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Papers by Amir m Fattahi

Epithelial-mesenchymal transition process during embryo implantation

Cell and Tissue Research

Middle East Fertility Society Journal, 2021

Oxidative stress has an undeniable role in the impairment of sperm function and idiopathic male i... more Oxidative stress has an undeniable role in the impairment of sperm function and idiopathic male infertility. On the other hand, the local antioxidant system particularly glutathione peroxidase 3 (GPX3) as an extracellular enzyme protects male fertility from oxidative damages. Therefore, in the current study, we evaluated the association between two functional polymorphisms of the GPX3 gene with its levels in seminal fluid and subsequently with the risk of male infertility. We recruited 100 fertile and 100 infertile men for the study. Our results showed that the concentration of GPX3 was higher in the fertile group than infertile patients (p= <0.01), and there were positive correlations between GPX3 concentration in seminal fluid with sperm motility and morphology. The frequency of rs8177404 and rs3828599 genotypes and alleles was significantly different between the groups and we found that having the rs8177404 polymorphism (TC and CC genotypes) could increase the risk of idiopath...

Endocrine Connections

Embryo implantation is a complex process in which multiple molecules acting together under strict... more 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 cross-talk 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.

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

Systems Biology in Reproductive Medicine

ABSTRACT miRNAs are involved in different biological processes, including proliferation, differen... more ABSTRACT 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-β: transforming growth factor-beta.

Biomedical Human Kinetics

Study aim: In this study, we evaluated the effects of acute and chronic exercise on the plasma FA... more Study aim: In this study, we evaluated the effects of acute and chronic exercise on the plasma FAs and their association with cardiac hypertrophy indices. Material and methods: In this pilot study, 15 sedentary and 15 athlete women underwent acute and long-term water aerobic exercise and their plasma FA levels and a number of electrocardiographic parameters, such as left ventricular end-diastolic diameter index (LVEDDI), left ventricular ejection fraction (LVEF), left ventricular mass index (LVMI), and wall thickness were evaluated before and after the exercise program. Results: The acute exercise significantly increased palmitic and oleic acid levels in non-athletes and stearic acid in both groups. However, the same type of exercise decreased linoleic acid only in non-athlete women (p < 0.05). The water aerobics training caused a significant decrease in the levels of palmitic, stearic, and arachidonic acid, SFA/UFA, and ω3/ ω6 ratios and also an increase in α-Linolenic acid and ...

An update on platelet-rich plasma (PRP) therapy in endometrium and ovary related infertilities: clinical and molecular aspects

Systems Biology in Reproductive Medicine

ABSTRACT Administration of platelet-rich plasma (PRP) is one of the well-recommended strategies f... more ABSTRACT Administration of platelet-rich plasma (PRP) is one of the well-recommended strategies for the treatment of endometrium- and ovary-associated infertility. Due to the autologous source of PRP, minimal risks for disease transmission and immunogenic and allergic responses are expected in this method. Despite the extensive use of PRP in medicine, its precise mechanism of action in endometrial and ovarian tissues is still unknown. Nevertheless, the induction of cell proliferation, chemotaxis, regeneration, extracellular matrix synthesis, remodeling, angiogenesis, and epithelialization are the main pathways for PRP to affect female reproductive organs. Given the promising results of previous studies, it is necessary to standardize PRP preparation protocols for different therapeutic purposes and also clearly determine appropriate inclusion and exclusion criteria for recruiting patients. In the current review, we presented a summary of studies on PRP therapy for endometrium- and ovary-associated infertility with a focus on the possible mechanisms by which PRP enhances endometrial receptivity and regenerates ovarian function. Abbreviations: PRP: platelet-rich plasma; ART: assisted reproductive technology; POF: premature ovarian failure; TGF: transforming growth factors; PDGF: platelet-derived growth factors; IGF-I: insulin-like growth factor-1; HGF: hepatocyte growth factor; EGF: epidermal growth factor; FGF: fibroblast growth factor; VEGF: vascular endothelial growth factor; ADP: adenosine diphosphate, ATP: adenosine triphosphate; PDGF: platelet-derived growth factor; COX2: cyclooxygenase-2; TP53: tumor protein 53; ER-α: estrogen receptors alpha; ER-β: estrogen receptors beta; PR: progesterone receptor; RIF: recurrent implantation failure; G-CSF: granulocyte colony-stimulating factor; iNOS: inducible nitric oxide synthase; NF-kβ: nuclear factor kappa beta; MMPs: matrix metalloproteinases; Col1a1: collagen type I alpha 1; IL: interleukin; FSH: follicle-stimulating hormone; AMH: anti-Mullerian hormone; GDF-9: growth differentiation factor 9.

Journal of Assisted Reproduction and Genetics

Embryo implantation is accompanied by a potent inflammatory response, and a gradient of cytokines... more Embryo implantation is accompanied by a potent inflammatory response, and a gradient of cytokines and chemokines produced by endometrial cells supports the embryo-endometrial interaction. C-reactive protein (CRP) serves as an early marker of inflammation and recent studies have illustrated that controlled ovarian hyperstimulation (COH) could increase its levels. Interestingly, a high chance of pregnancy has been reported in women who had an elevated CRP level on the day of embryo transfer. It seems an elevated systemic inflammation in the in vitro fertilization (IVF) cycle can increase the implantation and pregnancy rates. However, the results regarding the association of CRP with ART outcomes are controversial. Therefore, in this review, we aimed to describe how CRP levels change during a cycle of IVF treatment and which factors can potentially affect this pattern of change. Furthermore, the association of CRP with ART outcomes has been discussed.

