scholarly journals Role of antimicrobial peptide DEFB126 mutation in pathogenesis of male idiopathic infertility

2021 ◽  
Vol 23 (5) ◽  
pp. 1115-1124
Author(s):  
E. M. Khasanova ◽  
L. V. Gankovskaya ◽  
V. V. Burmakina
Keyword(s):  
Gene Expression ◽  
Male Infertility ◽  
Sperm Motility ◽  
Mutant Allele ◽  
Reproductive Tract ◽  
Control Group ◽  
Idiopathic Infertility ◽  
Fold Reduction ◽  
Distribution Frequency

Male infertility is a multifactorial disease, and elucidation of etiopathogenetic mechanisms of its progression is a topical issue. High percentage of the “idiopathic infertility” diagnosis is largely cased by inability to establish etiology of decrease in reproductive spermatic function. Mutation of в-defensin DEFB126 gene is supposed to affect the fertilizing ability of spermatozoa at different levels: it may decrease their ability to migrate through the cervical mucus and reduce binding capacity to epithelial layer of upper female reproductive tract, and it may also increase susceptibility for infections of reproductive tract, due to impairment of local protective function of defensins. Thus, the aim of the present study was to examine possible role of rs11468374 gene polymorphism of the DEFB126 gene in pathogenesis of male idiopathic infertility. Patients and methods: The group of patient with decreased fertility included 54 male subjects, ages 34 to 42, with a control group of 19 ejaculate donors without acute or chronic disease aged 28 to 36. The indicators of sperm motility in the Moscow population were compared with individual levels of DEFB126 gene expression, as well as with estimated distribution frequency of rs11468374 alleles and genotypes among the subjects.As compared with the control group, the infertile patients exhibited a more than seven-fold reduction of DEFB126 gene expression. Analysis of distribution frequency for alleles and genotypes rs11468374 polymorphic marker of the DEFB126 gene revealed that the mutant allele is detected almost twice as often in males with infertility, as compared with control group. No cases with the DEFB126 del/del genotype were found among the control group, in contrary to 16.1% in the group of patients. The patients with DEFB126 del/del genotype exhibited 5.2-fold reduction of sperm motility. Thus, the data obtained may be used to extend our knowledge on the pathogenetic mechanisms of male idiopathic infertility and to improve techniques for its diagnostics, as well as to provide personalized approach to the treatment of male reproductive disorders. The association between carriage of del mutant allele and decreased level of sperm motility suggests a role of this polymorphism in pathogenesis of male infertility. A general decrease in the level of DEFB126 gene expression in the patients affected by infertility also presumes a contribution of defensin 126 to pathogenesis of the disorder.

The Effect of PDE5 Inhibitors on the Male Reproductive Tract

2020 ◽  
Vol 26 ◽  
Author(s):  
Nikolaos Sofikitis ◽  
Aris Kaltsas ◽  
Fotios Dimitriadis ◽  
Jens Rassweiler ◽  
Nikolaos Grivas ◽  
...  
Keyword(s):  
Male Infertility ◽  
Reproductive Tract ◽  
Tunica Albuginea ◽  
Scientific Data ◽  
Secretory Function ◽  
Pde5 Inhibitors ◽  
Male Reproductive Tract ◽  
Review Study ◽  
Phosphodiesterase 5

The therapeutic range of cyclic nucleotide phosphodiesterase 5 inhibitors (PDE5) inhibitors is getting wider in the last years. This review study focuses on the potential employment of PDE5 inhibitors as an adjunct tool for the therapeutic management of male infertility. The literature tends to suggest a beneficial effect of PDE5 inhibitors on Leydig and Sertoli cells secretory function. It also appears that PDE5 inhibitors play a role in the regulation of the contractility of the testicular tunica albuginea and the epididymis. Moreover scientific data suggest that PDE5 inhibitors enhance the prostatic secretory function leading to an improvement in sperm motility. Other studies additionally demonstrate a role of PDE5 inhibitors in the regulation of sperm capacitation process. Placebo-controlled, randomized, blind studies are necessary to unambiguously incorporate PDE5 inhibitors as an adjunct tool for the pharmaceutical treatment of semen disorders and male infertility.

