NIH SCORE centers showcase sex differences research spanning heart, brain, pregnancy and immunity

The Office of Research on Women’s Health at the National Institutes of Health has published the scientific abstracts from its Specialized Centers of Research Excellence, or SCORE, program on sex differences, timed to the program’s 2025 annual meeting held on March 17, 2026, at the Natcher Conference Center on the NIH Bethesda campus in Maryland. The collection, appearing in BMC Proceedings, gathers plenary talks and poster presentations from twelve active SCORE centers across the United States, each co-funded by the ORWH and partner NIH institutes under an annual investment exceeding 18 million dollars. The meeting carried the theme “From the Bench to the Health of the Nation,” and included a keynote from Dr. Jill Becker of the University of Michigan, whose presentation is available through NIH Videocast.

The SCORE program operates through a U54 cooperative agreement and is co-funded by eight NIH institutes and centers: the National Heart, Lung, and Blood Institute; the National Institute on Aging; the National Institute on Alcohol Abuse and Alcoholism; the National Institute of Arthritis and Musculoskeletal and Skin Diseases; the National Institute on Drug Abuse; the National Institute of Diabetes and Digestive and Kidney Diseases; the National Institute of Environmental Health Sciences; and the National Institute of Mental Health. Its stated objective is to accelerate new knowledge about diseases that affect women, deepen understanding of their causes, and improve strategies for treatment and prevention. Program leaders emphasize that the centers serve as national resources for translational research and that a newly introduced Career Enhancement Core supports pilot projects and trains the next generation of scientists. According to the introduction, the ORWH SCORE program remains the only NIH specialized center program supporting disease-agnostic research on sex differences, building on more than two decades of prior investment.

Several abstracts address cardiovascular health, where sex differences shape both disease progression and treatment response. Researchers at Augusta University described an outreach project designing illustrated educational materials in English and Spanish to improve cardiovascular knowledge among women in the rural South-East of the United States, where low health literacy raises morbidity and mortality by 1.71 times among rural patients. In 2024 and 2025 the team reached more than 3,000 individuals in Georgia and South Carolina, distributing postcards, bookmarks, stickers and posters alongside blood pressure checks at farmers markets, schools and health events. Panels at a culturally aware educational exhibit received average clarity scores between 4.8 and 5.0 on a five-point scale, and future work will evaluate exhibitions paired with blood pressure cuffs available for checkout in rural libraries, an effort already begun in Hancock County, Georgia.

At Cedars-Sinai Medical Center, investigators with the MAE-WEST SCORE tested a Unified Structural and Functional Connectivity model in women with suspected ischemia due to coronary microvascular dysfunction from the WISE cohort. Using multimodal neuroimaging and machine learning, they found that the integrated model outperformed structural or functional connectivity alone in predicting outcomes ranging from crystallized cognition to coronary endothelial function and myocardial perfusion reserve. Connections between the caudate and medial frontal cortex emerged as the strongest cognitive predictors, while visual and thalamic pathways were associated with cardiac health indices, supporting the framework as a potential biomarker platform for neuro-cardiac syndromes linked to microvascular dysfunction.

Metabolic and hormonal mechanisms featured prominently among the preclinical reports. A team at the University of South Carolina proposed skeletal muscle-derived estrogen as a therapeutic target for type 2 diabetes, reporting preliminary data that aromatase overexpression in mouse muscle increases muscle mass, enhances fatty acid oxidation and reduces adiposity, while estrogen receptor-alpha deletion in muscle promotes muscle loss and fat accumulation. Estrogen upregulated muscle pyruvate carboxylase, suggesting a novel mechanism for fat oxidation that the group plans to probe with inducible deletion and overexpression models. Separately, UCLA researchers using the Four Core Genotypes mouse model, which separates chromosomal sex from gonadal sex, found that XX mice regardless of gonadal type showed greater diastolic dysfunction and metabolic stress in a heart failure with preserved ejection fraction model, implicating sex chromosome complement itself in the sex bias of this condition. A companion study from the same group reported that time-restricted feeding, confining calories to a nine-hour active-phase window, protected both male and female mice against diet-induced HFpEF independent of caloric intake, suppressing gene programs tied to inflammation, fibrosis and hypertrophy.

Reproductive biology and pregnancy emerged as another major theme. Investigators at Brigham and Women’s Hospital and Harvard Medical School described ongoing plasma proteomic profiling studies building on their previous finding that pregnancy induces a transient but reproducible acceleration in biological age as measured by DNA methylation biomarkers, a result validated by multiple independent research groups. The new work applies organ-specific aging signatures to understand how biological systems respond to pregnancy, with attention to maternal age and the integration of clinical outcomes to identify molecular signatures of pregnancy complications. At UCLA, a separate team showed that estrogen-sensitive neurons in the preoptic area of the hypothalamus coordinate pregnancy-induced thermoregulatory adaptations, with chemogenetic inhibition of these neurons producing transient increases in maternal core temperature and elimination of estrogen receptor alpha expression raising temperature at the end of gestation, findings that illuminate how estrogens act on the brain to fine-tune physiology during reproduction.