Exosome‐based intercellular communication in female reproductive microenvironments

Journal of Cellular Physiology

Different strategies are applied for cellular cross‐talk and organization in multicellular organi... more Different strategies are applied for cellular cross‐talk and organization in multicellular organisms. Exosomes are a homogenous population of biological nanoparticles (30–100 nm), originated from multivesicular bodies. The exosomes (Exos) could regulate and affect both cellular physiology and pathophysiology in various organs, such as the female reproductive tract, by altering gene pathways and/or epigenetic programming. Besides, engineered Exos have the potential to be used as a novel drug and gene delivery tools. Here in this review, we discussed various aspects of exosome‐based intercellular communication in female reproductive microenvironments. Furthermore, we addressed the findings and issues related to Exos in reproductive biology to give a better view of the involved molecular mechanisms. Moreover, clinical applications of the Exos and their isolation source/methods have been considered to throw some light on the progression of new biological, diagnostic, and therapeutic approaches in clinical embryology.

Geburtshilfe und Frauenheilkunde

Introduction Adrenomedullin 2 (ADM2) and vascular endothelial growth factor (VEGF) affect ovarian... more Introduction Adrenomedullin 2 (ADM2) and vascular endothelial growth factor (VEGF) affect ovarian function, especially angiogenesis and follicular development. The actions of VEGF can be antagonized by its soluble receptors, soluble Fms-like tyrosine kinase-1 (sFlt-1) and soluble VEGF receptor 2 (sVEGFR-2), as they decrease its free form. In the present study, we evaluated the relationship between follicular fluid (FF) levels of AMD2, VEGF and its soluble receptors, and ICSI outcomes. Materials and Methods ICSI cycle outcomes were evaluated and FF levels of VEGF, sFlt-1, sVEGFR-2 and ADM2 were determined using ELISA kits. Results FF levels of ADM2, VEGF, and sVEGFR-2 were significantly higher in non-responders compared to other ovarian response groups (p < 0.05). There were significant correlations between ADM2, VEGF and sVEGFR-2 levels as well as VEGF/sFlt-1 and VEGF/sVEGFR-2 ratios (r = 0.586, 0.482, 0.260, and − 0.366, respectively). Based on the ROC curve, the cutoff value fo...

Lymphocytes immunotherapy for preserving pregnancy: Mechanisms and Challenges

American Journal of Reproductive Immunology

Due to the expression of paternal antigens by the embryo, pregnancy is considered as a semi‐allog... more Due to the expression of paternal antigens by the embryo, pregnancy is considered as a semi‐allograft and so immunological dysregulation is considered as one of the important causes in repeated implantation failure (RIF) and recurrent pregnancy loss (RPL). It has been revealed that lymphocytes immunotherapy (LIT) could be an appropriate approach to prevent pregnancy loss in such patients. Various mechanisms have been suggested for effectiveness of LIT such as enhancing expression of anti‐paternal cytotoxic antibodies (APCA), progesterone‐induced blocking factor (PIBF), anti‐idiotypic antibodies (Ab2), and mixed lymphocyte reaction blocking antibodies (MLR‐Bf), as well as reduction in the T helper 1/T helper 2 ratio and deviation in the pattern of cytokines production. However, there are controversial results about the beneficial effect of LIT treatment in RIF and RPL patients. In the current study, we reviewed findings of LIT in RIF and RPL patients with a focus on possible mechanisms of alloimmunization in preserving pregnancy. Besides, we highlighted possible reasons for mixed results about the effectiveness of LIT and way of solving the problem. Also, we proposed potential laboratory and clinical criteria to recruit patients for LIT.

N1-methylnicotinamide (MNAM) as a guardian of cardiovascular system

Journal of cellular physiology, 2018

Atherosclerosis is identified as the formation of atherosclerotic plaques, which could initiate t... more Atherosclerosis is identified as the formation of atherosclerotic plaques, which could initiate the formation of a blood clot in which its growth to coronary artery can lead to a heart attack. N-methyltransferase (NNMT) is an enzyme that converts the NAM (nicotinamide) to its methylated form, N1-methylnicotinamide (MNAM). Higher levels of MNAM have been reported in cases with coronary artery disease (CAD). Further, MNAM increases endothelial prostacyclin (PGI2) and nitric oxide (NO) and thereby causes vasorelaxation. The vasoprotective, anti-inflammatory and anti-thrombotic roles of MNAM have been well documented; however, the exact underlying mechanisms remain to be clarified. Due to potential role of MNAM in the formation of lipid droplets (LDs), it might exert its function in coordination with lipids, and their targets. In this study, we summarized the roles of MNAM in cardiovascular system and highlighted its possible mode of actions.