scholarly journals FERMT3 mediates cigarette smoke-induced epithelial–mesenchymal transition through Wnt/β-catenin signaling

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Xiaoshan Su ◽  
Junjie Chen ◽  
Xiaoping Lin ◽  
Xiaoyang Chen ◽  
Zhixing Zhu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Lung Cancer ◽  
Cell Cycle ◽  
Cell Migration ◽  
Cigarette Smoke ◽  
Epithelial Mesenchymal Transition ◽  
Control Group ◽  
Data Set ◽  
Mesenchymal Transition

Abstract Background Cigarette smoking is a major risk factor for chronic obstructive pulmonary disease (COPD) and lung cancer. Epithelial–mesenchymal transition (EMT) is an essential pathophysiological process in COPD and plays an important role in airway remodeling, fibrosis, and malignant transformation of COPD. Previous studies have indicated FERMT3 is downregulated and plays a tumor-suppressive role in lung cancer. However, the role of FERMT3 in COPD, including EMT, has not yet been investigated. Methods The present study aimed to explore the potential role of FERMT3 in COPD and its underlying molecular mechanisms. Three GEO datasets were utilized to analyse FERMT3 gene expression profiles in COPD. We then established EMT animal models and cell models through cigarette smoke (CS) or cigarette smoke extract (CSE) exposure to detect the expression of FERMT3 and EMT markers. RT-PCR, western blot, immunohistochemical, cell migration, and cell cycle were employed to investigate the potential regulatory effect of FERMT3 in CSE-induced EMT. Results Based on Gene Expression Omnibus (GEO) data set analysis, FERMT3 expression in bronchoalveolar lavage fluid was lower in COPD smokers than in non-smokers or smokers. Moreover, FERMT3 expression was significantly down-regulated in lung tissues of COPD GOLD 4 patients compared with the control group. Cigarette smoke exposure reduced the FERMT3 expression and induces EMT both in vivo and in vitro. The results showed that overexpression of FERMT3 could inhibit EMT induced by CSE in A549 cells. Furthermore, the CSE-induced cell migration and cell cycle progression were reversed by FERMT3 overexpression. Mechanistically, our study showed that overexpression of FERMT3 inhibited CSE-induced EMT through the Wnt/β-catenin signaling. Conclusions In summary, these data suggest FERMT3 regulates cigarette smoke-induced epithelial–mesenchymal transition through Wnt/β-catenin signaling. These findings indicated that FERMT3 was correlated with the development of COPD and may serve as a potential target for both COPD and lung cancer.

Cide-A Gene Expression in Patients with Obesity Qualified for Endovascular Treatment of Abdominal Aorta Aneurysm

2015 ◽  
Vol 86 (10) ◽  
Author(s):  
Marcin Feldo ◽  
Janusz Kocki ◽  
Jan Feldo ◽  
Sylwia Łukasik ◽  
Jacek Bogucki ◽  
...  
Keyword(s):  
Gene Expression ◽  
Endovascular Aneurysm Repair ◽  
The Body ◽  
Control Group ◽  
Study Group ◽  
Aorta Aneurysm ◽  
Group Play ◽  
Aneurysm Repair ◽  
Adipose Tissue Cells

Abstractgene and the genes of LRP group play a key role in the regulation of the body weight and lipid metabolism in mammals.was to define the role of. The study group consisted of 38 subjects, including 27 men and 11 women qualified for endovascular aneurysm repair (EVAR). The subjects with abdominal aortic aneurysm were enrolled in the study group, depending on the body mass index (BMI); in obese patients (BMI > 30). The control group (n = 16) included subjects without lipid disorders. One-step isolation of RNA from lymphocytes and adipose tissue cells was performed using the modified TRI method by Chomc-zynski and Sacchi, and then the gene expression was tested by real-time PCR.. The highest mean relative of the gene expression for. Due to the important role of the

P-117 Pre-selected for an award: Bioinformatic analysis of NRF2 in the study of association of NRF2 variant and male infertility related to smoking status

