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.
Study question Can the adipokines levels and ratios in the follicular fluid (FF) be used to predict in vitro fertilization (IVF) outcomes? Summary answer The leptin level and ratios leptin/ghrelin and leptin/adiponectin in FF are reliable prognostic factors for IVF outcomes in women with normal body mass index (BMI). What is known already The adipose tissue serves not a simple fat storage, rather an important endocrine organ, producing adipokines, such as leptin, adiponectin, ghrelin and others. Adipokines have been shown to regulate the cardiovascular system, food intake, metabolism, inflammation, metastatic spread of tumors,and also reproduction, affecting the activity of the hypothalamo-pituitary-gonadal axis. The plasma and FF adipokines have been used as prognostic factors for IVF outcomes, but the obtained results are controversial. The most promising in this case may be the distribution of patients into groups in accordance with their BMI and a separate study of adipokine ratios in them. Study design, size, duration Women (n = 53), who undergo IVF, were divided on two groups, according to their BMI: normal BMI (18.5–24.9 kg/m2, n = 25) and increased BMI (>25.0 kg/m2, n = 28). Depending on IVF outcomes after the antagonist protocol, the groups formed were subsequently subdivided into two groups each: non-pregnant with normal BMI (nPN, n = 16), pregnant with normal BMI (PN, n = 9), non-pregnant with increased BMI (nPI, n = 21), pregnant with increased BMI (PI, n = 7). Participants/materials, setting, methods: Inclusion criteria for participants were: age 18–45 years and infertility due to male/tubal factor. Exclusion criteria were: polycystic ovarian syndrome (PCOS), diabetes mellitus, or plasma level of anti-Müllerian hormone <1.0 ng/mL. The FF from the first punctated follicle was collected and tested for leptin, adiponectin and ghrelin levels using ELISA kits. If gestational sac was seen in uterine cavity using ultrasound on day 21–25 after embryo transfer, pregnancy was diagnosed. Main results and the role of chance Women with increased BMI had, as a rule, higher FF levels of leptin and the leptin/ghrelin and leptin/adiponectin ratios, compared with women with normal BMI. Furthermore, leptin level was higher in PN as compared to nPN (21.61±2.55 vs 10.54±1.16, p < 0.05), but did not differ in the PI and nPI groups. The same pattern was obtained for the leptin/ghrelin and leptin/adiponectin ratios. The ghrelin level showed an inverse pattern. It was higher in nPN as compared to PN (3.80±0.78 vs 1.39±0.19, p < 0.05), but did not differ in women with increased BMI. The obtained data demonstrate that the association between the adipokine levels in FF and the IVF outcomes is better in women with normal BMI than in women with increased BMI. Adipokines, which differed among the study groups, were evaluated as prognostic factors in women with normal BMI.The values were calculated at which pregnancy became unlikely: leptin level <15 ng/mL, leptin/ghrelin ratio <9, and leptin/adiponectin ratio <5. For each indicators, the sensitivity and specificity were >88%. The predictive power of these indicators in the clinic using the odds ratio (95% confidence interval) was: leptin level 7.11 (1.23–40.99, p < 0.05), leptin/ghrelin 29.53 (1.53–570.83, p < 0.05), and leptin/adiponectin 7.11 (1.23–40.99, p < 0.05). Limitations, reasons for caution The main limitation of the study is a relative small number of patients, although the differences between the investigated groups were significant. Furthermore, women with low ovarian reserve, age > 40 years, endometriosis or PCOS were not included in the study. Wider implications of the findings: The obtained results indicate the good prospects for using such indicators as the adipokines levels and their ratio in FF to predict IVF outcomes in women with low ovarian reserve, endometriosis and PCOS, but with normal BMI. Trial registration number Not applicable
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.
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