Publications by authors named "Razi Mazdak"

60 Publications

High-fat diet-induced obesity amplifies HSP70-2a and HSP90 expression in testicular tissue; correlation with proliferating cell nuclear antigen (PCNA).

Life Sci 2021 May 19;279:119633. Epub 2021 May 19.

Department of Basic Sciences, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran. Electronic address:

Aims: Current study was conducted to uncover the effect of high-fat diet (HFD)-induced obesity on heat shock proteins 70-2a and 90 expression levels and to investigate the network between these proteins with PCNA expression, endocrine status of testicular tissue and nucleotide backbone damages.

Main Methods: For this purpose, 20 mature male Wistar rats were divided into two groups of control and HFD-received obese animals (n = 10/group). After 8 weeks from obesity approval, the animals were euthanized. The expression levels of Hsp70-2a, Hsp90 and PCNA were analyzed by qRT-PCR and immunohistochemical staining techniques. The Leydig cell distribution/mm of interstitial tissue, serum level of testosterone, testicular total antioxidant capacity (TAC), and mRNA and DNA damage were investigated.

Key Findings: The obese (HFD-received) animals represented a remarkable (p < 0.05) increment in the mRNA levels of hsp70-2a and Hsp90, and the percentages of Hsp70-2a and Hsp90 cells/seminiferous tubules with the same criteria. The PCNA mRNA level and the percentage of PCNA cells were decreased in the obese (HFD-received) group. The obesity, significantly decreased testicular TAC and with no effect on the Leydig cell distribution, but by reducing their steroidogenic activity resulted in a remarkable (p < 0.05) reduction in serum testosterone level. Finally, severe mRNA and DNA damage were revealed in the obese (HFD-received) group.

Significance: Therefore, considering massive testicular DNA damage in the obese (HFD-received) animals, we can conclude that an increased expression of Hsp70-2a and Hsp90 with no harmony with PCNA could not properly maintain the cellular DNA integrity and/or appropriately finalize the DNA repair process.
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http://dx.doi.org/10.1016/j.lfs.2021.119633DOI Listing
May 2021

ROS and metabolomics-mediated autophagy in rat's testicular tissue alter after exercise training; Evidence for exercise intensity and outcomes.

Life Sci 2021 Jul 3;277:119585. Epub 2021 May 3.

Department of basic Sciences, Division of Histology & Embryology, Faculty of Veterinary Medicine, P.O.BOX: 1177, Urmia University, Urmia, Iran. Electronic address:

Aims: Oxidative damage and altered metabolic reactions are suspected to initiate the autophagy. The exercise training significantly impacts testicular antioxidant and metabolic potentials. However, the underlying mechanism(s) that the exercise-induced alterations can affect the autophagy markers remained unknown. This study explored the effect of exercise training on antioxidant and metabolic statuses of testicular tissue and uncovered the possible cross-link between these statuses and autophagy-inducers expression.

Main Methods: Wistar rats were divided into sedentary control, low (LICT), moderate (MICT), and high (HICT) intensity continuous training groups. Following 8 weeks of training, the testicular total antioxidant capacity (TAC), total oxidant status (TOS), glutathione (GSH), and NADP/NADPH as oxidative biomarkers along with intracytoplasmic carbohydrate and lipid droplet patterns, lactate dehydrogenase (LDH) activity, and lactate as metabolic elements were assessed. Finally, the autophagy-inducers expression and sperm count were examined.

Key Findings: With no significant impact on the oxidative biomarkers and metabolic elements, the LICT and MICT groups exhibited statistically unremarkable (p < 0.05) impacts on spermatogenesis differentiation, spermiogenesis ratio, and sperm count while increased the autophagy-inducers expression. Reversely, the HICT group, simultaneous with suppressing the antioxidant biomarkers (TAC↓, GSH↓, TOS↑, NADP/NADPH↑), significantly (p < 0.05) reduced the testicular LDH activity and lactate level, changed the intracytoplasmic carbohydrate and lipid droplet's pattern, and amplified the classical autophagy-inducers p62, Beclin-1, autophagy-related gene (ATG)-7, and light chain 3 (LC3)-II/I expression.

Significance: The autophagy-inducers overexpression has occurred after HICT induction, most probably to eliminate the oxidative damage cargoes, while increased to maintain the metabolic homeostasis in the LICT and MICT groups.
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http://dx.doi.org/10.1016/j.lfs.2021.119585DOI Listing
July 2021

Effects of liraglutide on sperm characteristics and fertilization potential following experimentally induced diabetes in mice.

Vet Res Forum 2021 15;12(1):109-116. Epub 2021 Mar 15.

Department of Basic Sciences, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran.

The current study was conducted to analyze the dose-dependent effects of liraglutide against the diabetes-induced detrimental impact on sperm parameters and fertilization potential. For this purpose, 42 adult male mice were randomly divided into control (with no intervention) and experimental groups. Next, the experimental group was subdivided into diabetic, 1.20 mg kg liraglutide-received diabetic, 1.80 mg kg liraglutide-received diabetic, 1.20 mg kg liraglutide-received non-diabetic and 1.80 mg kg liraglutide-received non-diabetic groups. All chemicals were administrated subcutaneously. Following 42 days, the animals were euthanized, and sperm samples were collected. The sperm count, motility, viability, DNA integrity, and maturity were analyzed and compared between groups. Moreover, the sperm fertilization potential was investigated by fertilization (IVF). For this purpose, the preimplantation embryo development at 2-cell, 4-cell, morula, and blastocyst stages was investigated and compared. Observations revealed that diabetes significantly diminished sperm count, motility, viability, chromatin condensation, and DNA integrity percentages a control group. On the other hand, 1.20 mg kg and 1.80 mg kg of liraglutide did not improve sperm motility and viability, while ameliorated sperm count and chromatin condensation and DNA integrity in diabetic animals. The diabetic animals represented diminished preimplantation embryo development, which was not altered in liraglutide-received groups. In conclusion, at least in administrated doses, liraglutide could not improve the sperm viability and motility and, via this mechanism, could not induce an appropriate/beneficial effect on IVF outcome.
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http://dx.doi.org/10.30466/vrf.2019.96822.2315DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8094147PMC
March 2021

Fabrication of chitosan-based electrospun nanofiber scaffold: Amplification of biomechanical properties, structural stability, and seeded cell viability.

Vet Res Forum 2021 15;12(1):25-32. Epub 2021 Mar 15.

Nanotechnology Research Center, Urmia University, Urmia, Iran.

