There is evidence that the mass and metabolic status of the adipose tissue that produces adipokines significantly affect the activity of the hypothalamic-pituitary-gonadal (HPG) axis and the synthesis of testosterone. This is due to the fact that adipokines, such as leptin, adiponectin, visfatin and resistin have an important role in the regulation of the male HPG axis and steroidogenesis in the testes. The regulation of the HPG axis by adipokines can be carried out both through the changes the plasma levels of adipokines (a systemic regulation) and through the changes in the expression and activity of adipokines in the pituitary and testes, the components of the HPG axis (an autonomous regulation). This review presents the comprehensive analysis of the involvement of leptin, adiponectin, resistin and visfatin in the regulation of the male HPG axis and the testosterone production, as well as of the possible mechanisms of this regulation. The role of adipokines in the dysregulation of the male reproductive system and the impaired steroidogenic activity in the testes in obesity and type 2 diabetes mellitus are also discussed.

Drug delivery systems enhance drug efficacy while minimizing side effects. Liposomes, as well-studied and clinically approved carriers, offer biodegradability, biocompatibility, and low toxicity, making them suitable for delivering various pharmacological agents. Granulocyte colony-stimulating factor (G-CSF), a key growth factor, has shown therapeutic potential, particularly in infertility treatment. It effectively manages chronic and refractory endometritis by improving endometrial receptivity and increasing embryo implantation success. Studies indicate that G-CSF promotes endometrial growth and enhances the uterine microenvironment, benefiting patients with recurrent implantation failures and chronic endometritis. Encapsulation of G-CSF in liposomes enhances its stability, bioavailability, and controlled release. G-CSF-loaded liposomes were prepared using passive loading via the thin-film hydration method. The size of the liposomes, polydispersity index (PDI), and zeta potential were determined using dynamic and electrophoretic light scattering methods, and the encapsulation efficiency was measured using high-performance liquid chromatography. The morphology of the liposomes was established and confirmed using cryogenic transmission electron microscopy. The cytocompatibility of the G-CSF-loaded liposomes was evaluated on human dermal fibroblasts using an MTT assay. The G-CSF-loaded liposomes had an average particle size of 161.9 ± 9.9 nm, a PDI of 0.261 ± 0.03, and a zeta potential of +2.09 ± 0.10 mV, exhibiting high physical stability during long-term storage at +4 °C and 60% humidity. The passive loading method resulted in a 52.37 ± 3.64% encapsulation efficiency of the active substance. The analysis of cell viability revealed no cytotoxicity toward liposomes loaded with G-CSF and demonstrated a dose-dependent effect on the viability of human dermal fibroblasts. Thus, the obtained data confirm the successful preparation of G-CSF-loaded liposomes. However, to fully understand their effectiveness in biomedical applications, further research is needed, including an evaluation of their effectiveness in vivo. Such studies will help in determining the potential of these formulations for specific biomedical purposes and evaluating their safety and efficacy in living systems.

Adipokines are involved in the regulation of the female reproductive system. The purpose was to study the possibility of using adipokines levels in the follicular fluid to predict IVF efficiency.Fo...

BACKGROUND: Cell therapy is a promising trend in treating characterized by inflammation and sclerosis diseases such as genital tuberculosis, marked by pelvic inflammatory disease and uterine tube occlusion. AIM: Efficacy evaluation of combined mesenchymal stem cells and specific polychemotherapy treatment of the experimental genital tuberculosis. MATERIALS AND METHODS: Chinchilla rabbits (n = 27) were divided on 4 groups. Group 1 (n = 6) comprised control group, healthy animals. Group 2 (n = 7) infected with genital tuberculosis, without treatment. Group 3 (n = 7) infected with genital tuberculosis, treated with anti-tuberculous drugs only. Group 4 (n = 7) infected with genital tuberculosis, treated with anti-tuberculous drugs and mesenchymal stem cells. Culture of M. tuberculosis Erdman in dose 107 CFU/0.2 ml was injected under the left uterine tube serosa for the genital tuberculosis modelling. For treatment efficacy evaluation following tests were used: full blood count, blood chemistry, hysterosalpingography, diagnostic laparoscopy, peritoneal macrophage phagocytic activity assessment. RESULTS: Infected with genital tuberculosis animals had leukocytosis, elevated C-reactive protein, swelled and occluded uterine tubes. Treated with anti-tuberculous drugs and mesenchymal stem cells rabbits had lower white blood cell count (8.18 1.39 109/L vs 9.32 1.36 109/L, р 0.05) and C-reactive protein (1.1 0.8 mg/L vs 2.2 1.2 mg/L, р 0.01) compared to animal treated with anti-tuberculous drugs only. Animals in group 4 had also increased peritoneal macrophage phagocytic activity. Treated with mesenchymal stem cells animals had unobstructed uterine tubes, stabilized adhesive process within small pelvis with reparative process prevalence. CONCLUSIONS: Mesenchymal stem cells combined with anti-tuberculous drugs therapy favors reparative process in uterine tubes in genital tuberculosis.

