Context: Aberrant estrogen synthesis and metabolism have been suggested to increase local estradiol (E2) concentration in endometriosis and thus to promote the growth of the lesions. However, tissue estrogen concentrations within the endometrium and different types of endometriosis lesions have not been described. Objective: The aim of the study was to evaluate local E2 and estrone (E1) concentrations in the endometrium and different types of endometriosis lesions, and to correlate them with the expression of estrogen-metabolizing enzymes. Patients: Patients with endometriosis (n = 60) and healthy controls (n = 16) participated in the study. Main Outcome Measures: We measured serum and tissue concentrations of E2 and E1 as well as mRNA expression of the estrogen-metabolizing enzymes. Results: Endometrial or endometriotic intratissue E2 concentrations did not reflect the corresponding serum levels. In the proliferative phase, endometrial E2 concentration was five to eight times higher than in the serum, whereas in the secretory phase the E2 concentration was about half of that in the serum. Accordingly, a markedly higher E2/E1 ratio was observed in the endometrium at the proliferative phase compared with the secretory phase. In the endometriosis lesions, E2 levels were predominating over those of E1 throughout the menstrual cycle. Among the hydroxysteroid (17β) dehydrogenase (HSD17B) enzymes analyzed, HSD17B2 negatively correlated with the E2 concentration in the endometrium, and HSD17B6 was strongly expressed, especially in the deep lesions. Conclusions: Endometrial or endometriotic tissue E2 concentrations are actively regulated by local estrogen metabolism in the tissue. Thus, the inhibition of local E2 synthesis is a valid, novel approach to reduce local E2-dependent growth of endometriotic tissue.

Endometriosis is a common inflammatory estrogen-dependent gynecological disorder, associated with pelvic pain and reduced fertility in women. Several aspects of this disorder and its cellular and molecular etiology remain unresolved. We have analyzed the global gene expression patterns in the endometrium, peritoneum and in endometriosis lesions of endometriosis patients and in the endometrium and peritoneum of healthy women. In this report, we present the EndometDB, an interactive web-based user interface for browsing the gene expression database of collected samples without the need for computational skills. The EndometDB incorporates the expression data from 115 patients and 53 controls, with over 24000 genes and clinical features, such as their age, disease stages, hormonal medication, menstrual cycle phase, and the different endometriosis lesion types. Using the web-tool, the end-user can easily generate various plot outputs and projections, including boxplots, and heatmaps and the generated outputs can be downloaded in pdf-format.Availability and implementationThe web-based user interface is implemented using HTML5, JavaScript, CSS, Plotly and R. It is freely available from https://endometdb.utu.fi/.

The final maturation of spermatozoa produced in the testis takes place during their passage through the epididymis. In this process, the proteins sec

Hydroxysteroid (17β) dehydrogenases (HSD17Bs) form an enzyme family characterized by their ability to catalyze reactions in steroid and lipid metabolism. In the present study, we characterized the phenotype of HSD17B13‐knockout (HSD17B13KO) mice deficient in Hsd17b13. In these studies, hepatic steatosis was detected in HSD17B13KO male mice, indicated by histologic analysis and by the increased triglyceride concentration in the liver, whereas reproductive performance and serum steroid concentrations were normal in HSD17B13KO mice. In line with these changes, the expression of key proteins in fatty acid synthesis, such as FAS, acetyl‐CoA carboxylase 1, and SCD1, was increased in the HSD17B13KO liver. Furthermore, the knockout liver showed an increase in 2 acylcarnitines, suggesting impaired mitochondrial β‐oxidation in the presence of unaltered malonyl CoA and AMPK expression. The glucose tolerance did not differ between wild‐type and HSD17B13KO mice in the presence of lower levels of glucose 6‐phosphatase in HSD17B13KO liver compared with wild‐type liver. Furthermore, microgranulomas and increased portal inflammation together with up‐regulation of immune response genes were observed in HSD17B13KO mice. Our data indicate that disruption of Hsd17b13 impairs hepatic‐lipid metabolism in mice, resulting in liver steatosis and inflammation, but the enzyme does not play a major role in the regulation of reproductive functions.—Adam M., Heikelä H., Sobolewski, C., Portius, D., Mäki‐Jouppila J., Mehmood, A., Adhikari, P., Esposito, I., Elo, L. L., Zhang, F.‐P., Ruohonen, S. T., Strauss, L., Foti, M., Poutanen M. Hydroxysteroid (17β) dehydrogenase 13 deficiency triggers hepatic steatosis and inflammation in mice. FASEB J. 32, 3434–3447 (2018). www.fasebj.org

Epididymal proteins interact with sperm during their passage through the epididymis and thus contribute to the maturation and fertilizing capacity of the spermatozoa. In the present study we have discovered five novel epididymis-specific genes through in silico analysis of expressed sequence tags (ESTs) at the UniGene library collection. The strategy used is a powerful way to discover novel epididymis-specific genes. The full-length cDNA sequences were determined, and computational tools were used to characterize the genomic structures and to predict putative functions for the encoded proteins. In vitro analyses revealed that all five genes characterized were highly expressed in the defined areas of the epididymis, and they were not expressed at significant levels in any other tissue. Three of the genes were named on the basis of their putative functions: Spint4 (serine protease inhibitor, Kunitz type 4), and Rnase9 and Rnase10 (ribonuclease, Rnase A family 9 and 10), while for the ESTs AV381130 and AV381126 no putative functions could be predicted. The expression of Spint4, Rnase9, and AV381130 was found to be under a direct or indirect regulation by androgens, while the expression of Rnase10 is regulated by a testicular factor(s) other than androgen. None of the genes were expressed in the immature epididymis, while mRNAs were detected from d 17 onward, at the time of maturation of epididymal epithelium. However, the expression of AV381130 was not detected until d 30 after birth, indicating a close connection between gene expression and puberty.

Hydroxysteroid (17p)-dehydrogenasetype 1 (HSD17B1) catalyzes the conversion of low active 17-ketosteroids, androstenedione (A-dione) and estrone (E1) to highly active 17-hydroxysteroids, testosterone...