The cell scaffolds should structurally be manufactured similar to the target tissue's extracellular matrix. This property should be maintained until cell differentiation. For this purpose, in the current study, electrospun nanofiber (EN) of chitosan (Ch)/polyvinyl alcohol (PVA), as a tissue-friend scaffold, was fabricated by electrospinning in different formulations and borax was utilized as an innovative cross-linking agent to up-regulate the structural and biomechanical properties. The weight loss, water absorbability, structural stability, tensile strength and biocompatibility of borax-included and non-included ENs were compared. The finest morphology, weight loss, water absorbability, structural stability in an aqueous environment, tensile strength and cell viability were found in the borax-included EN containing Ch50.00%v/PVA50.00%v. Moreover, The ENs exhibited appropriate antibacterial properties against Gram-positive and Gram-negative bacteria. In conclusion, borax can be used to improve the mechanical and biocompatibility features of the Ch/PVA-based ENs. Furthermore, it could be suggested that borax-included Ch/PVA ENs can exhibit high appropriate biological properties, candidate them as an appropriate scaffold in the field of tissue engineering. However, trials are needed to clearly their side effects and advantages.
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http://dx.doi.org/10.30466/vrf.2020.123047.2893DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8094139PMC
March 2021

The molecular mechanism behind insulin protective effects on testicular tissue of hyperglycemic rats.

Life Sci 2021 Jul 27;277:119394. Epub 2021 Mar 27.

Division of Pharmacology and Toxicology, Department of Basic Science, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran.

Aims: The present study assessed the possible mechanisms by which the insulin regulates the heat shock (HSPs) and transitional proteins expression and consequently ameliorates the oxidative stress-induced damages in germ and sperm cells DNA contents.

Main Methods: Mature male Wistar rats were distributed into control, Hyperglycemia-induced (HG) and insulin-treated HG-induced (HG-I) groups. Following 8 weeks from HG induction, testicular total antioxidant capacity (TAC), immunoreactivity of 8-oxodG, germ cells mRNA damage, Hsp70-2a, Hsp90, transitional proteins 1 and 2 (TP-1 and -2) mRNA and protein expressions were analyzed. Moreover, the sperm chromatin condensation was assessed by aniline-blue staining, and DNA integrity of germ and sperm cells were analyzed by TUNEL and acrdine-orange staining techniques.

Key Findings: The HG animals exhibited significant (p < 0.05) reduction in TAC, HSp70-2a, TP-1 and TP-2 expression levels, and increment in 8-oxodG immunoreactivity, mRNA damage, and Hsp90 expression. However, insulin treatment resulted in (p < 0.05) enhanced TAC level, Hsp70-2a, Hsp90, TP-1 and TP-2 expressions, besides reduced 8-oxodG immunoreactivity and mRNA damage compared to the HG group (p < 0.05). The chromatin condensation and the germ and sperm cells DNA fragmentation were decreased in HG-I group.

Significance: Insulin treatment amplifies the testicular TAC level, improves the Hsp70-2a, TP-1, and TP-2 expressions, and boosts the Hsp90-mediated role in DNA repairment process. Consequently, altogether could maintain the HG-induced DNA integrity in the testicular and sperm cells.
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http://dx.doi.org/10.1016/j.lfs.2021.119394DOI Listing
July 2021

Different continuous exercise training intensities induced effect on sertoli-germ cells metabolic interaction; implication on GLUT-1, GLUT-3 and MCT-4 transporting proteins expression level.

Gene 2021 May 10;783:145553. Epub 2021 Mar 10.

Department of Physiology, Faculty of Medicine, Urmia University of Medical Sciences, Urmia, Iran.

Despite other tissues, the effect of different exercise training protocols (ETPs) on the expression levels of metabolic substrates transmembrane transporters in the testicular tissue, remains completely unexplored. Thus, the effects of low, moderate and high-intensity ETPs on the SCs and germ cells potentials in GLUT-1, GLUT-3 and MCT-4 expression levels was investigated in this study. The animals were assigned into 4 groups, including sedentary control, low-intensity continuous (LICT), moderate-intensity (MICT) and high-intensity (HICT) ETPs-induced groups (n = 6/group). The GLUT-1, GLUT-3 and MCT-4 expressions, cytoplasmic carbohydrate storages of SCs and germ cells, the SCs survival and the spermatogenesis and spermiogenesis rates were assessed. The LICT and MICT did not significantly alter the protein expression levels of GLUT-3 and MCT-4 in the SCs and germ cells, while decreased the GLUT-1 protein content versus the sedentary control animals. In contrast, the HICT remarkably suppressed the GLUT-1 and MCT-4 in both SCs, and germ cells and diminished GLUT-3 in SCs and increased in the germ cells. No significant changes were revealed in the cytoplasmic carbohydrate storage in the LICT and MICT groups, while significantly diminished in the HICT group. The HICT group showed a failed spermatogenesis and spermiogenesis, which were not demonstrated in the sedentary control, LICT and MICT groups. In conclusion, the HICT, by reducing the GLUT-1, GLUT-3 and MCT-4 protein contents in the SCs and reducing the SCs survival, can suppress the glucose transmembrane transport and inhibit the lactate export from SCs, which in turn, ends with failed spermatogenesis and spermiogenesis.
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http://dx.doi.org/10.1016/j.gene.2021.145553DOI Listing
May 2021

Effects of atorvastatin and resveratrol against the experimental endometriosis; evidence for glucose and monocarboxylate transporters, neoangiogenesis.

Life Sci 2021 May 16;272:119230. Epub 2021 Feb 16.

Department of Surgery and Diagnostic Imaging, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran.

The current study was conducted to investigate the therapeutic effects of atorvastatin (ATV) and resveratrol (RVT) in sole and simultaneous forms of administration against the symbiosis between glucose transporters 1 and 3 (GLUT-1 and GLUT-3), monocarboxylate transporters 1 a and 4 (MCT-1 and MCT-4) and neovascularization in ectopic endometrial tissue (EET). For this purpose, the experimental endometriosis was induced in 24 virgin female Wistar rats, and then the rats were divided into non-treated endometriosis-induced (ENDO-sole), AVT-treated (5 mg kg-1), RVT-treated (40 mg kg-1) and AVT +RVT-treated groups (n = 6 rats in each group). Following 28 days from the experimental endometriosis induction, the EETs were collected and the EETs size, neovascularization ratio, and expression levels of GLUT-1, GLUT-3, MCT-1, and MCT-4 were analyzed by qRT-PCR and immunohistochemistry (IHC). The AVT and RVT sole and simultaneous-treated animals exhibited decreased EET sizes and neovascularization. Moreover, the mRNA levels of GLUT-1, GLUT-3, MCT-1, and MCT-4, as well as GLUT-1, GLUT-3, and MCT-4 cells distribution per mm of tissue were decreased in AVT and RVT sole and simultaneous-treated groups. Our findings showed that the AVT and RVT, especially in the simultaneous form of administration, could decrease the neovascularization development in the EETs by suppressing the GLUTs (1 and 3) and MCTs (1 and 4) expressions. Therefore, it can be concluded that the simultaneous administration of AVT and RVT can inhibit the EET's establishment and development through suppressing glycolysis and neovascularization.
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http://dx.doi.org/10.1016/j.lfs.2021.119230DOI Listing
May 2021

Nano-micelle Curcumin; A Hazardous and/or Boosting Agent? Relation with Oocyte Maturation and Pre-implantation Embryo Development in Rats.

Iran J Pharm Res 2020 ;19(2):242-250

Department of Anatomy and Embryology, Faculty of Veterinary Medicine, Urmia University, Iran.

