Mesenchymal Stem-Cell Derived Exosome Therapy as a Potential Future Approach for Treatment of Male Infertility Caused by Chlamydia Infection.

Some microbial sexually transmitted infections (STIs) have adverse effects on the reproductive tract, sperm function, and male fertility. Given that STIs are often asymptomatic and cause major complications such as urogenital inflammation, fibrosis, and scarring, optimal treatments should be performed to prevent the noxious effect of STIs on male fertility. Among STIs, Chlamydia trachomatis is the most common asymptomatic preventable bacterial STI. C. trachomatis can affect both sperm and the male reproductive tract. Recently, mesenchymal stem cells (MSCs) derived exosomes have been considered as a new therapeutic medicine due to their immunomodulatory, anti-inflammatory, anti-oxidant, and regenerative effects without consequences through the stem cell transplantation based therapies. Inflammation of the genital tract and sperm dysfunction are the consequences of the microbial infections, especially Chlamydia trachomatis. Exosome therapy as a noninvasive approach has shown promising results on the ability to regenerate the damaged sperm and treating asthenozoospermia. Recent experimental methods may be helpful in the novel treatments of male infertility. Thus, it is demonstrated that exosomes play an important role in preventing the consequences of infection, and thereby preventing inflammation, reducing cell damage, inhibiting fibrogenesis, and reducing scar formation. This review aimed to overview the studies about the potential therapeutic roles of MSCs-derived exosomes on sperm abnormalities and male infertility caused by STIs.

Potential of Mesenchymal Stem Cell-Derived Exosomes as a Novel Treatment for Female Infertility Caused by Bacterial Infections.

Neisseria gonorrhoeae and Chlamydia trachomatis are the most common causes of bacterial sexually transmitted diseases (STDs) with complications in women, including pelvic inflammatory disease (PID), ectopic pregnancy, and infertility. The main concern with these infections is that 70% of infected women are asymptomatic and these infections ascend to the upper female reproductive tract (FRT). Primary infection in epithelial cells creates a cascade of events that leads to secretion of pro-inflammatory cytokines that stimulate innate immunity. Production of various cytokines is damaging to mucosal barriers, and tissue destruction leads to ciliated epithelial destruction that is associated with tubal scarring and ultimately provides the conditions for infertility. Mesenchymal stem cells (MSCs) are known as tissue specific stem cells with limited self-renewal capacity and the ability to repair damaged tissues in a variety of pathological conditions due to their multipotential differentiation capacity. Moreover, MSCs secrete exosomes that contain bioactive factors such as proteins, lipids, chemokines, enzymes, cytokines, and immunomodulatory factors which have therapeutic properties to enhance recovery activity and modulate immune responses. Experimental studies have shown that local and systemic treatment of MSC-derived exosomes (MSC-Exos) suppresses the destructive immune response due to the delivery of immunomodulatory proteins. Interestingly, some recent data have indicated that MSC-Exos display strong antimicrobial effects, by the secretion of antimicrobial peptides and proteins (AMPs), and increase bacterial clearance by enhancing the phagocytic activity of host immune cells. Considering MSC-Exos can secrete different bioactive factors that can modulate the immune system and prevent infection, exosome therapy is considered as a new therapeutic method in the treatment of inflammatory and microbial diseases. Here we intend to review the possible application of MSC-Exos in female reproductive system bacterial diseases.

