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We identified differentially expressed genes comparing peritoneal endometriosis lesions (n = 18), eutopic endometrium (n = 17), and peritoneum (n = 22) from the same patients with complete menstrual cycles using microarrays (54 675 probe sets) and immunohistochemistry. Peritoneal lesions and peritoneum demonstrated 3901 and 4973 significantly differentially expressed genes compared to eutopic endometrium, respectively. Peritoneal lesions significantly revealed no correlation with a specific menstrual cycle phase by gene expression and histopathology, exhibited low expressed proliferation genes, and constant levels of steroid hormone receptor genes. Tissue remodeling genes in cytoskeleton, smooth muscle contraction, cellular adhesion, tight junctions, and O-glycan biosynthesis were the most significant to lesions, including desmin and smooth muscle myosin heavy chain 11. Protein expression and location of desmin, alpha-actin, and h-caldesmon in peritoneal lesions discriminated between smooth muscle hyperplasia and metaplasia. Peritoneal lesions demonstrate no menstrual cycle phasing but constant steroid hormone receptor expression where a slow but steady growth is linked with tissue remodeling. Our study contributes to the molecular pathology of peritoneal endometriosis and will help to identify clinical targets for treatment and management. [ABSTRACT FROM PUBLISHER]

Diastole is the sequence of physiological events that occur in the heart during ventricular filling and principally depends on myocardial relaxation and chamber stiffness. Abnormal diastolic function is related to many cardiovascular disease processes and is predictive of health outcomes, but its genetic architecture is largely unknown. Here, we use machine learning cardiac motion analysis to measure diastolic functional traits in 39,559 participants of the UK Biobank and perform a genome-wide association study. We identified 9 significant, independent loci near genes that are associated with maintaining sarcomeric function under biomechanical stress and genes implicated in the development of cardiomyopathy. Age, sex and diabetes were independent predictors of diastolic function and we found a causal relationship between genetically-determined ventricular stiffness and incident heart failure. Our results provide insights into the genetic and environmental factors influencing diastolic function that are relevant for identifying causal relationships and potential tractable targets., Competing Interests: Competing interests The authors declare no competing interests.