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
D Aydos ◽  
O S Aydos ◽  
Y Yukselten ◽  
A Sunguroglu ◽  
K Aydos
Keyword(s):  
Dna Damage ◽  
Male Infertility ◽  
Mirna Expression ◽  
Smoking Status ◽  
Differentially Expressed ◽  
Control Group ◽  
Functional Variants ◽  
Significant Difference ◽  
Differentially Expressed Mirnas

Abstract Study question Could Nrf2 polymorphism (-617C>A; rs6721961) and oxidative stress (OS)-induced changes of signature seminal plasma (SP) miRNAs related to Nrf2 provide possible biomarkers of male infertility? Summary answer -617C>A SNP is associated with infertility through sperm OS DNA damage and miR-582-5p and miR-20a-5p, differentially represented between spermatozoa of smokers-non-smokers, might regulate Nrf2/ARE axis. What is known already As an extrinsic factor causing OS, smoking decreases male infertility by causing sperm membrane damage and DNA fragmentation. Expression of proteins related to the antioxidant defense system and phase 2 detoxifying enzymes controlled mainly by Nrf2/ARE pathway components is vital in managing OS-induced DNA damage. miRNAs, which multiple of are produced abundantly in male germ cells throughout spermatogenesis, have been detected in SP and contribute to multiple biological processes related to male reproductive events. miRNA-expression alterations may be induced in response to OS and without involving DNA sequence changes, miRNAs can provide additional mechanism of regulating the Nrf2 gene expression. Study design, size, duration Wild-type (WT) and SNP (-617) alleles in the Nrf2 gene were studied in 100 infertile cases and 100 controls and their associations with seminal parameters in relation to smoking status were assessed. In infertile cases, sperm DNA damage level was determined and compared among Nrf2 genotypes. Interactions between differentially expressed miRNAs (DEMIs) in response to smoking and Nrf2/ARE pathway components were visualized on a miRNA-mRNA regulatory network using CluePedia (v1.5.7) plugin of Cytoscape software (v3.8.2). Participants/materials, setting, methods Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was utilized to genotype the Nrf2 SNP (-617). DNA damages were analyzed by Comet assay. DEMIs were identified by a comprehensive bioinformatics analysis using the miRNA expression dataset GSE44134 downloaded from the GEO database. Predicted targets of DEMIs in smokers were identified by mirDIP portal. Known interactions between Nrf2 and its first neighbors were visualized after selecting STRING-actions, miRTarBase and miRecords validated miRNA source files from CluePedia panel. Main results and the role of chance There was significant difference for Nrf2 polymorphism between fertile and infertile males. The A allele was detected more frequently in the patient group; (P = 0.001). The frequencies of the C and A alleles of the Nrf2 were 62% and 38% in patients, and 78% and 44% in control group. The AA genotype was higher in the infertiles; 14% vs. 3% (P = 0.001). In smokers, sperm quality decreased significantly in AA genotype. The risk of DNA damage was highest with 224.58 AU in the AA genotype group, whereas it is the lowest with 164.56 AU in those carrying the CC genotype (P < 0.005). 21 differentially expressed miRNAs (including 7 downregulated and 14 upregulated in smokers) were identified. Among the upregulated DEMIs, miR-582-5p, miR-20a-5p, miR-573, miR-186-5p, miR-499a-5p were found to target the Nrf2 mRNA, suggesting their usage as biomarkers capable of indicating the antioxidant ability of the male reproductive system. The interrelations between Nrf2/Nrf2 direct interactors and DEMIs revealed the regulatory role of hsa-miR-20a-5p in SQSTM1/p62-Keap1-Nrf2 axis linked to selective autophagy. hsa-miR-582-5p was found to regulate the JNK/Jun/caspase-3 pathway, previously shown to be activated in response to OS, in which JUN can activate or suppress the Nrf2 expression. Limitations, reasons for caution Small number of cases while evaluating the effect of smoking weakens our ability to generalize the results. Including other coexisting factors and larger patient groups carrying other functional variants of Nrf2 as well as confirming the results at the protein level would further strengthen the results of the study. Wider implications of the findings This study is the first to report -617C>A polymorphism in the Nrf2 gene in the Turkish population and such a SNP may cause impaired fertility in men, especially in smokers, through oxidative metabolism. Considering these data may be valuable in determining risk groups. Trial registration number N/A

