Role of adipokines in embryo implantation.

Embryo implantation is a complex process in which multiple molecules acting together under strict regulation. Studies showed the production of various adipokines and their receptors in the embryo and uterus, where they can influence the maternal-fetal transmission of metabolites and embryo implantation. Therefore, these cytokines have opened a novel area of study in the field of embryo-maternal crosstalk during early pregnancy. In this respect, the involvement of adipokines has been widely reported in the regulation of both physiological and pathological aspects of the implantation process. However, the information about the role of some recently identified adipokines is limited. This review aims to highlight the role of various adipokines in embryo-maternal interactions, endometrial receptivity, and embryo implantation, as well as the underlying molecular mechanisms.

Toxic effect of light on oocyte and pre-implantation embryo: a systematic review.

In the female reproductive tract, oocytes and embryos are in a dark environment, while during the in vitro fertilization (IVF) they are exposed to various visible and invisible lights such as daylight, microscope, and laminar hood fluorescent lights. Studies have shown that light could damage cellular compartments of oocytes and embryos and consequently decrease rates of fertilization, development, and blastocyst formation. However, due to the lack of consensus about the effects of light on the embryos, and subsequently the inability to make definitive decisions regarding the light exposure management to improve IVF results, in the present study, we systematically reviewed the effect of light with different wavelengths and intensities on pre-implantation embryos. The toxic impact of light depends on the wavelength, intensity, and duration of light exposure and also the stage of embryo. Therefore, reducing the observation time of embryos out of the incubator and also using light filters can alleviate the detrimental effect of light in IVF labs.

Heat stress aggravates oxidative stress, apoptosis, and endoplasmic reticulum stress in the cerebellum of male C57 mice.

BACKGROUND: The current study was set to assess the effect of heat stress exposure on oxidative stress, apoptosis, and endoplasmic reticulum stress markers in the cerebellum of male mice. METHODS: Fifty male C57BL/6 mice were assigned to five groups of (I) control, (II) heat stress (HS)7, (III) HS14, (IV) HS21, and (V) HS42 groups. Animals in the control group were not exposed to HS. Mice in the II-V groups were exposed to HS once a day over 7, 14, 21, and 42 days, respectively. Cerebellar reactive oxygen species (ROS) levels, expression of heat shock protein (HSP)70 and caspase 3 as well as endoplasmic reticulum stress-related proteins (PERK, p-PERK, CHOP, and Full-length ATF-6) expression were determined on the 7th, 14th, 21st, and 42nd days. RESULTS: ROS levels and HSP70 expression increased following HS on the 14th, 21st, and 42nd days and the 7th, and 14th days with a peak level of expression on the 14th day following HS. HSP70 levels decreased afterward on the 21st and 42nd days compared with the control group. Besides, exposure to HS for 14, 21, and 42 days resulted in a significant increase in the CHOP and p-PERK levels in the cerebellum compared with the control group. Heat exposure also increased protein expression of cleaved caspase 3 and active ATF-6/Full-length ATF-6 on the 21st and 42nd days in the cerebellum compared with the control animals. CONCLUSION: These findings indicated that chronic HS augmented oxidative stress, endoplasmic reticulum stress, and apoptosis pathways in the cerebellum of mice.

microRNAs in the pathogenesis of non-obstructive azoospermia: the underlying mechanisms and therapeutic potentials.

miRNAs are involved in different biological processes, including proliferation, differentiation, and apoptosis. Interestingly, 38% of the X chromosome-linked miRNAs are testis-specific and have crucial roles in regulating the renewal and cell cycle of spermatogonial stem cells. Previous studies demonstrated that abnormal expression of spermatogenesis-related miRNAs could lead to nonobstructive azoospermia (NOA). Moreover, differential miRNAs expression in seminal plasma of NOA patients has been reported compared to normozoospermic men. However, the role of miRNAs in NOA pathogenesis and the underlying mechanisms have not been comprehensively studied. Therefore, the aim of this review is to mechanistically describe the role of miRNAs in the pathogenesis of NOA and discuss the possibility of using the miRNAs as therapeutic targets.Abbreviations: AMO: anti-miRNA antisense oligonucleotide; AZF: azoospermia factor region; CDK: cyclin-dependent kinase; DAZ: deleted in azoospermia; ESCs: embryonic stem cells; FSH: follicle-stimulating hormone; ICSI: intracytoplasmic sperm injection; JAK/STAT: Janus kinase/signal transducers and activators of transcription; miRNA: micro-RNA; MLH1: Human mutL homolog l; NF-κB: Nuclear factor-kappa B; NOA: nonobstructive azoospermia; OA: obstructive azoospermia; PGCs: primordial germ cells; PI3K/AKT: Phosphatidylinositol 3-kinase/protein kinase B; Rb: retinoblastoma tumor suppressor; ROS: Reactive Oxygen Species; SCOS: Sertoli cell-only syndrome; SIRT: sirtuin; SNPs: single nucleotide polymorphisms; SSCs: spermatogonial stem cells; TESE: testicular sperm extraction; TGF-ß: transforming growth factor-beta.

