PTSD is associated with disturbed hepatic morphology and metabolism. Neuronal mitochondrial dysfunction is considered a subcellular determinant of PTSD, but a link between hepatic mitochondrial dysfunction and hepatic damage in PTSD has not been demonstrated. Thus, the effects of experimental PTSD on the livers of high anxiety (HA) and low anxiety (LA) rats were compared, and mitochondrial determinants underlying the difference in their hepatic damage were investigated. Rats were exposed to predator stress for 10 days. Then, 14 days post-stress, the rats were evaluated with an elevated plus maze and assigned to HA and LA groups according to their anxiety index. Experimental PTSD caused dystrophic changes in hepatocytes of HA rats and hepatocellular damage evident by increased plasma ALT and AST activities. Mitochondrial dysfunction was evident as a predominance of small-size mitochondria in HA rats, which was positively correlated with anxiety index, activities of plasma transaminases, hepatic lipids, and negatively correlated with hepatic glycogen. In contrast, LA rats had a predominance of medium-sized mitochondria. Thus, we show links between mitochondrial dysfunction, hepatic damage, and heightened anxiety in PTSD rats. These results will provide a foundation for future research on the role of hepatic dysfunction in PTSD pathogenesis.

Stress-induced conditions are associated with impaired cerebral blood flow (CBF) and increased risk of dementia and stroke. However, these conditions do not develop in resilient humans and animals. Here the effects of predator stress (PS, cat urine scent, ten days) on CBF and mechanisms of CBF regulation were compared in PS-susceptible (PSs) and PS-resilient (PSr) rats. Fourteen days post-stress, the rats were segregated into PSs and PSr groups based on a behavior-related anxiety index (AI). CBF and its endothelium-dependent changes were measured in the parietal cortex by laser Doppler flowmetry. The major findings are: (1) PS susceptibility was associated with reduced basal CBF and endothelial dysfunction. In PSr rats, the basal CBF was higher, and endothelial dysfunction was attenuated. (2) CBF was inversely correlated with the AI of PS-exposed rats. (3) Endothelial dysfunction was associated with a decrease in eNOS mRNA in PSs rats compared to the PSr and control rats. (4) Brain dopamine was reduced in PSs rats and increased in PSr rats. (5) Plasma corticosterone of PSs was reduced compared to PSr and control rats. (6) A hypercoagulation state was present in PSs rats but not in PSr rats. Thus, potential stress resilience mechanisms that are protective for CBF were identified.

We have suggested that adipocytes in uterine scars may affect the development of the placenta accrete spectrum (PAS). In the experimental part, we explored adipocytes in the uterine wall by the twelfth sexual cycle after surgery. In the clinical part, we investigated adipocyte clusters in the cesarean scar of pregnant women with and without PAS. The uterine wall was evaluated in gross and histological sections using morphometry, histochemistry (hematoxylin and eosin stain, Mallory stain), and immunohistochemistry for FABP4 (adipocyte markers), CD68, CD163, CD206 (macrophages), CD 34 (endothelium), cytokeratin 8 (epithelium), aSMA (smooth muscle cells). The design included an experimental study on Sprague–Dawley rats (n = 18) after a full-thickness surgical incision on the seventh (n = 6), 30th (n = 6), and 60th day (n = 6). The clinical groups include pregnant women without uterine scars (n = 10), pregnant women with a uterine scar after previous cesarean sections (n = 10), and women with PAS (n = 11). Statistical processing was carried out using nonparametric methods. Comparisons were conducted using the Mann–Whitney U-test and Kruskal–Wallis test. Statistical significance was considered at p < 0.05. On the seventh day, the rat uterine horn was enveloped by adipose tissue, which contained crown-like structures with FABP4+, CD68+, CD206+, and CD163+ cells. FABP4+ cells in the uterine wall were absent by the 30th day. The number of CD206+ and CD163+ cells in the adipose tissue decreased by the 30th day. On the 60th day, the attachment of fat tissue was revealed in the form of single strands. The serous layer around the damaged area totally recovered on the 60th day. FABP4+ cells were not detected in the uterine wall samples from pregnant women without a previous cesarean section. Adipocytes were found in the scar during non-complicated pregnancy and with PAS. Reducing the number of CD68+ cells in adipocyte clusters, there were in myometrium with PAS. Increased CD206+ and CD163+ cells were revealed in uterine adipocyte clusters of the group. According to the experimental finding, adipocytes should be absent in the uterine wall by the 12th sexual cycle after a full-thickness surgical incision. The presence of adipocyte clusters in cesarean scar indicated the disturbance of cell interaction. Differences in the numbers of CD206 and CD163 cells in adipocyte clusters between groups with and without PAS may be indirect evidence that uterine adipocytes affect the development of PAS.