scholarly journals FSH for the Treatment of Male Infertility

2020 ◽  
Vol 21 (7) ◽  
pp. 2270 ◽  
Author(s):  
Livio Casarini ◽  
Pascale Crépieux ◽  
Eric Reiter ◽  
Clara Lazzaretti ◽  
Elia Paradiso ◽  
...  
Keyword(s):  
Male Infertility ◽  
State Of The Art ◽  
Hypogonadotropic Hypogonadism ◽  
Male Reproduction ◽  
Clinical Approach ◽  
Idiopathic Infertility ◽  
Infertile Men ◽  
First Case ◽  
New Compounds

Follicle-stimulating hormone (FSH) supports spermatogenesis acting via its receptor (FSHR), which activates trophic effects in gonadal Sertoli cells. These pathways are targeted by hormonal drugs used for clinical treatment of infertile men, mainly belonging to sub-groups defined as hypogonadotropic hypogonadism or idiopathic infertility. While, in the first case, fertility may be efficiently restored by specific treatments, such as pulsatile gonadotropin releasing hormone (GnRH) or choriogonadotropin (hCG) alone or in combination with FSH, less is known about the efficacy of FSH in supporting the treatment of male idiopathic infertility. This review focuses on the role of FSH in the clinical approach to male reproduction, addressing the state-of-the-art from the little data available and discussing the pharmacological evidence. New compounds, such as allosteric ligands, dually active, chimeric gonadotropins and immunoglobulins, may represent interesting avenues for future personalized, pharmacological approaches to male infertility.

scholarly journals P0690CORRELATIONS BETWEEN OPG/RANKL/RANK AXIS, VITAMIN D STATUS, PTH AND VASCULAR CALCIFICATION IN AN ADENINE-INDUCED MODEL OF CHRONIC KIDNEY DISEASE

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Beata Sieklucka ◽  
Tomasz Domaniewski ◽  
Marta Zieminska ◽  
Malgorzata Galazyn-Sidorczuk ◽  
Anna Pawlak ◽  
...  
Keyword(s):  
Gene Expression ◽  
Chronic Kidney Disease ◽  
Uric Acid ◽  
Kidney Disease ◽  
Vascular Calcification ◽  
Control Group ◽  
Urea Nitrogen ◽  
And Control ◽  
Rank Gene