Hormonal markers as noninvasive predictors of sperm retrieval in non-obstructive azoospermia.

Non-obstructive azoospermia (NOA) is one of the leading causes of male factor infertility, which results from impaired spermatogenesis. Currently, the sole feasible therapeutic option for men with NOA to father their biologic children is sperm retrieval by testicular sperm extraction (TESE) approaches followed by an intracytoplasmic sperm injection program. Nevertheless, the rate of sperm retrieval from NOA men following TESE has remained as low as 50%, leading to a significant number of unsuccessful TESE operations. Given that TESE is associated with multiple side effects, the prediction of TESE outcome preoperatively can abolish unnecessary operations and thereby prevent NOA patients from sustaining adverse side effects. As the process of spermatogenesis is under the regulation of hormones, the hormonal profile of serum and/or seminal plasma may contain useful information about spermatogenesis status and can potentially predict the chance of sperm retrieval from NOA patients. A large body of literature is available on the predictive capability of different serum and seminal plasma hormones such as FSH, LH, testosterone, inhibin B, AMH, estradiol, prolactin, and leptin in a stand-alone basis or combinational fashion with respect to the TESE outcome. The present review aimed to evaluate the potential of these hormonal markers as noninvasive predictors of sperm retrieval in men with NOA.

Omics in Seminal Plasma: An Effective Strategy for Predicting Sperm Retrieval Outcome in Non-obstructive Azoospermia.

Non-obstructive azoospermia (NOA) is a severe form of male factor infertility resulting from the impairment of sperm production. Surgical sperm retrieval followed by intracytoplasmic sperm injection (ICSI) is the only alternative for NOA patients to have their own genetic children. Nevertheless, due to an approximately 50% chance of success, harvesting sperm from these patients remains challenging. Thus, discovering noninvasive biomarkers, which are able to reliably predict the probability of sperm acquisition, not only can eliminate the risk of surgery but also can lower the costs of NOA diagnosis and treatment. Seminal plasma is the non-cellular and liquid portion of the ejaculate that consists of the secretions originating from testes and male accessory glands. In past years, a wide range of biomolecules including DNAs, RNAs, proteins, and metabolic intermediates have been identified by omics techniques in human seminal plasma. The current review aimed to briefly describe genomic, transcriptomic, proteomic, and metabolomic profiles of human seminal plasma in an attempt to introduce potential candidate noninvasive biomarkers for sperm-retrieval success in men with NOA.

Role of adipokines in the ovarian function: Oogenesis and steroidogenesis.

Adipokines are mainly produced by adipose tissue; however, their expression has been reported in other organs including female reproductive tissues. Therefore, adipokines have opened new avenues of research in female fertility. In this regard, studies reported different roles for certain adipokines in ovarian function, although the role of other recently identified adipokines is still controversial. It seems that adipokines are essential for normal ovarian function and their abnormal levels could be associated with ovarian-related disorders. The objective of this study is to review the available information regarding the role of adipokines in ovarian functions including follicular development, oogenesis and steroidogenesis and also their involvement in ovary-related disorders.

A closer look at the role of insulin for the regulation of male reproductive function.

While insulin demonstrates to have a considerable influence on the reproductive system, there are various unanswered questions regarding its precise sites, mechanisms of action, and roles for the developing and functioning of the adult male reproductive system. Apart from its effects on glucose level, insulin has an important role in the reproductive system directly by binding on insulin and IGF receptors in the brain and testis. To date, however, the effect of insulin or its alterations on blood-testis-barrier, as an important regulator of normal spermatogenesis and fertility, has not yet been studied. This review aimed to focus on the experimental and clinical studies to describe mechanisms by which insulin affects the hypothalamic-pituitary-gonadal (HPG) axis, testicular cells, spermatozoa, and sexual behavior. Moreover, we discussed the mechanism and impact of insulin changes in type 1 (insulin deficiency along with persisted or even increased sensitivity) and 2 (insulin resistance along with increased insulin level at the early stages of disease) diabetes and obesity on the male reproductive tract.

