Il-1� C376a transversion variant and risk of idiopathic male infertility in Iranian men: A genetic association study

Background: IL-1α produced by Sertoli cells is considered to act as a growth factor for spermatogonia. In this study, we investigated the association of the C376A polymorphism in IL-1α with male infertility in men referring to the Kashan IVF Center. Materials and Methods: In this case-control study, 2 ml of blood was collected from 230 fertile and 230 infertile men. After DNA extraction, the C376A variant was genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). In addition, the molecular effects of the C376A transversion were analysed using bioinformatics tools. Results: A significant association was observed between the homozygous genotype CC with male infertility [odds ratio (OR)=1.97, 95% confidence interval (CI)=1.14-3.41, P=0.016)]. Carriers of C (AC+CC) showed a similar risk for male infertility (OR=1.78, 95% CI=1.06-2.99, P=0.030). Also, allelic analysis showed that the C allele is associated with male infertility (OR=1.43, 95% CI=1.09-1.88, P=0.011). In sub-group analysis, we found that the AC genotype is associated with asthenozoospermia (OR=2.38, 95% CI=1.03-5.53, P=0.043). In addition, carriers of C were at high risk for asthenozoospermia (OR=2.25, 95% CI=1.01-4.10, P=0.047). Also, C allele was significantly associated with oligozoospermia (OR=1.44, 95% CI=1.01-2.06, P=0.049) and non-obstructive azoospermia (OR=1.67, 95% CI =1.04-2.68, P=0.034). Finally, in silico analysis showed that the C376A polymorphism could alter splicing especially in the acceptor site. Conclusion: This is the preliminary report on the association of IL-1α C376A polymorphism with male infertility in the Kashan population. This association shows that the IL-1α gene may be a biomarker for male infertility, and therefore needs additional investigations in future studies to validate this. Keywords: Genetic Polymorphism, Interleukin-1α, Male Infertility, Spermatogenesi

Association of C3953T transition in interleukin 1β gene with idiopathic male infertility in an Iranian population

In this study we investigate the association of C3953T transition single nucleotide polymorphism in the fifth exon of the interleukin 1β gene with idiopathic male infertility. In a case-control study, blood samples were collected from 230 fertile and 207 infertile men who referred to the Kashan IVF centre. Genotypes of samples at the C3953T location were determined by polymerase chain reaction-restriction fragment length polymorphism. The data showed a significant association of TT genotype (OR = 2.49, 95CI = 1.02�6.10; p = 0.0452) and T allele (OR = 1.46, 95CI = 1.07�1.99; p = 0.0174) with male infertility. In a subgroup analysis, we found that the TT genotype (OR = 3.28, 95CI = 1.16�9.26; p = 0.0249) and T allele (OR = 1.63, 95CI = 1.10�2.41; p = 0.0142) were associated with oligozoospermia. Our findings suggest that the C3953T polymorphism could be considered as a potential biomarker for a genetic diagnosis of male infertility. © 2017, © 2017 The British Fertility Society

The protective effect of bone marrow mesenchymal stem cells in a rat model of ischemic stroke via reducing the C-Jun N-terminal kinase expression

Ischemic stroke is the main cause of disability and mortality worldwide. Apoptosis and inflammation have an important role in ischemic brain injury. Mesenchymal stem cells (MSCs) have protective effects on stroke treatment due to anti-inflammatory properties. The inhibition of the C-Jun N-terminal kinase (JNK) pathway may be one of the molecular mechanisms of the neuroprotective effect of MSCs in ischemic brain injury. Twenty-eight male Wistar rats were divided randomly into 3 groups. Except the sham group, others subjected to transient middle cerebral artery occlusion (tMCAO). Bone marrow MSCs or saline were injected 3 h after tMCAO. Sensorimotor behavioral tests were performed 24 and 72 h after ischemia and reperfusion (I/R). The rats were sacrificed 72 h after I/R and infarct volume was measured by TTC staining. The number of apoptotic neurons and astrocytes in the peri-infarct area was assessed by TUNEL assay. The morphology of cells was checked by Nissl staining, and the expression of p-JNK was detected by immunohistochemistry and Western blot. Behavioral scores were improved and infarct volume was reduced by MSCs 24 h and 72 h after tMCAO. TUNEL assay showed that neuronal apoptosis and astroglial activity in the penumbra region were reduced by MSCs. Also, Nissl staining showed lower neuronal apoptosis in BMSCs-treated rats compared to controls. JNK phosphorylation which was profoundly induced by ischemia was significantly decreased after MSCs treatment. We concluded that anti-apoptotic and anti-inflammatory effects of MSCs therapy after brain ischemia may be associated with the down-regulation of p-JNK. © 2019 Elsevier Gmb

Lipoprotein lipase gene polymorphisms as risk factors for stroke: A computational and meta-analysis