SIRT3-mediated cardiac remodeling/repair following myocardial infarction

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, Jan 15, 2018

The recent investigations have extensively focused on the importance of sirtuins, as a highly con... more The recent investigations have extensively focused on the importance of sirtuins, as a highly conserved family of gene products, particularly SIRT3 in various biological and pathological processes. SIRT3, the mitochondrial NAD+-dependent deacetylase has been demonstrated to target a broad range of proteins involved in the oxidative stress, ischemia-reperfusion injury, mitochondrial metabolism homeostasis and cellular death. The critical function of SIRT3 in myocardial infarction (MI), which is one of the complex phenotype of coronary artery disease and a result of interaction between various genetic and environmental factors, as well as in cardiac repair and remodeling post-MI have attracted more attention in the recent years. Therefore, in this review, we will summarize important literature about the involvement of SIRT3 in cardiac remodeling/repair following MI and its potential underlying mechanisms.

Dental research journal

The aim of this study was to assess for the first time the effects of different amounts of ethano... more The aim of this study was to assess for the first time the effects of different amounts of ethanol solvent on the microtensile bond strength of composite bonded to dentin using a polyhedral oligomeric silsesquioxane (POSS)-incorporated adhesive. This experimental study was performed on 120 specimens divided into six groups (in accordance with the ISO TR11405 standard requiring at least 15 specimens per group). Occlusal dentin of thirty human molar teeth was exposed by removing its enamel. Five teeth were assigned to each of six groups and were converted to 20 microtensile rods (with square cross-sections of 1 mm × 1 mm) per group. The "Prime and Bond NT" (as a common commercial adhesive) was used as the control group. Experimental acrylate-based bonding agents containing 10 wt% POSS were produced with five concentrations of ethanol as solvent (0, 20, 31, 39, and 46 wt%). After application of adhesives on dentin surface, composite cylinders (height = 6 mm) were bonded to de...

European journal of medical research, Jan 25, 2017

Little information is available concerning antioxidant effects of plant teas (water boiled) which... more Little information is available concerning antioxidant effects of plant teas (water boiled) which are used more commonly in traditional Chinese medicine than other extracts. Thus, we addressed this issue by evaluating the ability of teas from four different plants with therapeutic potential on gynecological diseases. The aqueous extracts of Semen persicae, Leonurus cardiaca, Hedyotis diffusa, and Curcuma zedoaria rhizome were prepared and then their effects on copper-induced low-density lipoprotein cholesterol (LDL-C) oxidation were evaluated by spectrophotometric method. Density gradient ultracentrifugation method was recruited to isolate LDL-C from healthy individuals. Our results showed that adding 10, 20, and 30 µl S. persicae could increase the lag phase duration of LDL-C oxidation compared with control reaction 12, 21, and 33%, respectively. The most effective delay (87%) was observed when 30 µl H. diffusa was added to the reaction. In cases of L. cardiaca and C. zedoaria, we ...

Journal of cardiovascular and thoracic research, 2017

Introduction: Atherosclerosis could be deemed as a chronic, progressive, and inflammatory disease... more Introduction: Atherosclerosis could be deemed as a chronic, progressive, and inflammatory disease. It has been well-documented that high-density lipoprotein (HDL) can reduce the risk of the atherosclerosis occurrence through exerting some anti-atherogenic mechanisms. In recent years, the strong evidence has suggested that paraoxonase 1 (PON1) may contribute to antioxidant properties of HDL. In the present study, the impact of a diet enriched with cholesterol and also the PON1 inhibition on atheroma formation and lipid profile has been investigated. Methods: In this study, 24 New Zealand rabbits were randomly assigned to three groups receiving standard diet, atherogenic diet, and atherogenic diet plus once daily intramuscular injection of nandrolone decanoate as the PON1 inhibitor. Triglyceride, cholesterol, HDL, and low-density lipoprotein (LDL) were determined and both cholesterol accumulation in aorta and fatty streak formation were evaluated. Results: The comparison of the result...

Theriogenology, Jan 29, 2017

Since fatty acid composition of uterus phospholipids is likely to influence embryo implantation, ... more Since fatty acid composition of uterus phospholipids is likely to influence embryo implantation, this study was conducted to investigate the effects of dietary omega-3 and -6 fatty acids on implantation rate as well as uterine phospholipid fatty acids composition during mice pre-implantation period. Sixty female mice were randomly distributed into:1) control (standard pellet), 2) omega-3 (standard pellet + 10% w/w of omega-3 fatty acids) and 3) omega-6 (standard pellet + 10% w/w of omega-6 fatty acids). Uterine phospholipid fatty acid composition during the pre-implantation window (days 1-5 of pregnancy) was analyzed using gas-chromatography. The implantation rate on the fifth day of pregnancy was also determined. Our results showed that on days 1, 2 and 3 of pregnancy, the levels of arachidonic acid (ARA) as well as total omega-6 fatty acids were significantly higher and the levels of linolenic acid and total omega-3 fatty acids were statistically lower in the omega-6 group compare...

