR = 0.52) and other employment (OR = 0.66). Older age was associated with a lower likelihood of binge drinking within the past month (ORs = 0.32). Unique SDoH emerged when examining alcohol use by trimester.</p><p><strong>Conclusion: </strong>Specific SDoH (i.e., not married, criminal justice involvement, past year psychiatric distress) are related to increased alcohol use during pregnancy, while other determinants (i.e., identifying as Asian or Hispanic, not requiring full time/part-time employment) are associated with a decreased risk for past month alcohol use. Older individuals (35-49 years old) and those with a high school education had a decreased likelihood of binge drinking. Accordingly, healthcare providers should screen all pregnant women for alcohol use throughout pregnancy, especially among populations or groups identified as being vulnerable to continue alcohol use during pregnancy.</p>","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":"16 1","pages":"49"},"PeriodicalIF":4.9,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12219128/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144537885","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 differences in endocrine, metabolic and psychological disturbance in obese patients with OSA.","authors":"Cheng Zi Qian, Zhang Li, Li Yi Ming, Han Teng, Su Lin Fan, Zhang Xiao Lei","doi":"10.1186/s13293-025-00730-7","DOIUrl":"10.1186/s13293-025-00730-7","url":null,"abstract":"<p><strong>Background: </strong>Obstructive sleep apnea (OSA) is associated with increased risks of glucolipid metabolic disruption, endocrine disturbances and psychological distress. There is scarce research regarding the influence of sex on these associations. The current study aimed to evaluate the effects of sex on metabolic, endocrine and psychological changes in patients with OSA.</p><p><strong>Methods: </strong>One hundred sixty-four young adult women and one hundred sixty-two age-matched men with OSA completed polysomnography assessments, questionnaires (including the Epworth Sleepiness Scale [ESS], Self-Reported Anxiety Scale [SAS], Self-Rating Depression Scale [SDS], and 12-Item Short-Form Health Survey [SF-12]) and biochemical analyses for glucolipid metabolism and endocrine function, including the pituitary-adrenal (PA), pituitary thyroid (PT), and pituitary-gonadal (PG) axes.</p><p><strong>Results: </strong>Homeostasis model assessment of insulin resistance (HOMA-IR), thyroid hormone and midnight PA axis activity levels were greater in female patients with severe OSA compared to those with mild-to-moderate OSA, and these metabolic and endocrine changes were associated with nocturnal hypoxia only in female patients. Additionally, midnight cortisol was associated with HOMA-IR (independent of anthropometry and sleep disturbance parameters) in females (β = 0.545, P = 0.012, adjusted R² = 0.217). ESS was higher for male patients with severe OSA compared to females with the same level of OSA (P = 0.003), and ESS was associated with nocturnal hypoxia in males (β = - 0.494, P = 0.001, adjusted R² = 0.224). SAS was higher for female patients with severe OSA compared to males with the same level of disease (P = 0.001).</p><p><strong>Conclusions: </strong>The metabolic, endocrine and psychological consequences of OSA may differ across sexes. The associations of nocturnal hypoxia with glucose metabolic disturbance and the activation of the PA and PT axes were observed in females, whereas the association of nocturnal hypoxia with ESS was limited to males. This could indicate a distinct metabolic, endocrine and psychological phenotype for female patients with OSA, who may require different disease management strategies compared to males.</p>","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":"16 1","pages":"48"},"PeriodicalIF":4.9,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12219881/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144537889","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":"A cross-species analysis of neuroanatomical covariance sex differences in humans and mice.","authors":"Linh Pham, Elisa Guma, Jacob Ellegood, Jason P Lerch, Armin Raznahan","doi":"10.1186/s13293-025-00728-1","DOIUrl":"10.1186/s13293-025-00728-1","url":null,"abstract":"<p><strong>Background: </strong>Structural covariance within the brain is thought to reflect inter-regional sharing of developmental influences. This hypothesis has proved difficult to test but can be informatively probed by the study of sex differences. Here, we use neuroimaging in humans and mice to study sex-differences in anatomical covariance- asking (1) are there sex differences in structural covariance and (2) do regions that share the same developmental influences, as exhibited by shared sex differences in volume, also show shared sex differences in volume covariance. This study design illuminates both the biology of sex-differences and theoretical models for anatomical covariance- benefitting from tests of inter-species convergence.