Abstract Objective(s): Stroke is the most common neurological disorder and genetic susceptibility has an important role in its etiology. Polymorphism in several genes such as lipoprotein lipase (LPL) is propounded as a risk for stroke. This meta-analysis investigated the association of rs285 and rs320 LPL polymorphism with stroke risk. Materials and Methods: We searched PubMed, Clarivate Analytics Web of Science, Google Scholar, and Science Direct databases for appropriate studies. The odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to estimate the strength of this association. Also, the effects of four common polymorphisms (rs268, rs285, rs320, and rs328) on the molecular aspects of LPL were evaluated by in silico tools. Five studies were included in meta-analysis after screening. Results: Our data indicated that rs320 significantly decreased the risk of stroke (G vs. T: OR= 0.64, 95%CI=0.54-0.76; GG vs. TT: OR=0.47, 95%CI=0.29-0.75; TG vs. TT: OR=0.65, 95%CI=0.53-0.80; TG+GG vs. TT: OR=0.62, 95%CI=0.51-0.75; GG vs. TT+TG: OR=0.51, 95%CI=0.32-0.82). Moreover, a significant association between rs285 and diminution of stroke risk was seen (P- vs. P+: OR=0.72, 95%CI=0.58-0.91; P-P- vs. P+P+: OR=0.50, 95%CI=0.31-0.82; P+P-+P-P- vs. P+P+: OR=0.72, 95%CI=0.53-0.96; P-P- vs. P+P++P+P-: OR=0.581, 95%CI=0.369-0.916). Also, the same results were observed after stratifying, without any publication bias (PEgger>0.05). Furthermore, computational analysis revealed that rs268 and rs328 may affect the protein structure (prediction: non-neutral; score=19; expected accuracy=59%) while rs320 could affect the RNA structure (distance=0.2264, P-value=0.0534; P<0.2 is significant). Conclusion: This meta-analysis indicated that risk of stroke was decreased in rs320 and rs285 polymorphisms in the LPL gene. Key Words: Computational biology, Genetic polymorphism, Lipoprotein lipase, Meta-analysis, Strok

The regulatory role of Toll-like receptors after ischemic stroke: neurosteroids as TLR modulators with the focus on TLR2/4

Ischemic stroke is the most common cerebrovascular disease and considered as a worldwide leading cause of death. After cerebral ischemia, different pathophysiological processes including neuroinflammation, invasion and aggregation of inflammatory cells and up-regulation of cytokines occur simultaneously. In this respect, Toll-like receptors (TLRs) are the first identified important mediators for the activation of the innate immune system and are widely expressed in glial cells and neurons following brain trauma. TLRs are also able to interact with endogenous and exogenous molecules released during ischemia and can increase tissue damage. Particularly, TLR2 and TLR4 activate different downstream inflammatory signaling pathways. In addition, TLR signaling can alternatively play a role for endogenous neuroprotection. In this review, the gene and protein structures, common genetic polymorphisms of TLR2 and TLR4, TLR-related molecular pathways and their putative role after ischemic stroke are delineated. Furthermore, the relationship between neurosteroids and TLRs as neuroprotective mechanism is highlighted in the context of brain ischemia. © 2018, Springer Nature Switzerland AG

Prenatal urban traffic noise exposure impairs spatial learning and memory and reduces glucocorticoid receptor expression in the hippocampus of male rat offspring

Introduction: Exposure to noise stress during early life may permanently affect the structure and function of the central nervous system. The aim of this study was to evaluate the effects of prenatal exposure to urban traffic noise on the spatial learning and memory of the rats' offspring and the expression of glucocorticoid receptors (GRs) in their hippocampi. Methods: Three g\roups of pregnant rats were exposed to recorded urban traffic noise for 1, 2 or 4 h/day during the last week of pregnancy. At the age of 45 days, their male offspring were introduced to the Morris water maze (MWM) for assessment of spatial learning and memory. The corticosterone levels were measured in the offspring's sera by radioimmunoassay, and the relative expression of glucocorticoid and mineralocorticoid receptors (MRs) in their hippocampi was evaluated via RT-PCR. Results: Facing urban traffic noise for 2 and 4 h/day during the third trimester of pregnancy caused the offspring to spend more time and to travel a larger distance than the controls to find the target platform. Analogously, these two groups were inferior to their control counterparts in the probe test. Also, prenatal noise stress elevated the corticosterone concentration in the sera of the rats' offspring and dose-dependently decreased the relative expression of the mRNA of both GRs and MRs in their hippocampi. Conclusions: Urban traffic noise exposure during the last trimester of pregnancy impairs spatial learning and memory of rat offspring and reduces GRs and MRs gene expression in the hippocampus

Prenatal urban traffic noise exposure impairs spatial learning and memory and reduces glucocorticoid receptor expression in the hippocampus of male rat offspring

