Cardiovascular disease (CVD) is the leading cause of death among women globally. Recognition of sex-specific risk factors, pathophysiology, and clinical presentations has established women's cardiovascular health as a research and clinical priority. Pregnancy complications, premature menopause, and autoimmune disease, are now identified as long-term contributors to cardiovascular risk, while female-predominant syndromes such as ischemia with non-obstructive coronary arteries and heart failure with preserved ejection fraction are increasingly acknowledged. Novel therapies and updated guidelines emphasize psychosocial determinants, reproductive history, and postpartum risk assessment in prevention and management. Despite these advances, women remain underdiagnosed, undertreated, and underrepresented in clinical trials. Diagnostic delays and limited access to therapies and rehabilitation persist globally, with disparities pronounced in Saudi Arabia, where obesity, diabetes, and hypertension are highly prevalent. Closing these gaps requires sustained investment in sex-specific research, equitable access to evidence-based care, and integration of women's cardiovascular health into national strategies under Saudi Vision 2030.

Biallelic variants in HSD17B4 cause D-bifunctional protein (DBP) deficiency, a disorder of peroxisomal fatty acid β-oxidation initially associated with a neonatal phenotype and early lethality. Recently, thanks to advances in genetic analyses, the clinical spectrum has expanded to include a slowly progressive adult-onset ataxic syndrome with additional features. Our aim was to describe 5 additional affected adults and to highlight the characteristic phenotype.

Cardiovascular disease is the leading cause of mortality among postmenopausal women in the European region. While women share traditional cardiovascular risk factors with men, the prevalence and impact on the cardiovascular system of these factors differ by gender. Moreover, women-specific risk factors have recently been identified, including premature or early-onset menopause, migraine, polycystic ovary syndrome, infertility, hypertensive disorders of pregnancy, gestational diabetes and endometriosis. This review details the example of three French gynecological-cardiological care pathways addressing these issues. The first example, based at Cochin-Hôtel-Dieu Hospital in Paris, is a gynecological and cardiological pathway focusing on women with premature ovarian failure, perimenopause, or menopause. The results reveal that over half of women assessed had either at least one new diagnosis of a major risk factor (hypertension, diabetes or dyslipidemia), or adjustments of their treatment. The second example is Menopause Center in Toulouse, assessing women aged 45 to 60. The assessment found that 35% had a single risk factor and another 35% had two or more traditional cardiovascular risk factors. The third example is the Women's Cardiovascular Healthcare Foundation, a mobile unit that visits 20 cities across France to carry out cardiac and gynecological screening, specifically targeting those in precarious situations. The results show that 90.2% of women had more than two cardiovascular risk factors. All these findings highlight the urgent need to address women's cardiovascular health. Collaboration between gynecologists and cardiologists could be strengthened to become a highly effective strategy for improving the cardiovascular health of women.

R-loops, though implicated in genome stability, have poorly defined transcriptional roles due to confounding replication processes in proliferating cells. Here, by leveraging replication-free oocytes and RTACC-seq, a tailored high-specificity R-loop mapping approach for low-input samples, we identify dynamic R-loop enrichment at both gene promoters and distal transposable elements. We find that transposable element-associated R-loops accumulate in transcriptionally active stage oocytes and resolve in fully grown oocytes, coinciding with chromatin condensation and transcriptional silencing. R-loops exert opposing, location-dependent regulatory functions, with reduced transcription rate at promoters and enhanced rates at transposable elements, raising the possibility of enhancer-like activity at a subset of hybrid-associated transposable element loci. In mice, oocyte-specific deletion of Rnaseh1, a gene that encodes an RNA:DNA hybrid-specific endonuclease, leads to persistent R-loops, chromatin decondensation, and impaired transcriptional silencing in fully grown oocytes, culminating in premature ovarian failure and female subfertility. These findings characterize the mechanistic basis of R-loops as mediators of chromatin remodeling, transcriptional regulation, and germ cell developmental competence.

Using nationally representative data from female participants in NHANES 2005-2018, this study evaluated the association between urinary volatile organic compound (VOC) metabolites and premature menopause and explored potential mechanisms using epidemiological analyses, mixture models, network toxicology, and experimental validation. Multivariable logistic regression and restricted cubic spline models were applied to assess the relationships between 18 urinary VOC metabolites and the risk of premature menopause. Multiple metabolites were associated with increased risk, among which N-acetyl-S-(2-hydroxyethyl)-L-cysteine (HEMA) showed the largest effect estimate in the fully adjusted model (OR = 1.47, 95% CI: 1.15-1.88) and a nonlinear exposure-response relationship. Mixture analyses showed that the overall VOC mixture was positively associated with premature menopause risk in WQS regression (OR = 1.58, 95% CI: 1.08-2.33) and quantile g-computation (OR = 1.51, 95% CI: 1.32-1.72), while BKMR showed a positive joint exposure-response pattern. HEMA had the largest WQS weight (0.388) and the largest positive weight in quantile g-computation. Network toxicology focusing on HEMA-related parent compounds identified targets enriched in DNA damage response and apoptosis-related pathways, with OGG1, CASP3, BCL2, and JUN emerging as hub genes. In a premature menopause-like mouse model, immunohistochemistry showed increased ovarian expression of OGG1, CASP3, and JUN and decreased BCL2 expression. Molecular docking provided preliminary structural compatibility evidence for possible HEMA-hub protein interactions. Together, this multi-level and multi-method evidence links environmental VOC exposure, represented by HEMA, to female reproductive functional decline and provides new support for environmental risk identification in premature menopause.

Premature ovarian insufficiency (POI) impairs fertility and health in reproductive-age women, with autoimmune factors contributing to 4-30% of cases. To investigate immune dysregulation in POI, we developed two mouse models using pZP3 induction: regular immune (RE-POI) and enhanced immune (EN-POI) cycles. The EN-POI model exhibited stable, irreversible ovarian dysfunction, including disrupted estrous cycles, hormonal changes (elevated FSH, decreased AMH, and estradiol), follicular depletion, and infertility. Immune profiling demonstrated consistent T-lymphocyte imbalance across both RE-POI and EN-POI model groups, characterized by expanded splenic CD4+ T cells, diminished regulatory T cells, elevated systemic inflammatory cytokines, and ovarian fibrosis. Proteomic comparison between the control and EN-POI groups identified 198 differentially expressed proteins, mainly enriched in immune and inflammatory pathways. Based on these differential proteins, subsequent network analysis further identified six key hub proteins, namely Mmp9, Isg15, Ikbke, Siglec1, Pf4, and Cdkn1b. This study establishes a stable autoimmune POI model, elucidates T-cell imbalance with cytokine storm and fibrosis, and identifies key molecules linking immune abnormalities to ovarian failure, offering new insights into POI research.