Systems biology in reproductive medicine, Jan 9, 2017

Sperm DNA damage is one of the associated factors of idiopathic male infertility and abnormal spe... more Sperm DNA damage is one of the associated factors of idiopathic male infertility and abnormal spermatogenesis. This study was conducted to assess possible association between risk of male infertility with X-ray repair cross complementing group 1 (XRCC1) Arg399Gln (G to A) and DNA ligase 4 (LIG4) Thr9Ile (C to T) gene polymorphisms which are involved in different DNA repair pathways. In this case-control study 191 fertile and 191 infertile men (29-40 years old) were enrolled. The single-nucleotide polymorphism genotypes and alleles of XRCC1 Arg399Gln and LIG4 Thr9Ile were assessed using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. There was no significant association between XRCC1 Arg399Gln polymorphism and risk of male infertility. The frequency of LIG4 Thr9Ile genotypes and alleles were statistically different between fertile and infertile men (p<0.001). We found that the CT genotype increased infertility risk more than threefold (...

Molecular Reproduction and Development

Considering the self-renewal and differentiation ability of pluripotent stem cells, some studies ... more Considering the self-renewal and differentiation ability of pluripotent stem cells, some studies have pointed out the possibility of stem cell-derived sperm production. Most studies that test this hypothesis have been conducted on rodents, with some promising results; however, studies on humans are progressing slowly, and have encountered technical and ethical hurdles. Established methods to differentiate stem cells-including embryoid bodies, co-culturing, and various feeder cells-may provide a niche that is similar to in vivo conditions and resolve epigenetic abnormalities, but a gonadal-like three-dimensional structure is still required to produce germ cells with the correct imprinting. In the last few years, sperm-like cells with fertilizing capacity were produced from mouse embryonic stem cells, and the resulting embryos from these cells yielded live offspring. Future research should move towards the use of adult stem cells, however, owing to the unavailability of embryonic cells in adults. More intensive research and techniques are required since in vitro spermatogenesis provides hope to individuals without mature sperm who cannot be treated, and may be a useful system to study the precise mechanism of spermatogenesis. In this review, we describe recent studies of in vitro spermatogenesis mechanisms and related techniques in mammals. We also discuss the possible cell surface markers and culture conditions that might improve in vitro spermatogenesis. K E Y W O R D S gametogenesis, germ cell differentiation, in-vitro derived gametes, spermatogenesis, stem cell [The] possibility of obtaining patient-specific sperm, derived from stem cells, has drawn much attention in recent years. 1 | INTRODUCTION About 10-15% of all couples are infertile, with male infertility accounting for half of these cases (Gu, Liu, & Belmonte, 2012, Massart, Lissens, Tournaye, & Stouffs, 2012). About 200,000 babies are born every year using assisted reproductive technologies, which has helped many couples with fertility problems (Zegers-Hochschild et al., 2009); unfortunately, patients without gametes cannot benefit from the existing approaches. For example, normal sperm collection in 10% of infertile men with obstructive azoospermia and non-obstructive azoospermia is not possible-especially in non-obstructive azoospermia patients, for whom even testicular extraction of sperm is not helpful (Su et al., 1999). Other causes of male infertility are associated with impaired spermatogenesis due to genetic deficiency or environmental factors, or result from cancer treatments, including

Gynecological Endocrinology

Placental growth factor (PlGF) is an angiogenic factor which belongs to vascular endothelial grow... more Placental growth factor (PlGF) is an angiogenic factor which belongs to vascular endothelial growth factor (VEGF) family. In addition to the angiogenic function of PlGF, in some conditions such as preeclampsia and early pregnancy losses, it can induce inflammatory reactions which could be accompanied with reduced angiogenesis. Hence, it is crucial to investigate inflammatory and angiogenic switching states and understand underlying mechanisms. PlGF is expressed in endometrium, placenta and trophoblast cells and is involved in maturation of uterine NK cells. Up-regulation of PlGF directs VEGF to VEGFR-2 and reinforces angiogenesis. However, when VEGF/VEGFR-2 signaling pathway is impaired, PlGF may shift to severe inflammation and cause tissue damages which could lead to early pregnancy losses. Downregulation of PlGF has also been reported in pregnancy complications. In this review, we discussed the role of PlGF in embryo implantation failure and early pregnancy loss and also possible mechanisms regarding the role of PlGF in angiogenic/inflammatory switching in early pregnancy losses. Furthermore, we summarized the effects of various compounds on PlGF expression and briefly talked about its therapeutic potential that may be an opportunity for prevention of pregnancy loss.

Journal of cardiovascular and thoracic research, 2017

Introduction: Considering importance of fatty acids in developing coronary artery disease (CAD) a... more Introduction: Considering importance of fatty acids in developing coronary artery disease (CAD) and lack of information about saphenous vein which is commonly used as coronary arterial bypass, in this study we investigated differences in fatty acids composition between saphenous vein and aorta tissues in patients with CAD. Methods: Biopsy samples of aortic tissues and saphenous veins as well as blood samples were obtained form 42 patients with CAD. Fatty acids composition of the tissues was determined using gas chromatography and also serum lipid profile was evaluated by commercial kits. Results: Levels of palmitic acid (16:0) were significantly higher in aorta in compared with saphenous (P < 0.001). Also levels of most unsaturated fatty acids (16:1, 18:1n-9, 18:1t, 18:2t, 18:3 n-9 and 22:3n-3) were statistically higher in saphenous tissue than aorta tissue (P < 0.05). Mean levels of linoleic acid (18:2 n-6) was higher in aorta tissue in comparison with saphenous tissue (P = 0...