Sodium nitrate preconditioning prevents progression of the neuropathic pain in streptozotocin-induced diabetes Wistar rats.

PURPOSE: The purpose of the study was to evaluate the possible protective effects of low dose sodium nitrate preconditioning on the peripheral neuropathy in streptozotocin (STZ)-induced diabetic model. METHODS: Male Wistar rats were randomly divided into five groups: control (no intervention), control treated sodium nitrate (100 mg/L in drinking water), diabetic (no intervention), diabetic treated NPH insulin (2-4 U), and diabetic treated sodium nitrate (100 mg/L in drinking water). Diabetes was induced by intraperitoneal injection of STZ (60 mg/kg). All interventions were done for 60 days immediately following diabetes confirmation. Thermal and mechanical algesia thresholds were measured by means of hot-plate test, von Frey test, and tail-withdrawal test before the diabetic induction and after diabetes confirmation. At the end of the experiment, serum NOx level and serum insulin level were assessed. Blood glucose concentration and body weight have recorded at the base and duration of the experiment. RESULTS: Both hypoalgesia, hyperalgesia along with allodynia developed in diabetic rats. Significant alterations including, decrease in tail withdrawal latency (30th day), decreased mechanical threshold (60th day), and an increase in hot plate latency (61st day) were displayed in diabetic rats compared to control rats. Nitrate and insulin preconditioning produced protective effects against diabetes-induced peripheral neuropathy. Data analysis also showed a significant increase in glucose level as well as a considerable reduction in serum insulin and body weight of diabetic rats, which restored by both insulin and nitrate preconditioning. CONCLUSION: Sodium nitrate preconditioning produces a protective effect in diabetic neuropathy, which may be mediated by its antihyperglycemic effects and increased serum insulin level.

Can troxerutin pretreatment prevent testicular complications in prepubertal diabetic male rats?

OBJECTIVE: The vast majority of type 1 diabetes leads to a higher prevalence of reproductive system's impairments. Troxerutin has attracted much attention owing to its favorable properties, including antihyperglycemic, anti-inflammatory, and antiapoptotic effects. This investigation was proposed to evaluate whether pretreatment with troxerutin could prevent apoptosis-induced testicular disorders in prepubertal diabetic rats. METHODS: Fifty prepubertal male Wistar rats were randomly allocated into five groups: control (C), troxerutin (TX), diabetic (D), diabetic+troxerutin (DTX), and diabetic+insulin (DI). Diabetes was induced by 55 mg/kg of streptozotocin applied intraperitoneally. In TX and DTX groups, 150 mg/kg troxerutin was administered by oral gavage. Diabetic rats in DI group received 2-4 U NPH insulin subcutaneously. Troxerutin and insulin treatments were begun immediately on the day of diabetes confirmation. After 30 days, the testicular lipid peroxidation and antioxidant activity, apoptosis process, and stereology as well as serum glucose and insulin levels were assessed. RESULTS: The results showed that diabetes caused a significant increase in the blood glucose, the number of TUNEL positive cells and tubules, and the malondialdehyde level as well as a significant decrease in serum insulin level compared to controls. The stereological analysis also revealed various alterations in diabetic rats compared to controls. Troxerutin treatment improved these alterations compared to the diabetic group. CONCLUSION: Troxerutin-pretreatment may play an essential role in the management of the type-1 diabetes-induced testicular disorders by decreasing blood glucose and modulating apoptosis.

Effects of bacteria on male fertility: Spermatogenesis and sperm function.

Bacterial infection can negatively affect different parts of the male genital tract and subsequently cause impaired spermatogenesis and male fertility. However, most of the previous studies have focused on the infected organs of the male genital tract and there are not many studies that investigated the direct effect of bacteria on sperm and their mechanism of action. Interestingly, bacteria can induce different damages on sperm cells such as DNA fragmentation, cell membrane peroxidation, and acrosome impairment. Such negative effects can be mediated by bacteria-secreted toxins and metabolites or by direct attachment of bacteria on the sperm cells and subsequent activation of signaling pathways related to oxidative stress, apoptosis, and inflammation. These bacteria-induced changes can impair semen parameters and subsequently cause infertility. Given the significant destructive effect of some bacteria on sperm function and male fertility, in this study, we reviewed the impact of male urogenital bacteria on spermatogenesis and sperm functions as well as the underlying mechanisms by which the bacteria can damage sperm.