Introduction: Exposure to noise stress during early life may permanently affect the structure and function of the central nervous system. The aim of this study was to evaluate the effects of prenatal exposure to urban traffic noise on the spatial learning and memory of the rats' offspring and the expression of glucocorticoid receptors (GRs) in their hippocampi. Methods: Three g\roups of pregnant rats were exposed to recorded urban traffic noise for 1, 2 or 4 h/day during the last week of pregnancy. At the age of 45 days, their male offspring were introduced to the Morris water maze (MWM) for assessment of spatial learning and memory. The corticosterone levels were measured in the offspring's sera by radioimmunoassay, and the relative expression of glucocorticoid and mineralocorticoid receptors (MRs) in their hippocampi was evaluated via RT-PCR. Results: Facing urban traffic noise for 2 and 4 h/day during the third trimester of pregnancy caused the offspring to spend more time and to travel a larger distance than the controls to find the target platform. Analogously, these two groups were inferior to their control counterparts in the probe test. Also, prenatal noise stress elevated the corticosterone concentration in the sera of the rats' offspring and dose-dependently decreased the relative expression of the mRNA of both GRs and MRs in their hippocampi. Conclusions: Urban traffic noise exposure during the last trimester of pregnancy impairs spatial learning and memory of rat offspring and reduces GRs and MRs gene expression in the hippocampus

Neuroprotective Effects of Oxytocin Hormone after an Experimental Stroke Model and the Possible Role of Calpain-1

Background Different mechanisms will be activated during ischemic stroke. Calpain proteases play a pivotal role in neuronal death after ischemia damage through apoptosis. Anti-apoptotic activities of the oxytocin (OT) in different ischemic tissues were reported in previous studies. Recently, a limited number of studies have noted the protective effects of OT in the brain. In the present study, the neuroprotective potential of OT in an animal model of transient middle cerebral artery occlusion (tMCAO) and the possible role of calpain-1 in the penumbra region were assessed. Methods Adult male Wistar rats underwent 1 hour of tMCAO and were treated with nasal administration of OT. After 24 hours of reperfusion, infarct size was evaluated by triphenyltetrazolium chloride. Immunohistochemical staining and Western blotting were used to examine the expression of calpain-1. Nissl staining was performed for brain tissue morphology evaluation. Results OT reduced the infarct volume of the cerebral cortex and striatum compared with the ischemia control group significantly (P < .05). Calpain-1 overexpression, which was caused by ischemia, decreased after OT administration (P < .05). The number of pyknotic nuclei in neurons increased dramatically in the ischemic area and OT attenuated the apoptosis of neurons in the penumbra region (P < .01). Conclusion We provided evidence for the neuroprotective role of OT after tMCAO through calpain-1 attenuation. Key Words Stroke tMCAO calpain-1 oxytoci

Postnatal development and sensory experience synergistically underlie the excitatory/inhibitory features of hippocampal neural circuits: Glutamatergic and GABAergic neurotransmission

During a postnatal critical period balance of excitation/inhibition in the developing brain is highly regulated by environmental signals. Compared to the visual cortex, rare document includes effects of sensory experience on the hippocampus, which is also bombarded by sensory signals. In this study, basic and tetanized field excitatory postsynaptic potentials (fEPSPs) were recorded in CA1 area of hippocampus of light-(LR) and dark-reared (DR) rats (at 2, 4 and 6 weeks of age). Also, we assessed age- and activity-dependent changes in the N-Methyl- d-aspartic acid (NMDA) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors subunit compositions and, GABA producing enzymes. While the sensory deprivation increased amplitude of baseline fEPSPs, it decreased degree of potentiation of post-tetanus responses. Expression of GluA1 and GluA2 subunits of AMPA receptors was increased across age in DR rats. In contrast to LR rats, mRNA and protein expression of GluN1, GluN2A and GluN2B subunits of NMDA receptors was decreased in DR ones. Also, dark rearing diminished expression of GABA synthesis enzymes GAD65 and GAD67. These results indicate that, sensory experience adjusts synaptic plasticity and might also affect the balance of excitation/inhibition in the hippocampus. © 2016 IBRO

Evaluating effects of visual deprivation during critical period of brain development on expression of NMDA receptor subunits in rats hippocampus

Background and purpose: Visual deprivation during critical period of brain development impairs structure and function of NMDA receptors in visual cortex. Parts of visual signals go to the hippocampus through the visual cortex. Therefore, this study aimed at investigating the effects of visual deprivation during critical period of brain development on NMDA receptor subunits expression in rats hippocampus. Materials and methods: This experimental study was carried out in 36 male rats that were divided into two groups. They were kept in standard 12 hour light/dark condition (Light Reared-LR) or in complete darkness (Dark Reared-DR) from birth to the time of experiments. The animals in each group were divided into 3 groups and studied at the ages of 2, 4 and 6 weeks. Expression of mRNA of NR1, NR2A and NR2B subunits in hippocampus was evaluated by RT-PCR using Western Blot technique. The protein expression of those subunits was also investigated.Results: Relative expression of mRNA and protein of NR1 and NR2A subunits increased time dependently in LR animals, but the expression of NR2B subunit did not change. Although dark rearing did not prevent increasing of NR1 expression, but reduced the expression of NR2A and NR2B subunits.Conclusion: Visual deprivation during critical period of brain development time dependently inhibited maturation of NMDA receptor of rat�s hippocampus. © 2015, J Mazandaran Univ Med Sci. All rights reserved