Epithelial-mesenchymal transition process during embryo implantation

Cell and Tissue Research

Middle East Fertility Society Journal, 2021

Oxidative stress has an undeniable role in the impairment of sperm function and idiopathic male i... more Oxidative stress has an undeniable role in the impairment of sperm function and idiopathic male infertility. On the other hand, the local antioxidant system particularly glutathione peroxidase 3 (GPX3) as an extracellular enzyme protects male fertility from oxidative damages. Therefore, in the current study, we evaluated the association between two functional polymorphisms of the GPX3 gene with its levels in seminal fluid and subsequently with the risk of male infertility. We recruited 100 fertile and 100 infertile men for the study. Our results showed that the concentration of GPX3 was higher in the fertile group than infertile patients (p= <0.01), and there were positive correlations between GPX3 concentration in seminal fluid with sperm motility and morphology. The frequency of rs8177404 and rs3828599 genotypes and alleles was significantly different between the groups and we found that having the rs8177404 polymorphism (TC and CC genotypes) could increase the risk of idiopath...

Endocrine Connections

Embryo implantation is a complex process in which multiple molecules acting together under strict... more 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 cross-talk 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.

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

Systems Biology in Reproductive Medicine

ABSTRACT miRNAs are involved in different biological processes, including proliferation, differen... more ABSTRACT 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-β: transforming growth factor-beta.

Biomedical Human Kinetics

Study aim: In this study, we evaluated the effects of acute and chronic exercise on the plasma FA... more Study aim: In this study, we evaluated the effects of acute and chronic exercise on the plasma FAs and their association with cardiac hypertrophy indices. Material and methods: In this pilot study, 15 sedentary and 15 athlete women underwent acute and long-term water aerobic exercise and their plasma FA levels and a number of electrocardiographic parameters, such as left ventricular end-diastolic diameter index (LVEDDI), left ventricular ejection fraction (LVEF), left ventricular mass index (LVMI), and wall thickness were evaluated before and after the exercise program. Results: The acute exercise significantly increased palmitic and oleic acid levels in non-athletes and stearic acid in both groups. However, the same type of exercise decreased linoleic acid only in non-athlete women (p < 0.05). The water aerobics training caused a significant decrease in the levels of palmitic, stearic, and arachidonic acid, SFA/UFA, and ω3/ ω6 ratios and also an increase in α-Linolenic acid and ...

An update on platelet-rich plasma (PRP) therapy in endometrium and ovary related infertilities: clinical and molecular aspects

Systems Biology in Reproductive Medicine

ABSTRACT Administration of platelet-rich plasma (PRP) is one of the well-recommended strategies f... more ABSTRACT Administration of platelet-rich plasma (PRP) is one of the well-recommended strategies for the treatment of endometrium- and ovary-associated infertility. Due to the autologous source of PRP, minimal risks for disease transmission and immunogenic and allergic responses are expected in this method. Despite the extensive use of PRP in medicine, its precise mechanism of action in endometrial and ovarian tissues is still unknown. Nevertheless, the induction of cell proliferation, chemotaxis, regeneration, extracellular matrix synthesis, remodeling, angiogenesis, and epithelialization are the main pathways for PRP to affect female reproductive organs. Given the promising results of previous studies, it is necessary to standardize PRP preparation protocols for different therapeutic purposes and also clearly determine appropriate inclusion and exclusion criteria for recruiting patients. In the current review, we presented a summary of studies on PRP therapy for endometrium- and ovary-associated infertility with a focus on the possible mechanisms by which PRP enhances endometrial receptivity and regenerates ovarian function. Abbreviations: PRP: platelet-rich plasma; ART: assisted reproductive technology; POF: premature ovarian failure; TGF: transforming growth factors; PDGF: platelet-derived growth factors; IGF-I: insulin-like growth factor-1; HGF: hepatocyte growth factor; EGF: epidermal growth factor; FGF: fibroblast growth factor; VEGF: vascular endothelial growth factor; ADP: adenosine diphosphate, ATP: adenosine triphosphate; PDGF: platelet-derived growth factor; COX2: cyclooxygenase-2; TP53: tumor protein 53; ER-α: estrogen receptors alpha; ER-β: estrogen receptors beta; PR: progesterone receptor; RIF: recurrent implantation failure; G-CSF: granulocyte colony-stimulating factor; iNOS: inducible nitric oxide synthase; NF-kβ: nuclear factor kappa beta; MMPs: matrix metalloproteinases; Col1a1: collagen type I alpha 1; IL: interleukin; FSH: follicle-stimulating hormone; AMH: anti-Mullerian hormone; GDF-9: growth differentiation factor 9.

Journal of Assisted Reproduction and Genetics

Embryo implantation is accompanied by a potent inflammatory response, and a gradient of cytokines... more Embryo implantation is accompanied by a potent inflammatory response, and a gradient of cytokines and chemokines produced by endometrial cells supports the embryo-endometrial interaction. C-reactive protein (CRP) serves as an early marker of inflammation and recent studies have illustrated that controlled ovarian hyperstimulation (COH) could increase its levels. Interestingly, a high chance of pregnancy has been reported in women who had an elevated CRP level on the day of embryo transfer. It seems an elevated systemic inflammation in the in vitro fertilization (IVF) cycle can increase the implantation and pregnancy rates. However, the results regarding the association of CRP with ART outcomes are controversial. Therefore, in this review, we aimed to describe how CRP levels change during a cycle of IVF treatment and which factors can potentially affect this pattern of change. Furthermore, the association of CRP with ART outcomes has been discussed.