The effect of prolonged dietary sodium nitrate treatment on the hypothalamus-pituitary-gonadal axis and testicular structure and function in streptozotocin-induced diabetic male rats.

The aim of this study was to evaluate the effect of prolonged dietary nitrate supplementation on the gonadotropin level, testicular histology and morphometry, expression of miR-34b and p53 mRNA, and spermatogenesis in streptozotocin-induced diabetic male rats. METHODS: Fifty male Wistar rats were divided into 5 groups: Control (C), control + nitrate (CN), diabetes (D), diabetes + insulin (DI), and diabetes + nitrate (DN). Diabetes was induced using 45 mg kg-1 of streptozotocin intraperitoneally. Rats in the CN and DN groups were administered sodium nitrate in drinking water (100 mg L-1). NPH insulin (2-4 U d-1) was injected subcutaneously in the DI group for 2 months. Nitrate and insulin supplementation was started one month after confirmation of diabetes. RESULTS: Nitrate supplementation in the DN group significantly increased the body weight (p < 0.05), sperm parameters (p < 0.001), indices of spermatogenesis (p < 0.001), and testis histopathology as well as decreased the blood glucose level (p < 0.001) compared to the untreated diabetic group, although it had no significant effect on testicular parameters, LH and FSH levels. Nitrate administration in the DN group also decreased miR-34b (p < 0.001) and p53 mRNA (p < 0.001) expression, and increased serum insulin and NOx levels compared to the untreated diabetic rats. CONCLUSIONS: Chronic nitrate supplementation in streptozotocin-induced diabetic rats improved fertility parameters, which may be associated with increased miR-34b and decreased p53 mRNA.

Evaluation of ameliorative effect of sodium nitrate in experimental model of streptozotocin-induced diabetic neuropathy in male rats.

OBJECTIVE: Diabetes induces sensory symptoms of neuropathy as positive (hyperalgesia), negative (hypoalgesia), or both. METHODS: In the present study, fifty male Wistar rats were allocated to five groups: control, control+nitrate, diabetes, diabetes+insulin, and diabetes+nitrate. Thirty days after diabetes confirmation, insulin (2-4 U/day) was injected subcutaneously in diabetes+insulin group and nitrate (100 mg/l) was added into drinking water of the control+nitrate and diabetes+nitrate groups for a period of 2 months. In order to assess the mechanical and thermal algesia, tail immersion, hot plate, and von Frey tests were performed. The serum insulin levels were determined with insulin ELISA Kit. Serum level of NOx was determined by the Griess method. RESULTS: Both thermal and mechanical nociceptive thresholds showed a significant decrease (p<0.05) which was followed by a significant increase (p<0.01) in the thermal nociceptive threshold in the diabetes group. Chronic nitrate or insulin treatment led to a significant decrease (p<0.01) in blood glucose levels, as well as a significant (p<0.05) increase in the body weight and serum NOx. Moreover, nitrate treatment significantly increased serum insulin levels (p<0.001) compared to the other groups. CONCLUSION: Chronic nitrate treatment modified the thermal and mechanical sensitivities in diabetic animals.

Administration of troxerutin improves testicular function and structure in type-1 diabetic adult rats by reduction of apoptosis.

OBJECTIVE: The glucose-reducing effects of troxerutin was previously proven. This study was conducted to evaluate troxerutin effect on testicular structure and spermatozoid parameters in type-1 diabetic adult male rats. MATERIALS AND METHODS: Fifty male Wistar rats were randomly classified into 5 groups as follows: control (C), troxerutin (T), diabetic (DM), troxerutin-treated DM (DT) and insulin-treated DM (DI). Testicular structure, apoptosis, lipid peroxidation and antioxidant activity, and spermatozoid parameters were assessed 4 weeks after initiation of the interventions. RESULTS: The results revealed that diabetes caused testicular stereological changes and significantly increased blood glucose level, testicular MDA content and apoptosis but decreased insulin level, testicular GPX activity, and sperm parameters compared to controls (p<0.001 to p<0.05). Administration of troxerutin and insulin could significantly reduce blood glucose level and improve testicular MDA content, testicular stereological findings and apoptosis compared to DM group (p<0.001 to p<0.05). CONCLUSION: Taken together, troxerutin, comparable to insulin, effectively improved DM-induced testicular dysfunction and sperm parameters in diabetic rats and these effects might be mediated through troxerutin's anti-apoptotic effects.