</p><p><strong>Methods: </strong>Brain volume correlations for males and females across 255 regions in mice (n = 423) and 378 regions in humans (n = 436) were calculated using volumetric measures obtained from structural MRI. Mean correlations for each sex were compared within species to determine whether covariance sex differences exist. Specific covariances with strong sex differences in each species were identified via permutation tests for statistical significance. Brain maps of regional average structural covariance sex-bias were generated for mice and humans. Regional average structural covariance sex-bias and volumetric sex-bias were correlated to identify whether these features align in their direction of sex-bias.</p><p><strong>Results: </strong>We find that volumetric structural covariance is stronger in adult females than males for both wild-type mice and healthy human subjects: 98% of comparisons with statistically significant covariance sex differences in mice are female-biased, while 76% of such comparisons are female-biased in humans (q < 0.05). Regional covariance and volumetric sex-biases have weak inverse relationships to each other in both species: volumetrically male-biased regions contain more female-biased covariations, while volumetrically female-biased regions have more male-biased covariations (mice: r = -0.185, p = 0.002; humans: r = -0.189, p = 0.001).</p><p><strong>Conclusions: </strong>Our results identify a tendency for females to show stronger neuroanatomical covariance across species. These structural covariance sex differences are also partially related to regional sex differences in volume for both species, suggesting that stronger structural covariance in females could be an evolutionarily conserved feature - partially shaped by the same developmental influences that mediate volumetric sex-biases.</p>","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":"16 1","pages":"47"},"PeriodicalIF":4.9,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12220812/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144537884","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":"Associations of street-view greenspace exposure with cardiovascular health (Life's Essential 8) among women in midlife.","authors":"Sheryl L Rifas-Shiman, Li Yi, Izzuddin M Aris, Pi-I Debby Lin, Marie-France Hivert, Jorge E Chavarro, Esra Suel, Peter James, Emily Oken","doi":"10.1186/s13293-025-00718-3","DOIUrl":"10.1186/s13293-025-00718-3","url":null,"abstract":"<p><strong>Background: </strong>Many women experience suboptimal cardiovascular health (CVH) during midlife. Greenspace exposure has been inversely associated with cardiovascular disease because it may reduce harmful environmental exposures and promote healthy behaviors. Most prior studies used satellite-based rather than ground-level exposures and did not examine overall CVH.</p><p><strong>Methods: </strong>We performed a longitudinal analysis of women in the Project Viva cohort based in Eastern Massachusetts. We applied deep learning algorithms to Google Street View images to derive metrics of visible trees, grass, and other greenspace within 500 m of participant's residential addresses in 2012-2016 (mean age 46 years). About five years later (mean age 51 years), participants completed questionnaires and research measurements including blood collection. We calculated CVH scores using Life's Essential 8 (LE8) construct (0-100 points, higher = better), which includes four behavioral (diet, physical activity, sleep, and avoidance of smoking) and four biomedical measures (body mass index, blood pressure, blood lipids, and blood glucose). We used linear regression models adjusted for age and both individual- and neighborhood-level socioeconomic status.</p><p><strong>Results: </strong>Among 767 participants, 68% were non-Hispanic White, and 74% were college graduates. Mean (SD) CVH score was 72 (13) points. When including three greenspace components in the same model, higher % trees (per SD) was associated with higher overall CVH score (β = 2.4; 95% CI: 1.3, 3.5), as well as higher behavioral (β = 2.8; 95% CI: 1.4, 4.3) and biomedical (β = 2.8; 95% CI: 1.0, 4.7) sub-scores. Additionally, % other greenspace (per SD) was associated with better biomedical CVH scores (β = 2.2; 95% CI: 0.4, 3.9), whereas associations for % grass were non-significant. Higher % trees (per SD) was associated with higher scores for most individual CVH components, including diet (β = 2.1 points; 95% CI: 0.7, 3.4), physical activity (β = 4.0; 95% CI: 1.2, 6.9), sleep (β = 2.6; 95% CI: 0.9, 4.4), BMI (β = 5.8; 95% CI: 2.8, 8.8), and blood glucose (β = 2.2; 95% CI: 0.3, 4.2).</p><p><strong>Conclusions: </strong>Greater street-view greenspace exposure, especially visible trees in streetscapes, was associated with better CVH among midlife women. Increasing trees in neighborhoods may be a valuable public health strategy to improve multiple metrics of cardiovascular health.</p>","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":"16 1","pages":"45"},"PeriodicalIF":4.9,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12219997/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144537886","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":"Lifetime history of hypertensive disorders of pregnancy is associated with shorter sleep duration and more sleep disturbance in midlife: results from the Project Viva women's health cohort.","authors":"Kimia Heydari, Sheryl L Rifas-Shiman, Suzanne M Bertisch, Elizabeth B Klerman, Jorge E Chavarro, Emily Oken, Karen M Switkowski","doi":"10.1186/s13293-025-00725-4","DOIUrl":"10.1186/s13293-025-00725-4","url":null,"abstract":"<p><strong>Background: </strong>Hypertensive disorders of pregnancy (HDP) are associated with worse prenatal and perinatal sleep health and higher cardiovascular disease risk beyond the peripartum period. The relationship of HDP with sleep health in midlife, when sleep problems are common, remains unclear.