Exosome‐based intercellular communication in female reproductive microenvironments

Journal of Cellular Physiology

Different strategies are applied for cellular cross‐talk and organization in multicellular organi... more Different strategies are applied for cellular cross‐talk and organization in multicellular organisms. Exosomes are a homogenous population of biological nanoparticles (30–100 nm), originated from multivesicular bodies. The exosomes (Exos) could regulate and affect both cellular physiology and pathophysiology in various organs, such as the female reproductive tract, by altering gene pathways and/or epigenetic programming. Besides, engineered Exos have the potential to be used as a novel drug and gene delivery tools. Here in this review, we discussed various aspects of exosome‐based intercellular communication in female reproductive microenvironments. Furthermore, we addressed the findings and issues related to Exos in reproductive biology to give a better view of the involved molecular mechanisms. Moreover, clinical applications of the Exos and their isolation source/methods have been considered to throw some light on the progression of new biological, diagnostic, and therapeutic approaches in clinical embryology.

Geburtshilfe und Frauenheilkunde

Introduction Adrenomedullin 2 (ADM2) and vascular endothelial growth factor (VEGF) affect ovarian... more Introduction Adrenomedullin 2 (ADM2) and vascular endothelial growth factor (VEGF) affect ovarian function, especially angiogenesis and follicular development. The actions of VEGF can be antagonized by its soluble receptors, soluble Fms-like tyrosine kinase-1 (sFlt-1) and soluble VEGF receptor 2 (sVEGFR-2), as they decrease its free form. In the present study, we evaluated the relationship between follicular fluid (FF) levels of AMD2, VEGF and its soluble receptors, and ICSI outcomes. Materials and Methods ICSI cycle outcomes were evaluated and FF levels of VEGF, sFlt-1, sVEGFR-2 and ADM2 were determined using ELISA kits. Results FF levels of ADM2, VEGF, and sVEGFR-2 were significantly higher in non-responders compared to other ovarian response groups (p < 0.05). There were significant correlations between ADM2, VEGF and sVEGFR-2 levels as well as VEGF/sFlt-1 and VEGF/sVEGFR-2 ratios (r = 0.586, 0.482, 0.260, and − 0.366, respectively). Based on the ROC curve, the cutoff value fo...

Lymphocytes immunotherapy for preserving pregnancy: Mechanisms and Challenges

American Journal of Reproductive Immunology

Due to the expression of paternal antigens by the embryo, pregnancy is considered as a semi‐allog... more Due to the expression of paternal antigens by the embryo, pregnancy is considered as a semi‐allograft and so immunological dysregulation is considered as one of the important causes in repeated implantation failure (RIF) and recurrent pregnancy loss (RPL). It has been revealed that lymphocytes immunotherapy (LIT) could be an appropriate approach to prevent pregnancy loss in such patients. Various mechanisms have been suggested for effectiveness of LIT such as enhancing expression of anti‐paternal cytotoxic antibodies (APCA), progesterone‐induced blocking factor (PIBF), anti‐idiotypic antibodies (Ab2), and mixed lymphocyte reaction blocking antibodies (MLR‐Bf), as well as reduction in the T helper 1/T helper 2 ratio and deviation in the pattern of cytokines production. However, there are controversial results about the beneficial effect of LIT treatment in RIF and RPL patients. In the current study, we reviewed findings of LIT in RIF and RPL patients with a focus on possible mechanisms of alloimmunization in preserving pregnancy. Besides, we highlighted possible reasons for mixed results about the effectiveness of LIT and way of solving the problem. Also, we proposed potential laboratory and clinical criteria to recruit patients for LIT.

N1-methylnicotinamide (MNAM) as a guardian of cardiovascular system

Journal of cellular physiology, 2018

Atherosclerosis is identified as the formation of atherosclerotic plaques, which could initiate t... more Atherosclerosis is identified as the formation of atherosclerotic plaques, which could initiate the formation of a blood clot in which its growth to coronary artery can lead to a heart attack. N-methyltransferase (NNMT) is an enzyme that converts the NAM (nicotinamide) to its methylated form, N1-methylnicotinamide (MNAM). Higher levels of MNAM have been reported in cases with coronary artery disease (CAD). Further, MNAM increases endothelial prostacyclin (PGI2) and nitric oxide (NO) and thereby causes vasorelaxation. The vasoprotective, anti-inflammatory and anti-thrombotic roles of MNAM have been well documented; however, the exact underlying mechanisms remain to be clarified. Due to potential role of MNAM in the formation of lipid droplets (LDs), it might exert its function in coordination with lipids, and their targets. In this study, we summarized the roles of MNAM in cardiovascular system and highlighted its possible mode of actions.

