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The aim of this study was to evaluate whether the Serum Netrin-1 and Urinary KIM-1 (Kidney Injury Molecule-1) levels are associated with the detection of preeclampsia. A total of 90 patients, including 36 normal pregnant women, 29 patients with nonsevere preeclampsia and 25 patients with severe preeclampsia, were included in this study. Maternal serum Netrin-1 and Urinary KIM-1 levels were measured by using an enzyme-linked immunosorbent assay (ELISA). The results showed that the Levels of Netrin-1 and KIM-1 were statistically higher in women with preeclampsia as compared with normal pregnant women. Furthermore, the Netrin-1 level in women with severe preeclampsia was significantly higher than nonsevere preeclamptic women. inconclusion the current study showed that Maternal serum level of Netrin-1 and Urinary level of KIM-1 can be used as early biomarkers for the detection of preeclampsia.IMPACT STATEMENTWhat is already known on this subject? Preeclampsia is a disorder of widespread vascular endothelial malfunction and vasospasm that occurs after 20 weeks' gestation. Netrin-1 was found to promote angiogenesis. Alteration of placental angiogenesis in early pregnancy is a well-known reason for placental dysfunction such as preeclampsia. Kidney injury with proteinuria is a characteristic feature of preeclampsia. Urine KIM-1 is the most potential biomarker for renal injury in preeclampsia. Due to these facts, we aimed to investigate the role of maternal serum Netrin-1 and Urine KIM-1 levels in preeclampsia presence and severity.What the results of this study add? A significant relationship between Netrin-1 and KIM-1 levels with preeclampsia.What the implications are of these findings for clinical practice and/or further research? Based on these findings, we concluded that increased levels of Netrin-1 and KIM-1 are associated with severe preeclampsia.

The imbalance of Th17/Treg cells has been recently suggested as a new risk factors for recurrent implantation failure (RIF). Furthermore Th17/Treg cells are involved in immune regulation in peripheral blood and endometrial tissue of patients with RIF. In this research, we investigated the effects of Hydroxychloroquine (HCQ) on the level and function of Th17 and Treg cells in women with RIF. It may be possible to improve pregnancy outcomes by modulating high cytokine levels.Women with RIF received oral HCQ (Our results demonstrated that the administration of HCQ in RIF women with immune cell disorders during pregnancy could affect the Th17/Treg ratio and enhance Treg and diminish Th17 responses which may be associated with successful pregnancy outcomes. However, significant difference in pregnancy outcomes was not observed in the present study.

Background Low maternal vitamin D status has been associated with several adverse outcomes during pregnancy. The aim of the study was to evaluate the vitamin D levels in preeclamptic and healthy pregnant women and the role of vitamin D deficiency in the etiology of preeclampsia. Methods In this case-control study, 80 preeclamptic women and 80 healthy pregnant women were selected from Motahari hospital in Urmia, Iran. 2 ml of venous blood sample was collected from each pregnant woman and the serum 25-OH-D level was measured by Enzyme-Linked Immunosorbent Assay (ELISA) and reported in nanograms per milliliter. levels of 25-OH-D less than 10 ng mL−1, between 10 ng mL−1 and 29 ng mL−1 and more than 30 ng mL−1, were considered as deficient, insufficient and normal 25-OH-D concentrations, respectively. Results were analyzed by independent t-test, Mann-Whitney U test, and logistic regression. Results Preeclamptic women (n = 80) were noted to have decreased total 25-OH-D levels relative to healthy control women (n = 80; P = 0.01). This difference in total 25-OH-D remained significant after control for potential confounders [odds ratio (OR) = 4.79, confidence interval (CI) = 1.45–9.87, P = 0.01]. Conclusion These results showed that vitamin D deficiency has a statistically significant relationship with preeclampsia and support the hypothesis that vitamin D deficiency may be a risk factor for preeclampsia.

Cellular immune abnormalities such as the imbalance between T-helper (Th) 1 and Th2 cytokines have been implicated as potentially modifiable causes of idiopathic repeated implantation failures (RIF). The purpose of this study was to investigate the effects of hydroxychloroquine on IL-10 and TNF-α secretion, expression of T-bet and GATA-3 transcription factors and cellular localization of TNF-α, IFN-γ, IL-10 and IL-4 in endometrial cells in women with RIF.A total of 17 women with a history of RIF and elevated TNFα/IL-10 ratio (TNFα/IL-10 = 30.6) were included in the study. The serum levels of TNFα and IL-10, the expression of transcription factors related to Th1 and Th2 cells and the immune-reactivity of TNFα, IFN-γ as Th1 related cytokines and IL-10, IL-4 as Th2 related cytokines in endometrial tissues were evaluated by ELISA, real-time PCR, and fluorescent immunohistochemistry respectively. All, evaluations were done both before and after treatment with hydroxychloroquine (400 mg/orally per day).Hydroxychloroquine treatment significantly decreased (p 0.0001) serum level of TNF-α and significantly increased serum level of IL-10 (p 0.0001). T-bet, the Th1 transcription factor, expression was down-regulated and GATA-3, the Th2 transcription factor, expression was up-regulated. IL-10 and IL-4 fluorescent immunoreactivities significantly increased (p 0.05 and p 0.001 respectively) and TNFα and IFN-γ fluorescent immunoreactivities significantly decreased (p 0.05) in endometrial tissue in women with RIF after treatment in comparison with before treatment.Hydroxychloroquine administration in women with RIF With a high TNF-α/IL-10 ratio during the implantation window can decrease this ratio and seems to be an effective therapeutic strategy in RIF caused by cellular immune abnormalities through a shift in Th2 responses.