Preeclampsia research from the Mississippi collaborative detailed three distinct animal models replicating human disease features, including placental ischemia, maternal endothelial dysfunction and fetal growth restriction with offspring hypertension. The center’s stated premise is that despite preeclampsia being a leading cause of maternal death, no effective drug treatment exists to prevent or delay its progression, leaving early delivery as the only effective intervention. The program’s four projects aim to examine relevant factors in clinical populations of preeclamptic and normotensive women and their children while using cellular, molecular, physiological and pharmacological tools in animal models to identify therapeutic targets and long-term cardiovascular consequences.

Neuropsychiatric investigations occupied a substantial share of the meeting program. Massachusetts General Hospital researchers reported sex-selective deficits in connectivity of circuitry regulating inhibitory control of arousal in major depressive disorder, particularly in women, associated with reduced heart rate variability, reproductive aging, pro-inflammatory cytokine expression and adverse maternal prenatal immune activation. In a randomized trial of respiratory-gated auricular vagal afferent nerve stimulation, sixty-two participants with recurrent remitted depression underwent functional MRI during stimulation; active stimulation produced significantly greater activation in the left hippocampus and anterior prefrontal cortex in women, alongside an increase in the high-frequency component of heart rate variability, while no significant effects appeared in men. A related observational study of 108 midlife adults found a group-by-sex interaction in amygdala-ventromedial prefrontal cortex connectivity, with hypoconnectivity in depressed women versus healthy controls and hyperconnectivity in depressed men, and lower high-frequency heart rate variability in depressed women specifically, underscoring the need for sex-selective treatment in midlife.

Immune and infectious disease research also featured prominently. Stanford’s SCORE-X program presented work on XIST, the long noncoding RNA expressed exclusively in cells with two X chromosomes, which forms an immunogenic ribonucleoprotein complex. Enforced expression of XIST ribonucleoprotein in males sufficed to confer female-level autoimmunity in a mouse model of systemic lupus erythematosus, and patients with lupus, scleroderma and other female-biased autoimmune diseases show elevated anti-XIST antibodies with distinct patterns across conditions. A follow-up abstract mapped autoantibody targets to discrete hotspots along the 19-kilobase XIST RNA and identified a novel anti-SPEN hotspot antibody linked to disease severity and a vasculopathic phenotype in systemic sclerosis. Emory University investigators reported that greater childhood maltreatment was associated with higher peripheral lipopolysaccharide levels irrespective of HIV status, and that peripheral blood mononuclear cells from women with HIV showed more estradiol-induced differentially expressed genes than those from women without HIV, sixteen versus four, with gene ontology analyses pointing to the TNF signaling pathway. A separate cross-sectional study of 68 women living with HIV found that bone mineral density Z-scores were associated with metabolites enriched in arachidonic acid, fatty acid oxidation, energy metabolism and steroid hormone pathways, with menopausal status modifying several of these associations.

Substance use research rounded out the meeting’s scope. The Medical University of South Carolina described preclinical studies using a vaporized cannabis exposure model across the lifespan, finding that female rats self-administer more tetrahydrocannabinol than males during emerging and late adulthood, that THC vapor induces cognitive deficits in both sexes that recover with abstinence, and that sex- and age-related lipidome changes appear in serum and hippocampal tissue. A clinical survey of peripartum cannabis use found that while 72 percent of providers universally assess cannabis use, fewer than a quarter sometimes or often refer for evaluation or treatment, and most patients reduced or stopped use in pregnancy without any support. Yale investigators analyzing the 2021 and 2023 National Youth Risk Behavior Survey reported that higher drinking frequency and greater peak drinking intensity were each associated with increased odds of passive suicidal ideation among adolescents, with girls showing higher odds than boys, and that significant sex-by-alcohol interactions for suicide attempts indicated higher levels of alcohol use were associated with more attempts among adolescent girls. Together, the abstracts illustrate the breadth of the SCORE portfolio, from molecular mechanisms of X chromosome escape and gut microbial estrogen recycling to behavioral interventions and community health outreach, all unified by the premise that studying both sexes yields insights that improve treatment for everyone.

Subject of Research: Sex differences research presented at the NIH Specialized Centers of Research Excellence 2025 annual meeting

Article Title: Abstracts from Specialized Centers of Research Excellence (SCORE) on Sex Differences 2025 annual meeting

Article References: Abstracts from Specialized Centers of Research Excellence (SCORE) on Sex Differences 2025 annual meeting. (2026). BMC Proceedings, 20(23), 28. https://doi.org/10.1186/s12919-026-00381-5 (Author names are not included in the publisher’s citation export.)

Image Credits: AI Generated

DOI: 10.1186/s12919-026-00381-5

Keywords: sex differences, NIH, SCORE program, women's health, cardiovascular disease, autoimmunity, preeclampsia, HIV, major depressive disorder, biological aging, cannabis research, XIST RNA