</p><p><strong>Methods: </strong>We studied women enrolled in Project Viva during early pregnancy (1999-2002) with sleep outcomes assessed in midlife (2017-2024). We determined lifetime HDP via medical records from the index pregnancy and self-report both at enrollment and during midlife. Outcomes were (i) self-reported sleep duration and sleep quality, using the patient-reported outcomes measurement information system sleep disturbance and sleep-related impairment instruments at mean 52.3yrs; and (ii) objectively measured 5-day sleep duration and efficiency by wrist actigraphy at mean 55.8yrs in a subset. We performed linear and logistic regression models adjusted for enrollment age, education, parity, household income, pre-pregnancy BMI, race, and ethnicity and considered modification by social determinants of health.</p><p><strong>Results: </strong>Of 767 participants, 23% had a lifetime history of HDP, 4% had ≥ 2 episodes, and 7% had HDP during their last pregnancy. Mean (SD) daily sleep duration was 7.1 (1.0) hours by self-report and 6.7 (1.0) hours by actigraphy. Any (vs. no) lifetime HDP was associated with shorter self-reported (-8 min, 95% CI: -19, 2) and actigraphy-measured (-16 min, 95% CI: -31, -1) sleep duration. Estimates were stronger but with wider CIs for those with ≥ 2 (vs. no) HDP episodes (e.g., -23 min, 95% CI: -53, 6 for actigraphy-measured sleep duration). Mean (SD) sleep disturbance T-score was 48.6 (7.4) and sleep-related impairment was 45.8 (8.5). Any lifetime HDP (vs. none) was associated with higher (worse) sleep disturbance T-score (1.85 points, 95% CI: 0.28, 3.42) with stronger associations for ≥ 2 HDP episodes (3.41 points, 95% CI: 0.17, 6.65) and for HDP in the last pregnancy (3.63 points, 95% CI: 0.70, 6.57). HDP was not associated with self-reported sleep-related impairment or sleep efficiency.</p><p><strong>Conclusions: </strong>History of HDP was associated with shorter sleep duration and higher sleep disturbance in midlife. Future work should investigate the contribution of sleep health to associations of HDP exposure with cardiovascular disease risk in later life.</p>","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":"16 1","pages":"46"},"PeriodicalIF":4.9,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12219990/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144537888","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":"Interindividual and sex differences in resilience and vulnerability to post-traumatic stress disorder (PTSD): insights from animal models.","authors":"Giulia Federica Mancini, Sebastiano Alfio Torrisi, Eva Myriam Goussivi Viho, Onno Cornelis Meijer, Gian Marco Leggio, Patrizia Campolongo","doi":"10.1186/s13293-025-00732-5","DOIUrl":"10.1186/s13293-025-00732-5","url":null,"abstract":"<p><p>Stress triggers many responses including behavioral strategies to cope with the environment and to maintain homeostasis. Notably, the experience of stressful events is highly subjective. In fact, in susceptible individuals, primary adaptation responses can fail leading to maladaptive mechanisms and to the subsequent development of stress-related disorders (e.g., post-traumatic stress disorder; PTSD). However, the mechanisms underlying interindividual variability in stress adaptation are still to be elucidated. Animal models are widely recognized as essential scientific tools to understand the neurobiological underpinnings of stress susceptibility/resilience, and as tools to identify novel and personalized interventions to treat (and prevent) such disorders in humans. Experimental models have however several limitations, as validity criteria can be very problematic when modeling psychiatric disorders. Also, while sex dimorphism crucially contributes to the risk for stress-related diseases, several frequently used models overlooked sex differences in the interindividual variability in response to stress. In this review, we describe the interindividual and sex differences in susceptibility and resilience in stress-related disorders, with a particular focus on PTSD. Further, we examine aspects of animal models of PTSD that can be improved to obtain higher translational value.</p>","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":"16 1","pages":"50"},"PeriodicalIF":4.9,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12219389/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144537887","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 serum testosterone and measures of cardiovascular health among transgender individuals using gender-affirming testosterone therapy: a cross-sectional study.","authors":"Badal S B Pattar, Tyrone G Harrison, Nathalie Saad, Sandra M Dumanski, A J Lowik, Paul E Ronksley, Dina N Greene, Cameron T Whitley, Chantal L Rytz, Keila Turino Miranda, Lindsay Peace, Amelia M Newbert, Darlene Y Sola, Sofia B Ahmed","doi":"10.1186/s13293-025-00726-3","DOIUrl":"10.1186/s13293-025-00726-3","url":null,"abstract":"<p><strong>Background: </strong>Gender-affirming testosterone therapy (GATT) use may be associated with increased systolic blood pressure (SBP). The association between serum testosterone and cardiovascular health in individuals using GATT is unknown. The objective of this study was to estimate the association between serum testosterone and validated measures of cardiovascular health, including SBP and arterial stiffness, in persons assigned female sex at birth using GATT.