The aim of this study was to investigate the effects of rapamycin (rapa) and metformin (met), combined administration on testicular torsion-detorsion (T/D) injury. A total of 108 male rats were divided randomly into six groups (n = 18), control, sham-operated, T/D, T/D + met (100 mg/kg), T/D + rapa (0.25 mg/kg) and T/D + met (100 mg/kg)+rapa (0.25 mg/kg). Except for the control and sham groups, torsion was created by rotating the right testis 720° in a clockwise direction for 1 h. Treatment groups received drug intraperitoneally, 30 min before detorsion. The right testis of 6 animals from each group was excised 4 h after detorsion for the measurement of lipid peroxidation, caspase-3, and antioxidant enzyme activities. Histopathological changes and germ cell apoptosis were determined by measuring mean of seminiferous tubules diameters (MSTD) and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate–biotin nick end labeling (TUNEL) test in rest of animals, 24 h after detorsion. In T/D group tissue malondialdehyde (MDA) level and caspase-3 activity increased and the activities of catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx) decreased in comparison with the control group after detorsion. Met and rapa separately pre-treatment reduced MDA and caspase-3 levels, normalized antioxidant enzyme activities, reduced germ cell apoptosis and improved the MSTD in comparison with T/D group. However combined administration of met and rapa indicated a significant augmented effect as compared to the individual drug interventions on the reversal of T/D induced oxidative stress, apoptosis, and histologic changes, suggesting a synergistic response. Thus, this study shows that rapa and met combination have significant synergistic effects against oxidative stress and apoptosis and opens up further possibilities for the design of new combinatorial therapies to prevent tissue damage after ischemia-reperfusion (I/R).

Diabetes mellitus (DM) is a glucose, fat, and protein metabolism disorder. Testicular toxicity and reproductive dysfunction are consequences of streptozotocin (STZ)-induced diabetes. Oxidative stress has been suggested as one of the main mechanism involved in STZ-induced toxicity. Since many studies revealed that Silymarin (SMN), a plant extract, has anti-diabetic and antioxidant activity, this study was conducted to evaluate the effects of this natural agent on testicular function and male reproductive parameters in STZ-induced diabetic rats. Sperm parameters, in vivo reproductive performance, and oxidative stress markers were measured. In addition, relative expression of apoptotic-related genes and testosterone level were evaluated. STZ-induced diabetes altered sperm parameters, reduced reproductive performances, increased lipid peroxidation (LPO), and decreased antioxidant enzyme activities. Our results showed that SMN intake improved sperm parameters, reproductive performances, decreased LPO, and increased antioxidant enzyme activities. The relative mRNA expression of Bcl-2 was significantly reduced, and that of Bax, Caspase-3 was significantly increased in the diabetic rats compared to the control group. SMN significantly increased the expression of Bcl-2 and decreased the expression of Bax, Caspase-3. Serum levels of testosterone showed a significant decreased in diabetic rats, compared to the control group and serum testosterone levels revealed a significant increase in groups that received SMN. The protective potential of SMN against oxidative stress in STZ-induced testicular toxicity and its potential to improve fertility in diabetic rats makes it a potential candidate to reverse the toxic effect of diabetes on the testis by herbal antioxidants.

The study was designed to evaluate the effects of metformin on apoptosis and epididymal sperm quality in a rat testicular ischaemia/reperfusion (I/R) injury model. A total of 72 male rats were divided into four groups (n = 18 for each group): group 1 (sham-operated group), group 2 (metformin group), group 3 (torsion/detorsion [T/D] + saline) and group 4 (T/D + 300 mg kg-1 metformin). Testicular torsion was achieved by rotating the right testis 720° in a clockwise direction for 1 hr. Tissue malondialdehyde (MDA) level and caspase-3 activity increased and the activities of catalase, superoxide dismutase and glutathione peroxidase decreased in comparison with sham-operated group 4 hr after detorsion (p < .001). In six rats of each group 24 hr after detorsion, histopathological changes and germ cell apoptosis were significantly deteriorated by measuring mean of seminiferous tubule diameters (MSTD) and TUNEL test. Moreover, 30 days after T/D, sperm concentration and motility were examined in six animals per group. Metformin pre-treatment reduced MDA and caspase-3 levels and normalised antioxidant enzyme activities 4 hr after detorsion, and germ cell apoptosis was significantly decreased, and the MSTD, as well as sperm functions, was significantly improved. Reduction in oxidative stress and apoptosis may have a major role in cytoprotective effects of metformin.