The present study was done to uncover the possible beneficial and/or detrimental effect(s) of nano-micelle curcumin (NMC) on oocyte maturation and pre-implantation embryo development. Forty-eight mature female Wistar rats were assigned to control, 7.5, 15, and 30 mg/kg NMC-receiving (orally, for 48 days) groups. To assess the cumulus-oocyte complexes (COCs), the ovaries were stimulated by administrating (i.p.) a 25 IU of the pregnant mare's serum gonadotropin (PMSG) hormone. Following 48-h, 15 IU of hCG was injected (i.p.), and the COCs were taken after 16-18-h. To analyze the pre-implantation embryo development ratio, the sperms were collected from clinically healthy male Wistar rats, and 3.0-3.6 × 106 per mL was added into the fertilization drop. The animals in 7.5 mg/kg NMC-receiving group exhibited a higher oocyte number control and other NMC-receiving groups. The NMC, in a dose-dependent manner, decreased the Zygote, 2-cell, blastocyst percentages, as well as hatched embryos, compared to the control group ( 0.05). The 15 and 30 mg/kg NMC-receiving groups represented a remarkable enhancement in type I arrest. Meanwhile, a significant ( 0.05) reduction was revealed in type III embryo arrest in the same groups. The NMC, at 7.5 mg/kg potentially enhances the oocyte number, while it fairly reduces the pre-implantation embryo development, even when it is administrated in dose levels of 7.5 mg/kg and/or higher. Although more studies are needed, the NMC could be considered as a suppressor of fertility potential, when consumed chronically even in low doses.
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http://dx.doi.org/10.22037/ijpr.2019.14799.12671DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7667555PMC
January 2020

Varicocoele and oxidative stress: New perspectives from animal and human studies.

Andrology 2021 03 6;9(2):546-558. Epub 2020 Dec 6.

Department of Animal Biotechnology, Reproductive Biomedicine Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran.

Background: Varicocoele (VCL), one of the main causes of male subfertility, negatively affects testicular function. Due to limited access to human testicular tissue, animal model studies have been used to evaluate molecular and, recently, epigenetic changes attributed to pathophysiology induced by VCL.

Objectives: This review aims to provide an update on the latest findings regarding the link between VCL-induced biochemical stress and molecular changes in germ cells and spermatozoa. Endocrine and antioxidant status, testicular chaperone-specific hemostasis failure, altered testicular ion balance, metabolic disorders, and altered carbon cycling during spermatogenesis are among the many features that will be presented.

Discussion: Literature review coupled with our own findings suggests that ionic imbalance, hypoxia, hyperthermia, and altered blood flow could lead to severe chronic oxidative and nitrosative stress in patients with VCL leading to defective spermatogenesis and impairment of the integrity of all sperm cell components and compartments down to the epigenetic information they carry.

Conclusion: Since oxidative stress is an important feature of the reproductive pathology of VCL, therapeutic strategies such as the administration of appropriate antioxidants could be undertaken as a complementary non-invasive treatment line.
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http://dx.doi.org/10.1111/andr.12940DOI Listing
March 2021

Insight into the mechanism of aspartame-induced toxicity in male reproductive system following long-term consumption in mice model.

Environ Toxicol 2021 Feb 20;36(2):223-237. Epub 2020 Sep 20.

Department of Comparative Biomedical Sciences, Shiraz University of Medical Sciences, Shiraz, Iran.

Aspartame is one of the most common consumed artificial sweeteners utilized in many food products and beverages. It has been indicated that long-term consumption of aspartame leads to reproductive toxicity but its mechanism is not well-clear. In this study we investigated mechanism of aspartame-induced reproductive toxicity in male mice. For this purpose, 36 NMRI mature male mice received three doses of 40, 80, and 160 mg/kg body weight of aspartame, respectively per day by gavage for 90 days and also a control group was considered which received 0.5 mL of normal saline as the same route. The results revealed that long-term administration of aspartame at high doses significantly (P < .05) reduced gonadosomatic index, serum concentration of pituitary-testicular axis hormones (FSH, LH, and testosterone). It also decreased sperm parameters and total antioxidant capacity, antioxidant enzyme activities (superoxide dismutase, catalase, and glutathione peroxidase), while it caused increase in nitric oxide and malondialdehyde levels in testis tissue and sperm samples. Also, it decreased attenuated testicular histomorphometric indices (tubular differentiation index, spermiogenesis index, and repopulation index), and steroidogenic foci, while increased mRNA damages and apoptosis rate, downregulated antiapoptotic (Bcl-2) and upregulated proapoptotic (P53, BAX, and caspase-3) mediators respectively in testis. These findings indicated that consumption of aspartame for a long period results in male reproductive toxicity by decrease in serum concentration of pituitary-testis axis hormones and induction of oxidative stress and apoptosis in testis.
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http://dx.doi.org/10.1002/tox.23028DOI Listing
February 2021

Effect of moderate-intensity exercise training on GDNF signaling pathway in testicles of rats after experimental diabetes type 1 induction.

Diabetes Res Clin Pract 2020 Sep 21;167:108332. Epub 2020 Jul 21.

Department of Exercise Physiology and Corrective Exercises, Faculty of Sport Sciences, Urmia University, Urmia, Iran.

Aims: The spermatogenesis failure is reported as the main complication for diabetes and the moderate-intensity exercise (EX) is shown to ameliorate the diabetes-induced impairments both at spermatogenesis and sperm levels. Thus, the current study was done to investigate the possible effect of EX in the sole and simultaneous form with insulin on the network between Sertoli and spermatogonial stem cells (SSCs) by focusing on niche factor Glial cell-derived neurotrophic factor (GDNF).

Methods: For this purpose, 30 mature male Wistar rats were divided into control and experimental type 1 diabetes (T1D)-induced groups. Then the T1D-induced animals were subdivided to sedentary T1D-induced (ST1D), EX + T1D, insulin (INS) + T1D and EX + INS + T1D groups. The general histological changes of testicles, mRNA and protein contents of GDNF and its special receptors gfrα1 and c-RET were evaluated and compared between groups.

Results: EX in the sole and simultaneous form with INS significantly (p < 0.05) diminished the T1D-induced histological damages, amplified the GDNF expression, and enhanced the gfrα1 and c-RET mRNA and protein contents compared to ST1D group.

Conclusion: In conclusion, the EX in the sole form promotes spermatogenesis by up-regulating the GDNF signaling system. Moreover, EX remarkably amplifies the insulin-induced ameliorative effect on spermatogenesis.
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http://dx.doi.org/10.1016/j.diabres.2020.108332DOI Listing
September 2020

Long-Term Effect of Aspartame on Male Reproductive System: Evidence for Testicular Histomorphometrics, Hsp70-2 Protein Expression and Biochemical Status.

Int J Fertil Steril 2020 Jul 15;14(2):91-101. Epub 2020 Jul 15.

Department of Comparative Histology and Embryology, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran.

Background: Aspartame is one of the most commonly consumed artificial sweeteners that is widely used in foodstuffs. There are many debatable reports about aspartame toxicity in different tissues; however, on the subject of its effects on the reproductive system, few literatures are available. The present study was carried out for evaluating effects of aspartame on the reproductive system in male mice.