Introduction. Data about the role of components of adipose tissue in the repair of damaged uterine walls are limited, although a number of authors claim that cell-based drugs from adipose tissue have a positive effect on the repair of damaged uterine walls in laboratory rodents. Meanwhile, stem cells derived from adipose tissue are considered to be the most promising type of cells in regenerative medicine. The aim of the studywas to evaluate the adipocyte components in the uterine wall of rats in healing after a full-thickness surgi-cal incision. Materials and methods. We conducted the study on 40 female Sprague Dawley rats. The animals were sub-jected to a full-thickness longitudinal incision in the wall of the right uterine horn, with the left one serving as an intact control. We carried out morphological examinations of the uterine walls daily in 5 animals from day 1 to 7 and on day 15. The sections from paraffin blocks were stained with hematoxylin and eosin and Mallory’s trichrome staining. Immunohistochemistry detected FABP4+ adipocytes and CD68+ macrophages. The morphometric study was carried out using the Leica system (Leica, Germany). The results underwent processing in the Statistica 12 software (StatSoft). Results. We noticed the period of the most active interaction of adipose tissue with the damaged horn to last from day 3 to 15 and coincide with the macrophage activation in the healing zone. The intact left uterine horn was not involved in the interaction processes with the mesenteric adipose tissue. Starting from day 3 FABP4+ cells in the uterine wall of the operated horn formed groups, creating rounded nest-like structures. Clusters of FABP4+ cells were localized in the healing zone, near the suture material, and in the perime-trium near the mesentery attachment sites. The changes over time of the indicators of the area of cell nests depended on the localization and duration of healing. There were no FABP4+ cells in the left intact horn. Conclusion. We characterized the morphological interaction of adipose tissue with the damaged uterine wall during the first two weeks after a full-thickness surgical incision of the rat uterine horn. The results of the study indicate that adipocytes take an active part in the healing after a surgical incision of the rat uterine wall at the earliest stages. Keywords: rat uterus, hysterotomy, healing, adipocytes, macrophages

(1) Background: The components of the fibrinolytic system and its main component, plasminogen, play a key role in the first months of pregnancy. The effect of autoantibodies interacting with plasminogen in the formation of retrochorial hematoma is unknown. The aim of our study was to determine the role of plasminogen and IgA, IgM, and IgG, which bind to plasminogen, in retrochorial hematoma. (2) Methods: Prothrombin time (PT), thrombin time (TT), partial activated thromboplastin time (aPTT), soluble fibrin-monomer complex (SFMC), D-dimer, plasminogen activity (%Plg), plasminogen concentration (Plg), and the levels of IgG (IgG-Plg), IgM (IgM-Plg), IgA (IgA-Plg) interacting with plasminogen were determined in plasma samples of 57 women with normal pregnancy and 16 with retrochorial hematoma. (3) Results: %Plg in plasma samples from women with retrochorial hematoma was significantly lower than in plasma samples from women with normal pregnancy. The diagnostic significance of %Plg in the ROC analysis was AUC = 0.85. A direct correlation was found between aPTT and the level of autologous IgM interacting with plasminogen. (4) Conclusions: A decrease in the activity of plasminogen in the blood serum of women in the first trimester of pregnancy may indicate disturbances in the hemostasis system and the formation of retrochorial hematoma. According to the results of the study, it is possible to recommend the determination of plasminogen activity in the management of pregnant women in gynecological practice.

Introduction. One of the most challenging problems faced in gynecology is Asherman’s syndrome (AS), characterized by the formation of intrauterine adhesions, partial or complete obliteration of the uterine cavity with scar tissue, and the loss of the functional layer of the endometrium following intrauterine interventions. Treatments for AS are not always effective. This indicates a need to search and evaluate the effectiveness of new approaches to the prevention of fibrosis and stimulation of endometrial regeneration. According to ethical principles, this is possible only when simulating AS on laboratory animals. The aim of the work is to develop an etiologically adequate model of AS in Sprague Dawley rats. Materials and methods. We simulated AS in 18 female Sprague Dawley rats that were divided into 3 groups (6 rats in each). Operations were performed in the estrus phase. We made longitudinal incision of the right uterine horns, and the endometrium was scraped out to the inner layer of the myometrium with the scalpel. Groups 1 and 2 underwent only endometrial scraping. In group 3 abdominal cavities were opened on day 7 after curettage and intrauterine adhesions were destroyed with a needle inserted into the horn. Then, the standard procedure for suturing surgical wound was performed. The animals were removed from the experiment on days 7 (group 1) and 15 (groups 2 and 3) after the surgery with an overdose of ether anesthesia. The tissue samples of the operated and non-operated uterine horns were fixed with 10% buffered formalin and embedded in paraffin; the sections were stained with hematoxylin and eosin. Results. Macroscopic examination on day 7 after the surgery showed that all females had a compaction and contraction of the operated area of the uterine horn and uterine cavity fluid. On day 15, fluid collection was more pronounced. After the destruction of the uterine adhesions in rats from group 3, there was no fluid collection or it was less voluminous than in females of other groups. Histological examination showed that on days 7 and 15 after endometrial curettage, the uterine cavity and the luminal epithelium covering it were absent due to complete replacement by connective tissue. Uterine glands were not detected or were individual. On day 7 after the destruction of the adhesions and on day 15 after endometrial scraping the subjects developed a small stenosed uterine cavity lined with luminal epithelium or a larger uterine cavity containing single or multiple adhesions covered with epithelium. The number of glands was significantly smaller than in the non-operated horn. Conclusion. To simulate Asherman’s syndrome, female Sprague Dawley rats in the estrus phase were scraped out of the endometrial layer of the right uterine horn. On days 7 and 15 after surgery, the uterine cavity and luminal epithelium were absent due to complete replacement with connective tissue, which proves the formation of intrauterine adhesions and the adequacy of the obtained model. A significant difference of the original model was the destruction of the adhesions on day 7 after endometrial damage to remove excess fluid in the uterine cavity and restore uterine patency, which led to the formation of the uterine cavity and re-epithelialization on day 15. The developed model of Asherman’s syndrome can be used to develop new approaches to the prevention of adhesive process and the restoration of endometrial structure and functionality. Keywords: Asherman’s syndrome, experimental model, rat uterus, endometrial curettage, intrauterine adhesions