Estradiol-17β (E2) is a key hormone regulating reproductive functions in females. In pigs, E2, as the main conceptus signal, initiates processes resulting in prolonged corpus luteum function, embryo development, and implantation. During early pregnancy the endometrium undergoes morphological and physiological transitions that are tightly related to transcriptome changes. Recently, however, the importance of E2 as a primary conceptus signal in the pig has been questionable. Thus, the aim of the present study was to determine the effects of E2 on the porcine endometrial transcriptome in vivo and to compare these effects with transcriptome profiles on day 12 of pregnancy. Microarray analysis revealed differentially expressed genes (DEGs) in response to E2 with overrepresented functional terms related to secretive functions, extracellular vesicles, cell adhesion, proliferation and differentiation, tissue rearrangements, immune response, lipid metabolism, and many others. Numerous common DEGs and processes for the endometrium on day 12 of pregnancy and E2-treated endometrium were identified. In summary, the present study is the first evidence for the effect of E2 on transcriptome profiles in porcine endometrium in vivo in the period corresponding to the maternal recognition of pregnancy. The presented results provide a valuable resource for further targeted studies considering genes and pathways regulated by conceptus-derived estrogens and their role in pregnancy establishment.During early pregnancy in the pig, porcine conceptuses (embryos with associated membranes) secrete E2, which is regarded as the pregnancy recognition signal required for prolonged progesterone synthesis and secretion by corpora lutea (CLs). Porcine conceptuses secrete estrogens in a biphasic manner-the first increase of conceptus-derived estrogens occurs on days 11-13 after fertilization and the second is between days 15 and 25-30 after fertilization (reviewed in [2]). However, the levels of conceptus-derived estrogens in the uterine lumen may also vary depending on the number of conceptuses [1]. The period of elevated E2 synthesis and secretion by porcine conceptuses between days 11-13 of pregnancy is a process defined as the maternal recognition of pregnancy [5]. This is the critical period for establishment and development of pregnancy as the highest mortality rate of embryos in animals including pigs is observed during the peri-implantation period [6]. Embryonic estrogen synthesis and secretion not only prolongs the CL lifespan but also enhances P4-induced endometrial receptivity for implantation. Following the decrease of the progesterone receptor expression in the endometrial luminal and glandular epithelia, the expression of the estrogen receptor (ESR1) is up-regulated in these structures, which in turn is important for the cell-specific responses to conceptus estrogens released on day 12 of pregnancy [7]. Estrogen is involved in stimulation of uterine secretory activity [8], increased blood flow [9], endometrial edema [10], and the regul...

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PurposeChronic kidney disease (CKD) is an estimated risk factor for increased mortality and morbidity due to fibrinolytic system disturbances. Progressive loss of renal function leads to retention of uremic toxins. Anthranilic acid (AA) is a tryptophan-derived uremic toxin with multidirectional properties that can affect the hemostatic system. The goal of this study was to examine the association between AA and the parameters of fibrinolysis at different stages of CKD.MethodsPatients with CKD were divided into two groups: mild-to-moderate (n = 20) and severe-to-end-stage CKD (n = 28). Seventeen healthy volunteers served as an additional control group. Parameters of fibrinolysis, inflammation, and monocytes activation were determined by ELISA immune-enzymatic kits. AA levels were evaluated using high-performance liquid chromatography.ResultsAA concentration and parameters of fibrinolysis: urokinase-type plasminogen activator (uPA), its soluble receptor (suPAR), tissue plasminogen activator (tPA), tissue plasminogen activator inhibitor-1 (PAI-1) and plasmin-antiplasmin complex (PAP) were significantly elevated in the CKD groups compared with the controls. The markers of inflammation, monocyte activation, and impaired kidney function were also increased in those with CKD. AA was positively correlated with the uPA/suPAR system in the early stages of CKD, whereas during severe-to-end-stage CKD, inverse relationships were observed between AA, tPA and PAI-1. Additionally, AA was an independent variable associated with tPA in patients with CKD overall and with uPA levels in the mild-to-moderate CKD group.ConclusionsObtained results suggest for the first time the association between AA and the fibrinolytic system in CKD patients. The distinct relationship between AA and individual parameters of fibrinolysis appears to be dependent on CKD stage.