Materials And Methods: In this experimental study, a total of 36 adult male mice were randomly divided into four groups of nine animals each. Three groups received aspartame at doses of 40, 80 and 160 mg/kg (gavage) for 90 days; also, a control group was considered. Twenty-four hours after the last treatment, animals were sacrificed. Then, body and testis weights, sperm parameters, serum testosterone concentration, total antioxidant capacity, and malondialdehyde (MDA) levels, antioxidant enzymes [superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px)] activities in blood, histomorphometrical indices and histochemical changes in testis were evaluated; also, mRNA and immunohistochemical expression of Hsp70-2 was measured in testis tissue.

Results: The results revealed remarkable differences in sperm parameters, testosterone and oxidative stress biomarkers levels, and histomorphometrical indices, between the control and treatment groups. Also, in 80 and 160 mg/kg aspartametreated groups, expression of Hsp70-2 was decreased. Besides, in the aspartame receiving groups, some histochemical changes in testicular tissue were observed.

Conclusion: The findings of the present study elucidated that long-term consumption of aspartame resulted in reproductive damages in male mice through induction of oxidative stress.
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http://dx.doi.org/10.22074/ijfs.2020.6065DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7382684PMC
July 2020

Experimental diabetes negatively affects the spermatogonial stem cells' self-renewal by suppressing GDNF network interactions.

Andrologia 2020 Oct 15;52(9):e13710. Epub 2020 Jun 15.

Department of Pharmacology and Toxicology, Faculty of Pharmacy, Urmia University of Medical Sciences, Urmia, Iran.

The present study was done to analyse the time-dependent effects of diabetes on Sertoli cells-spermatogonial stem cells' (SSCs) network interaction by focusing on glial cell line-derived neurotrophic factor (GDNF) and its special receptors, gfrα1 and c-RET as well as the Bcl-6b. In total, 40 Wistar rats were considered in; control, 20, 45 and 60 days diabetes-induced groups. An experimental diabetes was induced by STZ. The GDNF, gfrα1, c-RET and Bcl-6b expressions were evaluated. The serum level of testosterone, tubular repopulation (RI) and spermiogenesis (SPI) indices, general histological alterations, germ cells, mRNA damage, sperm count and viability were assessed. The diabetes, in a time-dependent manner, diminished mRNA and protein levels of GDNF, gfrα1, c-RET and Bcl-6b versus control group (p < .05), enhanced percentage of seminiferous tubules with negative RI, SPI, and diminished Leydig and Sertoli cells distribution, serum levels of testosterone, sperm count and viability. Finally, the number, percentage of cells and seminiferous tubules with normal mRNA content were significantly (p < .05) diminished. In conclusion, as a new data, we showed that the diabetes by inducing severe mRNA damage and suppressing GDNF, gfrα1, c-RET and Bcl-6b expressions, potentially affects the Sertoli-SSCs' network and consequently inhibits the SSCs' self-renewal process.
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http://dx.doi.org/10.1111/and.13710DOI Listing
October 2020

The effect of different types of exercise training on diet-induced obesity in rats, cross-talk between cell cycle proteins and apoptosis in testis.

Gene 2020 Sep 4;754:144850. Epub 2020 Jun 4.

Department of Basic Sciences, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran.

Obesity is associated with germ cell apoptosis, spermatogenesis arrest, and testicular endocrine suppression. The aim of the present study was to investigate the crosstalk between germ cell apoptosis and cell cycle machinery in sedentary and obese rats after moderate-intensity continuous (MICT), high-intensity continuous (HICT) and High-intensity interval (HIIT) exercise trainings. Male Wistar rats (n = 30) were randomly divided into 5 groups; the control, sedentary high-fat diet (HFD)-received (HFD-sole), MICT, HICT and HIIT-induced HFD-received groups. The serum levels of LDL-C, HDL-C, triglyceride, and testosterone, mRNA and protein levels of Cyclin D1, Cdk4, p21, apoptotic cell number/mm of testicular tissue and testicular DNA fragmentation ratio were investigated. The obese animals in HFD-sole group represented a significant (p < 0.05) reduction in serum HDL-C and testosterone levels, Cyclin D1, Cdk4 expressions, and exhibited a remarkable (p < 0.05) increment in LDL-C, triglyceride, p21 expression, apoptotic cell number and DNA fragmentation ratio versus control animals. However, the animals in MICT, HICT, HIIT groups exhibited a significant (p < 0.05) increment in serum HDL-C and testosterone, Cyclin D1 and Cdk4 expressions and showed a significant (p < 0.05) reduction in serum LDL-C and triglyceride, p21 expression, apoptotic cell number and DNA fragmentation versus the HFD-sole group. In conclusion, a crosslink between cell cycle machinery and apoptosis of germ cells was revealed in the testicles of HFD-sole animals, and MICT, HICT and HIIT could ameliorate the obesity-induced impairments, respectively. This effect may be attributed to the effect of exercise training protocols on maintaining Cyclin D1 and Cdk4 and suppressing p21 expression levels in the testicles.
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http://dx.doi.org/10.1016/j.gene.2020.144850DOI Listing
September 2020

Testosterone amplifies HSP70-2a, HSP90 and PCNA expression in experimental varicocele condition: Implication for DNA fragmentation.

Reprod Biol 2020 Sep 24;20(3):384-395. Epub 2020 May 24.

Department of Microbiology, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran.

The DNA fragmentation and failure in post-meiotic maturation of the spermatozoa because of testosterone withdrawal can affect the fertilization potential in varicocele (VCL) patients. To find out the exact mechanism of VCL-induced failure in histone-protamine replacement process and DNA fragmentation, the correlations between the levels of expression of HSP70-2a, HSP90, PCNA, TP1/2 and PCNA genes and the patterns of DNA methylation were investigated before and after testosterone administration in rats. In total, 40 mature male Wistar rats (10 in each group) were assigned between control (with no intervention), control-sham (undergone a simple laparotomy), VCL-induced (VCL-sole), and testosterone-treated VCL-induced (VCLT) groups. The HSP70-2a, HSP90, PCNA, TP1, and TP2 genes expressions and the patterns of global DNA methylation were determined in all groups. A statistically significant (p < 0.05) reduction were found in the HSP70-2a, HSP90, PCNA, TP1 and TP2 genes expressions in VCL-sole group. In VCLT group, testosterone was shown to significantly (p < 0.05) up-regulate the HSP70-2a, HSP90, PCNA, and TP2expression levels, but TP1 expression has not been changed. Furthermore, the VCLT group exhibited higher DNA methylation rates compared to VCL-sole animals. In conclusion, testosterone, by up-regulating the HSP70-2a and HSP90 expressions and maintaining the pre-existing HSP70-2a and HSP90 proteins levels, may be the reason for the significant increment in TP2 expression during post-meiotic stage and can boost the global methylation rates of DNA via up-regulating the PCNA expression, suggesting that administration of testosterone can mitigate the VCL-impaired histone-protamine replacement and DNA methylation rates and protect the cellular DNA content from VCL-induced oxidative stress.
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http://dx.doi.org/10.1016/j.repbio.2020.04.007DOI Listing
September 2020

Ameliorative effects of crocin on paraquat-induced oxidative stress in testis of adult mice: An experimental study.