Beneficial treatment effects of dietary nitrate supplementation on testicular injury in streptozotocin-induced diabetic male rats.

RESEARCH QUESTION: Do low doses of dietary nitrate help to attenuate the progression of diabetic reproductive disorders in streptozotocin-induced diabetic male rats? DESIGN: Fifty male Wistar rats were divided into five groups: controls receiving distilled water; controls receiving 100 mg/l nitrate in distilled water; diabetic rats receiving distilled water; diabetic rats receiving insulin 2-4 U/day of neutral protamine hagedorn insulin; and diabetic rats receiving 100 mg/l nitrate in distilled water. Diabetes was induced by 45 mg/kg streptozotocin. Nitrate and insulin treatment were started 4 weeks after diabetes induction for 8 weeks. Serum insulin, nitrogen oxide, stereology of testis, apoptosis, sperm parameters, and mRNA expression of Pdcd4, Pacs2, p53 and miR-449a were assessed at the end of the study. RESULTS: Blood glucose, apoptotic index of seminiferous tubules and expression of p53, Pdcd4, and Pacs2 mRNA were significantly higher in the diabetic rats (P < 0.001). Decreased body weight, serum insulin and nitrogen oxide level, and miR-449a were observed in the diabetic group (P < 0.01 for insulin; P < 0.001 for others). Most sperm parameters and stereological results differed between diabetic and control rats; nitrate recovered almost all these alterations, including dead spermatozoa, sperm motility grade, sperm deformity index, spermatozoa with damaged DNA, malformations in abnormal spermatozoa, total volume of seminiferous tubule, germinal epithelium, capsule, lumen, interstitial tissue, seminiferous tubule diameter, germinal epithelium height, the number of spermatogenic, Sertoli and Leydig cells. CONCLUSIONS: Treatment with sodium nitrate could modulate apoptosis, which is a major cause of diabetic testicular disorder. These experiments suggest that nitric oxide plays an important role in the function of the reproductive system.

Troxerutin affects the male fertility in prepubertal type 1 diabetic male rats.

OBJECTIVES: Diabetes can gradually cause damage to the function and structure of male gonads. This survey was conducted to investigate the effect of troxerutin on hormonal changes, serum oxidative stress indices, and testicular function and structure in prepubertal diabetic rats. MATERIALS AND METHODS: Fifty prepubertal (6 weeks old) male Wistar rats were divided into five groups including Control, Troxerutin, Diabetic, Diabetic+Troxerutin, and Diabetic+Insulin. Type I diabetes was induced by 55 mg/kg of streptozotocin intraperitoneally. The groups were treated with 150 mg/kg/day troxerutin via oral gavage or 4-6 IU/day insulin via subcutaneous injection for 4 consecutive weeks. Blood sugar (BS) and serum levels of insulin, FSH, LH, testosterone, glutathione peroxidase (GPX), superoxide dismutase (SOD), malondialdehyde (MDA), and total antioxidant capacity (TAC) were analyzed. Testis and epididymis were removed for histopathologic study and analysis of sperm parameters. RESULTS: Troxerutin significantly reduced the BS in the diabetic group similar to insulin but could not affect insulin, FSH, or LH significantly. Troxerutin caused a significant increase in testosterone and GPX but had no significant effect on serum MDA, TAC, and SOD levels. In addition, troxerutin had a better effect than insulin on diabetes-induced testicular structural damage. Sperm analysis results also revealed that troxerutin and insulin could improve sperm number, motility, and viability in diabetic rats. CONCLUSION: According to these results, it can be derived that administration of troxerutin is a suitable protective strategy for side effects of diabetes in testis of prepubertal diabetic male rats.

Protective effects of sodium nitrate against testicular apoptosis and spermatogenesis impairments in streptozotocin-induced diabetic male rats.