SIRT3-mediated cardiac remodeling/repair following myocardial infarction

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, Jan 15, 2018

The recent investigations have extensively focused on the importance of sirtuins, as a highly con... more The recent investigations have extensively focused on the importance of sirtuins, as a highly conserved family of gene products, particularly SIRT3 in various biological and pathological processes. SIRT3, the mitochondrial NAD+-dependent deacetylase has been demonstrated to target a broad range of proteins involved in the oxidative stress, ischemia-reperfusion injury, mitochondrial metabolism homeostasis and cellular death. The critical function of SIRT3 in myocardial infarction (MI), which is one of the complex phenotype of coronary artery disease and a result of interaction between various genetic and environmental factors, as well as in cardiac repair and remodeling post-MI have attracted more attention in the recent years. Therefore, in this review, we will summarize important literature about the involvement of SIRT3 in cardiac remodeling/repair following MI and its potential underlying mechanisms.

Dental research journal

The aim of this study was to assess for the first time the effects of different amounts of ethano... more The aim of this study was to assess for the first time the effects of different amounts of ethanol solvent on the microtensile bond strength of composite bonded to dentin using a polyhedral oligomeric silsesquioxane (POSS)-incorporated adhesive. This experimental study was performed on 120 specimens divided into six groups (in accordance with the ISO TR11405 standard requiring at least 15 specimens per group). Occlusal dentin of thirty human molar teeth was exposed by removing its enamel. Five teeth were assigned to each of six groups and were converted to 20 microtensile rods (with square cross-sections of 1 mm × 1 mm) per group. The "Prime and Bond NT" (as a common commercial adhesive) was used as the control group. Experimental acrylate-based bonding agents containing 10 wt% POSS were produced with five concentrations of ethanol as solvent (0, 20, 31, 39, and 46 wt%). After application of adhesives on dentin surface, composite cylinders (height = 6 mm) were bonded to de...

European journal of medical research, Jan 25, 2017

Little information is available concerning antioxidant effects of plant teas (water boiled) which... more Little information is available concerning antioxidant effects of plant teas (water boiled) which are used more commonly in traditional Chinese medicine than other extracts. Thus, we addressed this issue by evaluating the ability of teas from four different plants with therapeutic potential on gynecological diseases. The aqueous extracts of Semen persicae, Leonurus cardiaca, Hedyotis diffusa, and Curcuma zedoaria rhizome were prepared and then their effects on copper-induced low-density lipoprotein cholesterol (LDL-C) oxidation were evaluated by spectrophotometric method. Density gradient ultracentrifugation method was recruited to isolate LDL-C from healthy individuals. Our results showed that adding 10, 20, and 30 µl S. persicae could increase the lag phase duration of LDL-C oxidation compared with control reaction 12, 21, and 33%, respectively. The most effective delay (87%) was observed when 30 µl H. diffusa was added to the reaction. In cases of L. cardiaca and C. zedoaria, we ...

Journal of cardiovascular and thoracic research, 2017

Introduction: Atherosclerosis could be deemed as a chronic, progressive, and inflammatory disease... more Introduction: Atherosclerosis could be deemed as a chronic, progressive, and inflammatory disease. It has been well-documented that high-density lipoprotein (HDL) can reduce the risk of the atherosclerosis occurrence through exerting some anti-atherogenic mechanisms. In recent years, the strong evidence has suggested that paraoxonase 1 (PON1) may contribute to antioxidant properties of HDL. In the present study, the impact of a diet enriched with cholesterol and also the PON1 inhibition on atheroma formation and lipid profile has been investigated. Methods: In this study, 24 New Zealand rabbits were randomly assigned to three groups receiving standard diet, atherogenic diet, and atherogenic diet plus once daily intramuscular injection of nandrolone decanoate as the PON1 inhibitor. Triglyceride, cholesterol, HDL, and low-density lipoprotein (LDL) were determined and both cholesterol accumulation in aorta and fatty streak formation were evaluated. Results: The comparison of the result...

Theriogenology, Jan 29, 2017

Since fatty acid composition of uterus phospholipids is likely to influence embryo implantation, ... more Since fatty acid composition of uterus phospholipids is likely to influence embryo implantation, this study was conducted to investigate the effects of dietary omega-3 and -6 fatty acids on implantation rate as well as uterine phospholipid fatty acids composition during mice pre-implantation period. Sixty female mice were randomly distributed into:1) control (standard pellet), 2) omega-3 (standard pellet + 10% w/w of omega-3 fatty acids) and 3) omega-6 (standard pellet + 10% w/w of omega-6 fatty acids). Uterine phospholipid fatty acid composition during the pre-implantation window (days 1-5 of pregnancy) was analyzed using gas-chromatography. The implantation rate on the fifth day of pregnancy was also determined. Our results showed that on days 1, 2 and 3 of pregnancy, the levels of arachidonic acid (ARA) as well as total omega-6 fatty acids were significantly higher and the levels of linolenic acid and total omega-3 fatty acids were statistically lower in the omega-6 group compare...