Int J Reprod Biomed 2019 Dec 26;17(11):807-818. Epub 2019 Dec 26.

Department of Histology and Embryology, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran.

Background: Paraquat (PQ), as a pyridine compound, is widely used worldwide to control annual weeds. The oxidative stress caused by PQ can cause deleterious changes in the testicular tissue.

Objective: An investigation on the protective effects of Crocin (CCN) against PQ-induced oxidative damages and apoptotic indices in testicular tissue.

Materials And Methods: Twenty-eight adult male albino mice (20-25 gr) were divided into four groups (n = 7/each). The control group received 0.1 ml/day of normal saline by intraperitoneal injection (IP); sham-control group received PQ 5 mg/kg/day, IP, and the experimental groups received PQ (CCN+PQ) and CCN-sole (200 mg/kg/day, IP), respectively, for 35 continuous days. At the end of the treatment period, the testes were dissected out and used for biochemical, molecular, and histological analyses. The expressions of tumor suppressor , B-cell lymphoma 2 (), and were considered as hallmark factors of mitochondria-dependent apoptosis. Moreover, the testicular superoxide dismutase (SOD) and malondialdehyde (MDA) were evaluated as key biomarkers for oxidative stress.

Results: The PQ significantly (p 0.02, p 0.01) diminished the spermatogenesis indices and SOD, increased MDA levels, and enhanced the apoptosis-related gene expression. However, the co-administration of CCN and PQ significantly (p 0.01, p 0.01, p 0.02) ameliorated the spermatogenesis ratio, upregulated the SOD level as well as expression, and reduced the MDA content and apoptosis vs the PQ-sole group.

Conclusion: This study showed that the antioxidant properties of CCN enable to ameliorate the PQ-induced destructive effects by upregulating the testicular structure, antioxidant and apoptotic status.
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http://dx.doi.org/10.18502/ijrm.v17i10.5490DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6906852PMC
December 2019

Ameliorative Effect of Crocin on Sperm Parameters and In Vitro Fertilization in Mice under Oxidative Stress Induced by Paraquat.

Int J Fertil Steril 2020 Jan 11;13(4):307-314. Epub 2019 Nov 11.

Department of Histology and Embryology, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran.

Background: Paraquat (PQ) is an herbicide that is genotoxic and cytotoxic for male germ cells. In this study, we investigated the protective role of crocin (Cr) against the destructive effects of PQ on sperm quality and fertilization (IVF) outcomes.

Materials And Methods: In this experimental study, a total of 28 male mice (20-25 g) were divided into four groups: control, which received intraperitoneal (IP) injections of 0.1 ml normal saline per day; PQ group received IP injections of PQ (5 mg/kg/day); experimental (PQ+Cr group) received PQ along with IP injections of Cr (200 mg/kg/day); and positive control (Cr) received IP injections of Cr (200 mg/kg/day). In the last two weeks of the treatment period (35 days of treatment), 16 non-pregnant mice were stimulated to receive adult oocytes. At the end of the treatment period, after euthanizing the mice, the sperms were extracted from the epididymis of each mouse and prepared for evaluation of sperm parameters and IVF.

Results: In the PQ+Cr group, Cr caused a significant increase in the average number of sperms and the mean percentage of motile and viable sperms. There was a significant decrease in the mean number of immature and DNA-damaged sperms compared to the PQ group (P<0.001). IVF evaluation in the PQ+Cr group showed that the mean percentage of fertilization, two- and four-cell embryos, blastocysts, and hatched embryos significantly increased. Cr caused a significant decrease in the mean percentage of the arrested embryos compared to the PQ group (P<0.001). However, the Cr group did not have any toxic effects on sperm quality or IVF results.

Conclusion: The findings of this study showed that Cr, due to its effective and potent antioxidant properties, could reduce or suppress the destructive effects on sperm parameters and IVF caused by PQ.
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http://dx.doi.org/10.22074/ijfs.2020.5617DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6875857PMC
January 2020

Moderate-intensity exercise training ameliorates the diabetes-suppressed spermatogenesis and improves sperm parameters: Insole and simultaneous with insulin.

Andrologia 2019 Dec 23;51(11):e13457. Epub 2019 Oct 23.

Department of Physiology, Faculty of Medicine, Urmia University of Medical Sciences, Urmia, Iran.

The current study was conducted to investigate the ameliorative effect of moderate-intensity exercise training insole and simultaneous with insulin on diabetes (DM)-induced pathogenesis at the testicular tissue and sperm level. For this purpose, 36 mature male Wistar rats were divided into six groups, including sedentary control (Con), exercise training (EX), sedentary experimental DM-induced (SDM), exercise training + DM-induced (DM + EX), insulin-treated sedentary DM-induced (DM + INS) and exercise training and insulin-treated DM-induced (DM + INS + EX) groups. Following DM induction, the 6-week exercise training intervention (30 min of moderate-intensity running on a treadmill, once daily [5 days/week]) was considered in EX groups. The tubular differentiation (TDI) and spermiogenesis (SPI) indices, testicular total antioxidant capacity (TAC), superoxide dismutase (SOD) and glutathione peroxidase (GPX) contents, serum testosterone and insulin levels, the apoptosis ratio and sperm parameters were assessed. The exercise in sole (EX) and simultaneous forms with INS (DM + INS + EX group) ameliorated the DM-suppressed spermatogenesis and spermiogenesis indices, up-regulated the serum testosterone and insulin levels, enhanced testicular SOD content, inhibited the apoptosis and improved almost all sperm parameters. In conclusion, exercise training, when simultaneously considered with insulin, fairly boosts the insulin-induced impacts, including the up-regulated testicular endocrine and antioxidant status, spermatogenesis and sperm quality.
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http://dx.doi.org/10.1111/and.13457DOI Listing
December 2019

Moderate-intensity Exercise Training in Sole and Simultaneous Forms with Insulin Ameliorates the Experimental Type 1 Diabetes-induced Intrinsic Apoptosis in Testicular Tissue.

Int J Sports Med 2019 Dec 22;40(14):909-920. Epub 2019 Oct 22.

Department of Exercise Physiology and Corrective Exercises, Faculty of Sport Sciences, Urmia University, Urmia, Iran.