AIMS: As nitric oxide (NO) production is essential for insulin signaling, glucose uptake, endothelial function, and regulation of apoptosis, the loss of bioavailable NO may be a mechanism underlying the development of diabetes complication. Dietary nitrate acts as a substrate for NO generation, thus serving as a physiological source of NO. This study evaluated the therapeutic effects of nitrate supplementation on the apoptosis-induced testicular disorders in diabetic rats. MAIN METHODS: Fifty male Wistar rats were divided into five groups; control, control with 100 mg/L nitrate in distilled drinking water, diabetes, diabetes treated with 2-4 U/day NPH insulin, diabetes treated with 100 mg/L nitrate in distilled drinking water. After 8 weeks, blood samples, testis, and epididymis were collected to assess the apoptosis process and the stereology of testis tissue, sperm motility, morphology and DNA fragmentation, and also mRNA expression of miR-449a, p53, Pdcd4, and Pacs2 mRNA, as well as serum glucose, insulin, and NOx levels were investigated. KEY FINDINGS: The results of this study indicated that nitrate treatment ameliorated the sperm parameters, testicular morphometrical and stereological alterations, reduced blood glucose, the number of TUNEL positive cells and tubules, and testicular expressions of p53, Pdcd4, and Pacs2 mRNA as well as increased body weight, serum insulin and NOx levels, and testicular expression of miR-449a in streptozotocin-induced diabetic rats. SIGNIFICANCE: Our in vivo evidence revealed that nitrate treatment may has a favorable effect as an exogenous NO donor on experimental diabetic testicular damages in which NO bioavailability is impaired.

Two months sodium nitrate supplementation alleviates testicular injury in streptozotocin-induced diabetic male rats.

NEW FINDINGS: What is the central question of this study? Can low-dose inorganic nitrate supplementation prevent testicular structural and functional alterations in streptozotocin-induced type 1 diabetic male rats? What is the main finding and it's important? Treatment with a low dose of inorganic nitrate for 2 months had protective effects on the male reproductive system in diabetic rats including improved body weight loss, sperm and testis parameters, spermatogenesis index and testicular histology as well as increased serum testosterone levels. These favourable effects may be associated with increased serum insulin and decreased serum glucose, and with modulation of apoptosis in testis. ABSTRACT: Inorganic nitrate supplementation is a possible therapeutic agent in diabetes. The aim of this study was to evaluate the effect of nitrate on the reproductive system in streptozotocin-induced diabetic male rats. Fifty male Wistar rats were allocated randomly to five groups: control (C), control plus nitrate (CN), diabetic (D), diabetic plus insulin (DI) and diabetic plus nitrate (DN). Sodium nitrate was administered for 2 months in the drinking water (100 mg l-1 ) of the CN and DN groups. Insulin was injected at 2-4 U daily in the DI group. Serum glucose level and body weight were measured at the beginning of the study and at regular intervals. At the end of the study, serum levels of glucose, insulin, nitrogen oxides (NOx), luteinizing hormone (LH), follicle-stimulating hormone (FSH) and testosterone were assessed as well as sperm parameters, testis morphometry and histology, and testicular miR-34b and p53 mRNA expression. Nitrate treatment in diabetic rats significantly improved sperm parameters, epididymal weight, spermatogenesis and testicular histology as well as decreasing serum glucose and testicular p53 gene and miR-34b expression, although it had no effect on serum LH and FSH levels. In diabetic rats, serum insulin and NOx, body weight, testicular and epididymal weight, sperm count and motility, testis morphology, spermatogenesis indices, Johnsen's score, and testosterone were significantly lower than in controls. Nitrate administration increased serum insulin, NOx and testosterone levels in the DN group. Consuming water supplemented with sodium nitrate could improve diabetes-induced testicular functional and structural disorders; these favourable effects may be related to increased serum insulin and decreased serum glucose, as well as modulation of apoptosis in testis.

The Effect of Regular Moderate Exercise on miRNA-192 Expression Changes in Kidney of Streptozotocin-Induced Diabetic Male Rats.

PURPOSE: The purpose of this study was to investigate the regular moderate exercise effect on the miR-192 expression changes in kidney of Streptozotocin- induced diabetic rats. METHODS: Forty adult male Wistar rats were divided into four groups of 10, including Sedentary Control group, Healthy 60 days Exercise group, diabetic group and Diabetic 60 days Exercise. Diabetes was induced by injection of 60 mg/kg Streptozotocin and after 48 hour blood glucose levels higher than 250 mg/dl were included to diabetic rats. After 48 hour of induction diabetes, exercise protocol was begun. Animals performed 5 days of consecutive treadmill exercise (60 min/day) with 22 m/min speeds for 60 days. Kidney of the rats has removed and MicroRNA was extracted from kidney using miRCURY(TM) RNA isolation kit. RESULTS: Exercise upregulated miR-192 expression level significantly in the kidney of diabetic rats in comparison to healthy group. There is not any significant change in miR-192 expression in diabetic 60 days exercise compared to control group. CONCLUSION: These results may indicate that exercise can help to prevent the progression of diabetic nephropathy.