Systems biology in reproductive medicine, Jan 9, 2017

Sperm DNA damage is one of the associated factors of idiopathic male infertility and abnormal spe... more Sperm DNA damage is one of the associated factors of idiopathic male infertility and abnormal spermatogenesis. This study was conducted to assess possible association between risk of male infertility with X-ray repair cross complementing group 1 (XRCC1) Arg399Gln (G to A) and DNA ligase 4 (LIG4) Thr9Ile (C to T) gene polymorphisms which are involved in different DNA repair pathways. In this case-control study 191 fertile and 191 infertile men (29-40 years old) were enrolled. The single-nucleotide polymorphism genotypes and alleles of XRCC1 Arg399Gln and LIG4 Thr9Ile were assessed using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. There was no significant association between XRCC1 Arg399Gln polymorphism and risk of male infertility. The frequency of LIG4 Thr9Ile genotypes and alleles were statistically different between fertile and infertile men (p<0.001). We found that the CT genotype increased infertility risk more than threefold (...

Molecular Reproduction and Development

Considering the self-renewal and differentiation ability of pluripotent stem cells, some studies ... more Considering the self-renewal and differentiation ability of pluripotent stem cells, some studies have pointed out the possibility of stem cell-derived sperm production. Most studies that test this hypothesis have been conducted on rodents, with some promising results; however, studies on humans are progressing slowly, and have encountered technical and ethical hurdles. Established methods to differentiate stem cells-including embryoid bodies, co-culturing, and various feeder cells-may provide a niche that is similar to in vivo conditions and resolve epigenetic abnormalities, but a gonadal-like three-dimensional structure is still required to produce germ cells with the correct imprinting. In the last few years, sperm-like cells with fertilizing capacity were produced from mouse embryonic stem cells, and the resulting embryos from these cells yielded live offspring. Future research should move towards the use of adult stem cells, however, owing to the unavailability of embryonic cells in adults. More intensive research and techniques are required since in vitro spermatogenesis provides hope to individuals without mature sperm who cannot be treated, and may be a useful system to study the precise mechanism of spermatogenesis. In this review, we describe recent studies of in vitro spermatogenesis mechanisms and related techniques in mammals. We also discuss the possible cell surface markers and culture conditions that might improve in vitro spermatogenesis. K E Y W O R D S gametogenesis, germ cell differentiation, in-vitro derived gametes, spermatogenesis, stem cell [The] possibility of obtaining patient-specific sperm, derived from stem cells, has drawn much attention in recent years. 1 | INTRODUCTION About 10-15% of all couples are infertile, with male infertility accounting for half of these cases (Gu, Liu, & Belmonte, 2012, Massart, Lissens, Tournaye, & Stouffs, 2012). About 200,000 babies are born every year using assisted reproductive technologies, which has helped many couples with fertility problems (Zegers-Hochschild et al., 2009); unfortunately, patients without gametes cannot benefit from the existing approaches. For example, normal sperm collection in 10% of infertile men with obstructive azoospermia and non-obstructive azoospermia is not possible-especially in non-obstructive azoospermia patients, for whom even testicular extraction of sperm is not helpful (Su et al., 1999). Other causes of male infertility are associated with impaired spermatogenesis due to genetic deficiency or environmental factors, or result from cancer treatments, including

Gynecological Endocrinology

Placental growth factor (PlGF) is an angiogenic factor which belongs to vascular endothelial grow... more Placental growth factor (PlGF) is an angiogenic factor which belongs to vascular endothelial growth factor (VEGF) family. In addition to the angiogenic function of PlGF, in some conditions such as preeclampsia and early pregnancy losses, it can induce inflammatory reactions which could be accompanied with reduced angiogenesis. Hence, it is crucial to investigate inflammatory and angiogenic switching states and understand underlying mechanisms. PlGF is expressed in endometrium, placenta and trophoblast cells and is involved in maturation of uterine NK cells. Up-regulation of PlGF directs VEGF to VEGFR-2 and reinforces angiogenesis. However, when VEGF/VEGFR-2 signaling pathway is impaired, PlGF may shift to severe inflammation and cause tissue damages which could lead to early pregnancy losses. Downregulation of PlGF has also been reported in pregnancy complications. In this review, we discussed the role of PlGF in embryo implantation failure and early pregnancy loss and also possible mechanisms regarding the role of PlGF in angiogenic/inflammatory switching in early pregnancy losses. Furthermore, we summarized the effects of various compounds on PlGF expression and briefly talked about its therapeutic potential that may be an opportunity for prevention of pregnancy loss.

Journal of cardiovascular and thoracic research, 2017

Introduction: Considering importance of fatty acids in developing coronary artery disease (CAD) a... more Introduction: Considering importance of fatty acids in developing coronary artery disease (CAD) and lack of information about saphenous vein which is commonly used as coronary arterial bypass, in this study we investigated differences in fatty acids composition between saphenous vein and aorta tissues in patients with CAD. Methods: Biopsy samples of aortic tissues and saphenous veins as well as blood samples were obtained form 42 patients with CAD. Fatty acids composition of the tissues was determined using gas chromatography and also serum lipid profile was evaluated by commercial kits. Results: Levels of palmitic acid (16:0) were significantly higher in aorta in compared with saphenous (P < 0.001). Also levels of most unsaturated fatty acids (16:1, 18:1n-9, 18:1t, 18:2t, 18:3 n-9 and 22:3n-3) were statistically higher in saphenous tissue than aorta tissue (P < 0.05). Mean levels of linoleic acid (18:2 n-6) was higher in aorta tissue in comparison with saphenous tissue (P = 0...