The aim of this study was to investigate the ameliorative effect of moderate-intensity exercise training in sole and simultaneous forms with insulin on experimental type 1 diabetes (T1D)-induced apoptosis. A total of 36 mature male Wistar rats were divided into six equally sized groups, including sedentary control (Con), moderate-intensity exercise training (E-sole), sedentary T1D-induced (D-sole), moderate-exercise-trained T1D-induced (DE), insulin-treated sedentary T1D-induced (DI) and exercise-trained, and insulin-treated T1D-induced (DEI) groups. The 6-week exercise training intervention was involved 30 min of moderate-intensity running on a treadmill once daily (5 days/week). Next, tubular differentiation (TDI) and spermiogenesis (SPI) indices were assessed. The Bcl-2, Bax and caspase-3 expressions were determined using RT-PCR, immunohistochemistry and western blot techniques. Finally, the TUNEL staining was used to analyze the apoptosis ratio. The moderate-intensity exercise training in the sole and when simultaneously considered with insulin (DEI) maintained testicular cellularity, up-regulated Bcl-2 expression, reduced Bax expression and ameliorated the diabetes-induced apoptosis. We failed to show remarkable alterations in caspase-3 mRNA and protein levels in the DE group versus D-sole animals. In conclusion, the moderate-intensity exercise training is able to potentially protect testicular cells from T1D-induced intrinsic apoptosis via up-regulating Bcl-2 and downregulating Bax expressions. Moreover, it amplifies the insulin-induced anti-apoptotic impacts.
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http://dx.doi.org/10.1055/a-0985-4332DOI Listing
December 2019

Zeta and hyaluronic acid assessments, novel sperm selection procedures, in animal model for male infertility.

Andrologia 2019 Dec 16;51(11):e13447. Epub 2019 Oct 16.

Division of Histology and Embryology, Department of Basic Science, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran.

Considering varicocele (VCL)-induced severe, progressive DNA damage, histone-protamine anomalies and low sperm production, in the current study, the experimental VCL was induced and the efficiency of hyaluronic acid (HA)-binding method (HABM) and zeta preparation procedure (ZPP) in selection of appropriate spermatozoa was compared with those spermatozoa from intact animals. Following 2 and 4 months, the histological alterations in testicular tissue, sperm count and viability were assessed to prove the VCL condition. The spermatozoa were undergone simple wash, HABM and ZPP. The chromatin condensation, active caspase-3 expression, DNA fragmentation and apoptosis index were analysed after applying selection techniques and compared with the spermatozoa from intact and VCL-induced animals, which were undergone a simple wash. Observations showed that both HABM and ZPP effectively prepared the spermatozoa with higher chromatin condensation and lower DNA damage. Meanwhile, the ZPP exerted a more preferable effect by preparing the spermatozoa with higher chromatin condensation, and lower caspase-3 expression, and DNA disintegrity versus the HABM, especially after 4 months. In conclusion, ZPP seems to exert much more reliable efficiency in selecting appropriate spermatozoa for ICSI processes, while more studies are needed to find out which one is more useful in the clinical assisted reproductive technique (ART) process.
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http://dx.doi.org/10.1111/and.13447DOI Listing
December 2019

Effects of nano-selenium on mRNA expression of markers for spermatogonial stem cells in the testis of broiler breeder males.

Vet Res Forum 2019 15;10(2):139-144. Epub 2019 Jun 15.

Department of Basic Sciences, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran.

Fertility is one of the most important parameters in breeder farms and cockerels play an outstanding role in the fertility of eggs in broiler breeder farms. Todays, supplementation of chicken diet with additives such as organic selenium is used to increase fertility. The aim of this study was to evaluate the effects of different levels of nano-selenium (Nano-Se) on the expression of molecular markers of spermatogonial stem cells (SSCs) in the testis of broiler breeder males. A total of 30 roosters of 40 weeks of age were randomly divided into five groups. Groups were as follows: 1) control (normal diet) group, 2) diet supplemented with 0.30 mg kg sodium selenite, 3) diet supplemented with 0.15 mg kg Nano-Se, 4) diet supplemented with 0.30 mg kg Nano-Se, and 5) diet supplemented with 0.60 mg kg Nano-Se. At the end of the experimental period (5 week), birds were autopsied and samples from testis of all birds were collected. The testis samples were used to examine the β1-integrin (CD29), thy-1 (CD90) and NANOG mRNA expression by real-time PCR. The results showed that testis of the groups fed with the diets supplemented with 0.60 mg kg and 0.15 mg kg of Nano-Se had the highest and lowest mRNA expression of SSCs markers, respectively. In conclusion, the present study indicated that Nano-Se had advantages over sodium selenite. Diet supplemented with 0.60 mg kg of Nano-Se may contribute to optimal fertility via increasing the mRNA expression of SSCs markers of roosters' testis and could be used to delay the reduction of fertility caused by aging in broiler breeder males.
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http://dx.doi.org/10.30466/vrf.2018.86992.2128DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6626653PMC
June 2019

Preliminary Findings of Platelet-Rich Plasma-Induced Ameliorative Effect on Polycystic Ovarian Syndrome.

Cell J 2019 Oct 15;21(3):243-252. Epub 2019 Jun 15.

Department of Basic Science, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran.Electronic

Objective: Polycystic ovarian syndrome (PCOS) is characterized by hormonal imbalance, oxidative stress and chronic anovulation. The present study was designed to assess ameliorative effect of auto-locating platelet-rich plasma (PRP), as a novel method, for inhibiting PCOS-induced pathogenesis in experimentally-induced hyperandrogenic PCOS.

Materials And Methods: In this experimental study, 30 immature (21 days old) female rats were assigned into five groups, including control (sampled after 30 days with no treatment), 15 and 30 days PCOS-sole-induced as well as 15 and 30 days PRP auto-located PCOS-induced groups. Serum levels of estrogen, progesterone, androstenedione, testosterone, follicle stimulating hormone (FSH), luteinizing hormone (LH), ovarian total antioxidant capacity (TAC), malondialdehyde (MDA), glutathione peroxidase (GSH-px) and superoxide dismutase (SOD) were evaluated. Expression of estrogen receptor α (), β () and were assessed. Finally, the numbers of intact follicles per ovary and mRNA damage ratio were analyzed.

Results: PRP groups significantly (P<0.05) decreased serum levels of FSH, LH, testosterone and androstenedione and remarkably (P<0.05) increased estrogen and progesterone syntheses versus PCOS-sole groups. The PRP auto-located animals exhibited increased TAC, GSH-px and SOD levels, while they showed diminished MDA content (P<0.05) versus PCOS-sole groups. The PRP auto-located groups exhibited an elevated expression of and versus PCOS-sole groups. Moreover, PRP groups significantly (P<0.05) decreased expression and mRNA damage compared to PCOS-sole groups, and remarkably improved follicular growth.

Conclusion: PRP is able to regulate hormonal interaction, improve the ovarian antioxidant potential as well as folliculogenesis and its auto-location could be considered as a novel method to prevent/ameliorate PCOS-induced pathogenesis.
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http://dx.doi.org/10.22074/cellj.2019.5952DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6582424PMC
October 2019

Deoxynivalenol reduces quality parameters and increases DNA damage in mice spermatozoa.

Andrologia 2019 Jun 31;51(5):e13238. Epub 2019 Jan 31.

Department of Animal Sciences, Faculty of Agriculture, Urmia University, Urmia, Iran.