The effectiveness of the use of a modified intrauterine gel form of granulocyte colony stimulating factor in the complex treatment of Ascherman syndrome is evaluated. The study involved 31 patients with a history of Ascherman syndrome. For 6 months, the patients underwent weekly intrauterine administration of 1 ml of gel with a concentration of granulocyte colony stimulating factor of 9 million IU/ml using an intrauterine catheter. Monthly M-echo was evaluated on the 19th–22nd day of the menstrual cycle, as well as the volume of menstrual blood loss according to the Pictorial Blood Loss Assessment Chart. After the treatment was completed, a control hysteroscopy was performed. There is a statistically significant increase in M-echo from 2. 61 ± 1. 71 to 6. 52 ± 1. 23 mm (p < 0. 001). At the same time, the proportion of patients with M-echo 6 and 7 mm increased from 6. 45 and 0% to 80. 65 and 51. 61, respectively, over the 6 months of the study. There is also a statistically significant increase in menstrual blood loss from 24. 9 ± 2. 6 to 53. 5 ± 3. 4 points on the Pictorial Blood Loss Assessment Chart (p < 0. 001). A response to therapy was achieved in 17 patients, among them 12 patients were diagnosed with pregnancy that occurred spontaneously (17. 65%) or as a result of in vitro fertilization protocol (52. 9%). The data obtained indicate that intrauterine administration of a gel with granulocyte colony stimulating factor promotes endometrial regeneration in patients suffering from Ascherman syndrome, which is expressed in an increase in M-echo and the volume of menstrual blood loss. Thus, adjuvant use of a hydrogel with granulocyte colony stimulating factor and hyaluronic acid is an effective treatment option in restoring reproductive function and preventing recurrence of adhesiogenesis after surgical treatment of Ascherman syndrome. In general, the proposed gel form with granulocyte colony stimulating factor allows us to reduce the frequency of administration of the drug, which theoretically can increase both the compliance of patients primarily by reducing the number of invasive procedures, and reduce treatment costs.

The analysis of the cause of repeated implantation failures is currently at the stage of accumulation of scientific knowledge. Immunomodulation of the endometrium after intrauterine insemination with activated autologous peripheral blood mononuclear cells may be a promising therapeutic solution. Objective of the study. To determine the local cytokine profile of the endometrium in patients with multiple unsuccessful attempts at assisted reproductive technologies (ART) and the effectiveness of its correction with a lyophilisate solution of peripheral blood mononuclear cell secretome by intrauterine perfusion. Material and methods. The study included 55 patients aged 29 to 47 years with a history of infertility for more than 5 years and multiple ART failures. The patients were divided into 2 groups. The main group consisted of women who became pregnant, the comparison group consisted of women who did not become pregnant as a result of treatment. After treatment, 14 patients underwent repeated analysis of the local cytokine profile of the endometrium. The study of the endometrial microbiota and the determination of genes of markers of the local immune response were carried out using molecular biological tests. Results. When analyzing the ratios of innate immunity gene expression, statistically significant differences were found between the IL-18 indicators and the IL-10/IL-18 profile. The IL-18 level after treatment became significantly higher compared to the indicator before treatment, which was 3.8 [3.47; 4.07] and 3.3 [2.747; 3.5], respectively, p< 0.05. The IL-10/IL-18 ratio before treatment was 26.45 [21.64; 160.54], which was higher compared to the indicator after treatment — 16.7 [10.45; 50.77], p< 0.05. Conclusions. After complex therapy with lyophilisate of peripheral blood mononuclear cell secretome (Superlymph), improvement of immunological parameters of the endometrium was achieved, increasing the probability of successful implantation. Intrauterine administration of peripheral blood mononuclear cell secretome has potentially shown itself as a good way to modulate endometrial receptivity.