Serum Levels of Angiopoietin-Like Protein 2 and Obestatin in Iranian Women with Polycystic Ovary Syndrome and Normal Body Mass Index.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a common endocrine disease in women of reproduction age and a major cause of anovulatory infertility. Insulin resistance plays an important role in the development and durability of this disorder. ANGPTL2 is known as an inflammatory mediator derived from adipose tissue that links obesity to systemic insulin resistance, and obestatin has been identified as a hormone associated with insulin resistance that suppresses food reabsorption, inhibits gastric emptying and decreases weight gain. The aim of this study was to evaluate serum levels of ANGPTL2 and obestatin in PCOS women with normal body mass index (BMI). METHODS: In this case-control study, 26 PCOS women based on the Rotterdam 2003 diagnostic criteria as the case group and 26 women with normal menstrual cycles as the control group were enrolled. Serum levels of ANGPTL2, obestatin, insulin and other hormone factors related with PCOS were measured by ELISA method and biochemical parameters were measured by an autoanalyzer. Data were analyzed by independent samples-T test, Chi Square, Correlation and a single sample Kolmogrov⁻Smirnov test using SPSS software, version 16. RESULTS: There were no significant variations in the amount of ANGPTL2, obestatin, cholesterol, low-density lipoprotein-cholesterol, high-density lipoprotein, cholesterol, creatinine and dehydroepiandrosterone-sulfate between the two groups. There were significant increases in serum levels of fasting blood sugar (p = 0.01), insulin (p = 0.04), homeostasis model assessments of insulin resistance (p = 0.04), testosterone (p = 0.02), luteinizing hormone (p = 0.004), luteinizing hormone/follicle stimulating hormone (p = 0.006) and prolactin (p = 0.04) in case group compared to the control group. A significant positive correlation was observed between ANGPTL2 and insulin (p = 0.02), HOMA-IR (p = 0.01) and, on the other hand, a significant negative correlation was observed between obestatin and insulin (p = 0.01), HOMA-IR (p = 0.008) in PCOS group. CONCLUSIONS: In this study, no significant variations were observed in serum levels of ANGPTL2 and obestatin in PCOS women with normal BMI.

CXC Ligand 5 cytokine serum level in women with polycystic ovary syndrome and normal body mass index: A case-control study.

BACKGROUND: Polycystic ovary syndrome (PCOS) is the most common endocrine disease and associated with insulin resistance. CXC Ligand 5 (CXCL5) is a new cytokine which is secreted from white adipose tissue during obesity and by blocking insulin signaling pathway inhibits the activity of insulin and promotes insulin resistance. OBJECTIVE: The aim of this study was to assess serum level of CXCL5 in PCOS women with normal body mass index. MATERIALS AND METHODS: In this case-control study, 30 PCOS women with normal body mass index as the case group and 30 non-PCOS women as the controls were enrolled. Serum levels of CXCL5, insulin and other hormones factors related with PCOS were measured by ELISA method, also the biochemical parameters were measured by autoanalyzer. RESULTS: Significant increases in serum insulin concentration, homeostasis model assessments of insulin resistance, luteinizing hormone, luteinizing hormone/follicle-stimulating hormone, fasting blood sugar, testosterone, and prolactin were observed in the case group compared to the controls. were in the serum level of CXCL5, cholesterol, low-density lipoprotein-cholesterol, high-density lipoprotein-cholesterol,dehydroepiandrosterone-sulfate, creatinine, and homeostasis model assessment of beta cell function between these two groups. CONCLUSION: In this study, no significant change was observed in serum concentrations of CXCL5 in PCOS women with normal BMI.

Oral administration of the aqueous extract of Rosmarinus officinalis in rats before renal reperfusion injury.

INTRODUCTION: Reperfusion injury leads to damage to the hemodynamic and functional parameters of the kidney. This study investigated the effects of oral administration of the aqueous extract of rosemary on improvement of changes induced by ischemia-reperfusion in rats. MATERIALS AND METHODS: Fourty male Sprague-Dawley rats were divided into 4 groups. One group was the control, rates in another group underwent sham operation, and 2 groups were exposed to reperfusion injury. Rats in one of the reperfusion groups was treated with 8% oral aqueous extract of rosemary (10 mL/kg/d) for 1 week (rosemary group), and the other received normal saline for the same period of time (reperfusion group). Reperfusion injury was induced by bilateral occlusion of the renal artery and vein for 30 minutes and reperfusion for 24 hours. Examination of oxidative stress was done, including measurement of malondialdehyde and ferric reducing antioxidant power in urine and blood samples. Histological studies were performed on excised kidneys. RESULTS: The comparison between the rosemary and reperfusion groups indicated significant reductions in the levels of plasma creatinine, blood urea nitrogen, and absolute urinary excretion of sodium in the rosemary group. Similarly, the rosemary group presented a significant decrease in malondialdehyde and a significant increase in ferric-reducing antioxidant power. Histopathological examinations showed significant reductions in vascular congestion and cells exfoliation in the rosemary group, in comparison with the reperfusion group. CONCLUSIONS: Oral administration of the aqueous extract of rosemary prior to ischemia-reperfusion is effective in reducing functional and histopathological complications associated with acute kidney failure.