This study was performed to investigate in vitro effects of deoxynivalenol (DON) on mice sperm quality parameters including viability, motility and DNA damages at various concentrations and exposure times. Mice spermatozoa were exposed to DON at 0, 2.5, 5 and 10 µM for 1, 3 and 6 hr, motility parameters were evaluated by computer-assisted analysis and viability was examined by colorimetric metabolic activity assay and HOS test. DNA damage was examined by acridine orange staining, and sperm damages via lipid peroxidation pathway were determined by malondialdehyde (MDA) content measurement. DON affected sperm parameters in a concentration- and time-dependent manner. In all test groups, the average path velocity and progressive motile spermatozoa were remarkably reduced. In comparison with the controls, after 1, 3 and 6 hr exposure to DON, viability of spermatozoa was reduced 25, 30 and 49% respectively. DON exposure at 10 µM for 6 hr resulted in 15% DNA damage and 2.5-fold more MDA generation, when compared with nonexposed spermatozoa. Our data suggest that DON causes sperm quality parameters decline in concentration- and time-dependent fashion, which attribute to the reduction in sperm metabolic activity and membrane integrity and equally to increase in lipid peroxidation rate and DNA damage.
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http://dx.doi.org/10.1111/and.13238DOI Listing
June 2019

Berberine ameliorates experimental varicocele-induced damages at testis and sperm levels; evidences for oxidative stress and inflammation.

Andrologia 2019 Mar 17;51(2):e13179. Epub 2018 Oct 17.

Gametogenesis Research Center, Kashan University of Medical Sciences, Kashan, Iran.

The present study was performed to show the ameliorative effect of berberine (BBR), as an antioxidant and anti-inflammatory agent, against experimental varicocele (VCL)-induced molecular and histological damages. For this purpose, 50 mature Wistar rats were divided into control, control-sham, VCL-sole, 50 mg/kg and 100 mg/kg BBR-treated VCL-induced groups. The tissue levels of interleukin-6 (IL-6), tumour necrosis factor-α (TNF-α), nitric oxide (NO), total antioxidant capacity (TAC), malondialdehyde (MDA), superoxide dismutase (SOD) and gluthatione peroxidase (GSH-px) as well as the mRNA levels of testicular CuZn SOD, MnSOD, EC-SOD and GSH-px were evaluated. The serum concentration of testosterone and germ cells mRNA damage were analysed. Finally, the sperm viability, motility, DNA integrity and chromatin condensation were analysed. Observations revealed that, the BBR significantly downregulated VCL-increased IL-6, TNF-α and NO levels, upregulated the CuZn SOD, MnSOD, EC-SOD and GSH-px mRNA level, decreased testicular MDA content, enhanced serum testosterone level and ameliorated testicular TAC, SOD and GSH-px levels. The animals in BBR-treated groups exhibited diminished mRNA damage versus non-treated VCL-induced group. The BBR has significantly (p < 0.05) improved sperm parameters. In conclusion, the BBR by promoting testicular antioxidant potential and by downregulating inflammatory reactions fairly promotes spermatogenesis and upregulates the sperm quality.
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http://dx.doi.org/10.1111/and.13179DOI Listing
March 2019

Silymarin amplifies apoptosis in ectopic endometrial tissue in rats with endometriosis; implication on growth factor GDNF, ERK1/2 and Bcl-6b expression.

Acta Histochem 2018 Nov 5;120(8):757-767. Epub 2018 Sep 5.

Department of Basic Sciences, Faculty of Veterinary Medicine, P.O. BOC: 1177, Urmia University, Urmia, Iran. Electronic address:

The present prospective study was done to evaluate the effect of silymarin (SMN) on endometriotic-like legions establishment and growth in experimentally-induced endometriosis. For this purpose, the experimental endometriosis was induced in 12 rats and then the animals subdivided into endometriosis-sole and SMN (50 mg kg, orally)+endometriosis groups. Following 28 days, the legions establishment, size, Glial cell line-derived neurotrophic factor (GDNF), gfrα1, B Cell Lymphoma 6 (Bcl-6b), Bcl-2, extracellular regulator kinase (ERK1/2) expression ratios, angiogenesis, the apoptosis and fibrosis indices were investigated. The SMN significantly (P < 0.05) decreased the enometriotic-like legions establishment and size, decreased mRNA levels of GDNF, gfrα1, Bcl-6b and Bcl-2 and remarkably diminished GDNF, gfrα1, Bcl-6b and Bcl-2-positive cells distribution/mm of tissue versus endometriosis-sole group. The SMN + endometriosis group exhibited a significant (P < 0.05) enhancement in ERK1/2 expression and represented diminished vascularized area and increased apoptosis and fibrosis indices, as well. In conclusion, the SMN by down-regulating GDNF and its receptor gfrα1 expression inhibits GDNF-gfrα1 complex generation and consequently suppresses Bcl-6b expression. Moreover, the SMN by enhancing the ERK1/2 expression and by suppressing the Bcl-2 expression promotes the apoptosis pathway. Finally, the SMN by down-regulating the angiogenesis ratio accelerates apoptosis and consequently induces severe fibrosis in endometriotic-like legions.
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http://dx.doi.org/10.1016/j.acthis.2018.08.003DOI Listing
November 2018

The effect of vitamin C on mice hemolytic anemia induced by phenylhydrazine: an animal model study using histological changes in testis, pre-implantation embryo development, and biochemical changes.

Iran J Basic Med Sci 2018 Jul;21(7):668-677

Department of Anatomy & Embryology, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran.

Objectives: The aim of the present study was to assess the effects of vitamin C (Vit C) on hemolytic anemia induced by phenylhydrazine (PHZ).

Materials And Methods: Twenty-four healthy male mice were divided into four groups, randomly: Control group (0.1 ml/day, normal slaine, IP), PHZ group that received only PHZ 8 mg/100 g/48 hr, IP, PHZ+Vit C group that received PHZ 8 mg/100 g/48 hr, IP and Vit C 100 mg/kg BW-1/day by gavage and Vit C group that received 100 mg/kg BW-1/day Vit C by gavage. After 35 days, germinal cells, RNA damage, sperm parameters, testis malondialdehyde (MDA) content, serum total antioxidant capacity (TAC), pre-implantation embryo development and mRNA levels of cyclin D1 and c-myc in two-cell, and morula and blastocyst stages were assessed.

Results: Vit C reduced the RNA damage, enhanced sperm quality, promoted pre-implantation embryo development and improved testicular antioxidant and endocrine status (<0.05). Vit C reduced cyclin D1 expression and up-regulated c-myc mRNA level in two-cell, morula, and blastocyst embryonic cells.

Conclusion: Vit C enhanced the fertilizing potential by ameliorating the endocrine status, antioxidant capacity, and sperm quality. Finally, the cyclin D1 and c-myc gene expressions were regulated in PHZ+Vit C treated group that promoted the embryo development.
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http://dx.doi.org/10.22038/IJBMS.2018.25819.6356DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6098957PMC
July 2018

Aflatoxin B1 impairs spermatogenesis: An experimental study for crosslink between oxidative stress and mitochondria-dependent apoptosis.

Environ Toxicol 2018 Nov 20;33(11):1204-1213. Epub 2018 Aug 20.

Department of Biology, Faculty of Basic Science, Urmia University, Urmia, Iran.