</p><p><strong>Methods: </strong>Healthy participants assigned female sex at birth on a stable GATT regimen for ≥ 4 months were recruited to this community-partnered exploratory cross-sectional study. Exposures of interest were total and free serum testosterone concentration. As our primary outcome, SBP was measured by an automated sphygmomanometer, and carotid-radial pulse wave velocity (PWVcr) and aortic augmentation index (AIx) were used to measure arterial stiffness via applanation tonometry.</p><p><strong>Results: </strong>Participants (n = 18, median age 28 years, range: 18, 50) who predominantly self-identified as white (94%) and had been using GATT for a median of 48 months (range: 5, 84) were studied. Resting SBP, PWVcr, and AIx were 113 mmHg (range: 102, 129), 7 m/s (range: 4, 9), and 9% (range: - 10, 23), respectively. Total and free serum testosterone were not significantly associated with SBP or PWVcr. Free, but not total, serum testosterone was positively associated with AIx (p = 0.03). Sensitivity analyses did not modify any results.</p><p><strong>Conclusions: </strong>In healthy transgender individuals, serum testosterone concentrations may not be associated with measures of cardiovascular health. However, these results need to be interpreted with caution given the limited sample size.</p>","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":"16 1","pages":"44"},"PeriodicalIF":4.9,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12172241/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144315808","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":"Psychosocial and clinical characteristics in Takotsubo syndrome.","authors":"Okezi Obrutu, Yujie Cui, Jenna Maughan, Paul Marano, Janet Wei, Martha Gulati, Marie Lauzon, Romana Herscovici, Chrisandra Shufelt, Natalie Rojas, Benita Tjoe, Thomas Rutledge, C Noel Bairey Merz","doi":"10.1186/s13293-025-00729-0","DOIUrl":"10.1186/s13293-025-00729-0","url":null,"abstract":"<p><strong>Background: </strong>Takotsubo Syndrome (TTS) is an acute form of heart failure that disproportionately impacts post-menopausal women. The brain-heart connection is considered a pathway for TTS pathophysiology leading to investigations of the role of psychological, psychosocial, and personality factors in TTS.</p><p><strong>Objectives: </strong>We compare psychosocial characteristics among a subset of individuals with confirmed TTS and those who had symptoms adjudicated as non-TTS in our online Takotsubo registry (n = 104). We also evaluate differences in TTS clinical characteristics among those with and without symptoms of PTSD and depression.</p><p><strong>Methods: </strong>The Smidt Heart Institute Takotsubo registry enrolls individuals with a history of TTS sourced through physician referrals, medical records review, peer- and self-referrals. Psychosocial characteristics were assessed using questionnaires validated in acute coronary syndrome populations. Hedge's g effect sizes were computed to compare differences in perceived stress, depression symptoms, and post-traumatic stress disorder (PTSD) symptoms relative to TTS status.</p><p><strong>Results: </strong>Compared to participants confirmed to be non-TTS, those with adjudication-confirmed TTS had worse mean psychosocial scores (indicative of worse psychosocial characteristics). After adjusting for age at event, BMI, race, and smoking status, the Hedge's g effect size for depressive symptoms was moderate [0.60 (-0.03, 1.22)] while effect sizes for other psychosocial measures were minimal (Trait anxiety: [0.01 (-0.58, 0.60)], PTSD symptoms [0.13 (-0.46, 0.73)], perceived stress [0.06 (-0.53, 0.65)]. Effect sizes were relatively lower following adjustment, largely driven by participants' age at first event. Individuals with elevated PTSD symptoms were significantly younger at their first TTS event compared to those with minimal or no symptoms (54 ± 8 vs. 61 ± 10; p = 0.005). QTc was relatively longer among individuals with elevated PTSD symptoms (483 ± 40 msec vs. 465 ± 32 msec; p = 0.08) and elevated depressive symptoms (481 ± 33 msec vs. 464 ± 36 msec; p = 0.07), although the differences were not statistically significant.</p><p><strong>Conclusions: </strong>Psychosocial characteristics including PTSD, depression, and stress are common among women with TTS, and age at the time of TTS event is a potentially important moderator of this relationship. We did not find Trait-anxiety or early childhood trauma to be associated with TTS in our cohort.</p>","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":"16 1","pages":"42"},"PeriodicalIF":4.9,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12168290/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144309503","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}