The present experimental study was carried out to investigate the crosslink between aflatoxin B1 (AFB1)-induced oxidative stress and mitochondria-dependent apoptosis in testicles. For this purpose, 24 mature male Swiss albino mice were randomly divided into control and test groups. The AFB1 was dissolved in corn oil and ethanol (95:5, v/v) vehicle. The animals in test group subdivided into three groups, which received the AFB1 at a daily dose of 20 μg/kg body weight, through intraperitoneal (i.p.) route, for 7, 14, and 21 days. The mice in the control group received the vehicle alone for 21 days. The expression of Bcl-2, Bax, p53, and caspase-3 at both mRNA and protein levels were analyzed by using reverse transcription PCR (RT-PCR) and immunohistochemistry, respectively. Moreover, the mitochondrial content of germinal epithelium, tubular differentiation (TDI), and spermiogenesis (SPI) indices was analyzed. Finally, the apoptosis was assessed by using TUNEL staining. Observations revealed that the AFB1 remarkably (P < .05) reduced Bcl-2 expression at both mRNA and protein levels. Up-regulated Bax, caspase-3, and p53 expression were revealed in AFB1-received animals, which developed time-dependently. Histological examinations exhibited a significant reduction in TDI and SPI indices. Finally, the AFB1-induced apoptosis index increased time-dependently. In conclusion, the AFB1 adversely affects the spermatogenesis via inducing oxidative stress, diminishing cellular mitochondrial content and enhancing pro-apoptotic Bax, caspase-3, and p53 expression. All these impairments result in mitochondria-dependent apoptosis.
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http://dx.doi.org/10.1002/tox.22627DOI Listing
November 2018

Fennel induces cytotoxic effects against testicular germ cells in mice; evidences for suppressed pre-implantation embryo development.

Environ Toxicol 2018 May 15. Epub 2018 May 15.

Department of Basic Science, Faculty of Veterinary, Urmia University, Urmia, Iran.

Foeniculum vulgare (FVE; fennel) is an aromatic plant belonging to Umbelliferae family, which is widely used in traditional societies because of its different pharmaceutical properties. To uncover the fennel-derived essential oil (FVEO)-induced effects on male reproductive potential, 24 mature male albino mice were divided into, control, 0.37, 0.75, and 1.5 mg kg FVEO-received groups. Following 35 days, the animals were euthanized and the testicular tissue and sperm samples were collected. The histological alterations, tubular differentiation (TDI), spermiogenesis (SPI) indices, apoptosis ratio, and RNA damage of germinal cells were analyzed. Moreover, the sperm count, motility, viability, chromatin condensation, and DNA fragmentation were assessed. Finally, the pre-implantation embryo development including; the percentage of zygote, 2-cell embryos and blastocysts were assessed. Observations showed that the FVEO, dose dependently, increased histological damages, resulted in germ cells dissociation, depletion, nuclear shrinkage and significantly (P < .05) decreased tubular differentiation and spermiogenesis ratios. Moreover, the FVEO-received animals (more significantly in 1.5 mg kg -received group) exhibited decreased sperm count, viability, and motility and represented enhanced percentage of sperms with decondensed chromatin and DNA fragmentation. Finally, the animals in FVEO-received group showed diminished zygote formation and represented decreased pre-implantation embryo development compared to control animals. In conclusion, our data showed that, FVEO albeit at higher doses, is able to adversely affect cellular DNA and RNA contents, which in turn is able to negatively affect the sperm count and morphology. All these impairments are able to negatively affect the fertilization potential as well as pre-implantation embryo development.
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http://dx.doi.org/10.1002/tox.22570DOI Listing
May 2018

Effect of (R)-(+) Pulegone on Ovarian Tissue; Correlation with Expression of Aromatase Cyp19 and Ovarian Selected Genes in Mice.

Cell J 2018 Jul 18;20(2):231-243. Epub 2018 Mar 18.

Department of Basic Sciences, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran.

Objectives: Pulegone (PGN) is a monoterpene ketone, whose metabolites exert several cytotoxic effects in various tissues. The present study was conducted in order to evaluate the (R)-(+) PGN-induced alterations in ovarian aromatization, proto-oncogenes and estrogen receptorα ( ERα) and ERβ receptors expressions.

Materials And Methods: In this experimental study, mature albino mice were divided into experimental (received 25 mg/kg, 50 mg/kg and 100 mg/kg PGN, orally for 35 days) and control (received 2% solution of Tween 80 as a PGN solvent, orally) groups. The mRNA levels of Erα, Erβ, p53, Bcl-2, and cytochrome p450 (Cyp19) as well as ovarian angiogenesis were analyzed through reverse transcription polymerase chain reaction and immunohistochemical techniques, respectively. Moreover, apoptosis of follicular cells, serum estrogen and progesterone levels and mRNA damage were investigated via using terminal transferase and biotin-16-dUTP staining, electrochemilunescence and fluorescent microscopy methods, respectively.

Results: The PGN reduced Erα, Erβ and Cyp19 expression at 50 mg/kg and 100 mg/kg doses, while significantly elevating p53 and reducing Bcl-2 expression. Finally, PGN impaired ovarian angiogenesis, increased apoptosis, elevated follicular atresia and reduced serum levels of estrogen and progesterone.

Conclusions: Chronic exposure to PGN (50 mg/kg and 100 mg/kg), severely affects ovarian aromatization, protooncogenes mRNA levels and expression of ERs.
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http://dx.doi.org/10.22074/cellj.2018.4798DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5893295PMC
July 2018

Silymarin and celecoxib ameliorate experimental varicocele-induced pathogenesis: evidences for oxidative stress and inflammation inhibition.

Int Urol Nephrol 2018 Jun 5;50(6):1039-1052. Epub 2018 Apr 5.

Division of Histology and Embryology, Department of Basic Science, Faculty of Veterinary Medicine, Urmia University, P.O. Box: 1177, Urmia, Iran.

Background: The present study was done to investigate the ameliorative effect of silymarin (SMN) and celecoxib (CEL) on varicocele (VCL)-induced detrimental impact in testicular tissue.

Methods: Mature Wistar rats were divided into control and test groups. Following VCL induction, the animals in test group were subdivided into non-treated VCL-induced, SMN-treated (50 mg/kg, orally), CEL-treated (10 mg/kg) and SMN + CEL-treated groups. Following 60 days, testicular total antioxidant capacity (TAC), malondialdehyde (MDA), nitric oxide (NO), superoxide dismutase (SOD), glutathione peroxidase (GSH-px), total thiol molecules (TTM), mRNA and protein levels of COX2 and mRNA level of iNos were analyzed. Moreover, the germinal cells apoptosis and mRNA damage were examined.

Results: Observations revealed that co-administration of SMN and CEL significantly (P < 0.05) up-regulated TAC, SOD, GSH-px and TTM levels and resulted in a remarkable (P < 0.05) reduction in iNos and COX2 expression, NO and MDA contents. The animals in SMN + CEL-treated group exhibited significantly (P < 0.05) lower number of apoptotic cells and cells with mRNA damage per one mm.

Conclusion: The SMN by up-regulating testicular TAC, SOD, GSH-px and TTM levels and the CEL by inhibiting COX2 and iNos expression as well as NO content could fairly ameliorate the VCL-decreased spermatogenesis.
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http://dx.doi.org/10.1007/s11255-018-1862-5DOI Listing
June 2018