Abstract Background and Aims Chronic kidney disease (CKD) is a major public health problem worldwide and refers to a wide range of disorders in bone and mineral metabolism, abnormalities of biochemical parameters and pathological calcification of the blood vessels. Vascular calcification (VC) is a common complication in CKD patients, contributes to cardiovascular disease (CVD), and associates with increased mortality and morbidity. The precise mechanism of VC in CKD is not yet fully understood. Recently discovered molecules such as osteoprotegerin (OPG), its ligand receptor activator of nuclear factor NF-κB ligand (RANKL) and RANK are not only well-known to play a crucial role in bone homeostasis, but they has also been implicated in the process of development of vascular complications However the exact role of OPG/RANKL/RANK axis in the process of VC has not been yet fully assessed. Thus, the aim of this work is to evaluate the role of OPG/RANKL/RANK axis in the process of calcification in CKD. Method Seventy two male Wistar rats weighing 260-290 g (8-weeks old) were initially divided into 6 groups containing 12 animals in each group. Rats were divided into six groups: control rats (K4, K6, K8) and CKD rats (B4, B6, B8). Control group rats received standard diet, whereas CKD rats were fed a low adenine – diet containing 0.3 % adenine, 1.0 % Ca, 1.2 % Pi through 4 (K4, B4), 6 (K6, B6) and 8 (K8, B8) weeks. Subsequently, CKD and control rats were sacrificed at weeks 4 (n=24), 6 (n=24) and 8 (n=24). One day before being killed, the rats were placed in metabolic cages for 24-hour urine collection. Thereafter, the rats were anesthetized and samples of blood, as well as aortas were collected. Next, the OPG, RANKL, parathyroid hormone (PTH), 25-hydroxyvitamin D (25(OH)D) and 1,25-dihydroxy vitamin D3 1,25(OH)2D3 concentrations were determined using appropriate ELISA kits. Then the sRANKL/OPG ratio was calculated. The OPG, RANK and RANKL gene expression was assessed using real-time PCR (RT-PCR). The VC was quantified by measurement of the arterial calcium (Ca) and phosphate (Pi) content using flame atomic absorption. Serum levels of urea nitrogen, creatinine, uric acid, Ca, Pi and urinary levels of creatinine, Ca and Pi were measured. Results There was a progressive increase in serum urea nitrogen, creatinine, uric acid and PTH of CKD rats in comparison to control values. We also observed significantly decreased levels of 25(OH)D, 1,25(OH)2D and serum Ca. Total Ca content in the aorta was significantly increased in CKD rats in comparison with control group, whereas total Pi content in the aorta was significantly increased only in B8 group in comparison to appropriate controls. There were no differences in serum OPG and sRANKL levels between CKD and control rats. In contrast, we observed decreased OPG, RANKL and RANK gene expression in a B4 group in comparison to appropriate controls, whereas in a B6 group we noticed increased OPG, RANKL and decreased RANK gene expression. B8 group revealed increased RANKL and RANK gene expression, but there were no differences in OPG gene expression between CKD rats and control group. Furthermore, we observed positive correlations between serum sRANKL and OPG and RANK gene expression. Ca and P content in the aorta inversely corelated with RANKL gene expression, whereas positively with OPG gene expression. Serum 25(OH)D concentrations correlated inversely with Ca in aorta. PTH was positively correlated with serum RANKL and OPG and gene expression these cytokines. Conclusion Our results suggest that OPG/RANK/RANKL axis may be involved in the process of vascular calcification in chronic kidney disease. However, its role and evaluation of precise mechanism in this field requires further evaluation.

scholarly journals miR-185 and SEPT5 Genes May Contribute to Parkinson’s Disease Pathophysiology

2019 ◽  
Vol 2019 ◽  
pp. 1-8 ◽  
Author(s):  
Arman Rahimmi ◽  
Ilaria Peluso ◽  
Aref Rajabi ◽  
Kambiz Hassanzadeh
Keyword(s):  
Gene Expression ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Substantia Nigra ◽  
Chromosomal Location ◽  
Gene Expression Pattern ◽  
Control Group ◽  
Significant Difference

There are still unknown mechanisms involved in the development of Parkinson’s disease (PD), which elucidating them can assist in developing efficient therapies. Recently, studies showed that genes located on the human chromosomal location 22q11.2 might be involved in the development of PD. Therefore, the present study was designed to evaluate the role of two genes located on the chromosomal location (miR-185 and SEPT5), which were the most probable candidates based on our bibliography. In vivo and in vitro models of PD were developed using male Wistar rats and SHSY-5Y cell line, respectively. The expression levels of miR-185, SEPT5, LRRK2, and PARK2 genes were measured at a mRNA level in dopaminergic areas of rats’ brains and SHSY-5Y cells using the SYBR Green Real-Time PCR Method. Additionally, the effect of inhibition on the genes or their products on cell viability and gene expression pattern in SHSY-5Y cells was investigated. The level of miR-185 gene expression was significantly decreased in the substantia nigra (SN) and striatum (ST) of the rotenone-treated group (control group) compared to the healthy normal group (P<0.05). In addition, there was a significant difference in the expression of SEPT5 gene (P<0.05) in the substantia nigra between two studied groups. The results of an in vitro study showed no significant change in the expression of the genes; however, the inhibition on miR-185 gene expression led to the increase in LRRK2 gene expression in SHSY-5Y cells. The inhibition on LRRK2 protein also decreased the cellular toxicity effect of rotenone on SHSY-5Y cells. The results suggested the protective role of miR-185 gene in preventing the development of PD.

scholarly journals Lung development, repair and cancer: A study on the role of MMP20 gene in adenocarcinoma

PLoS ONE ◽  
2021 ◽  
Vol 16 (4) ◽  
pp. e0250552
Author(s):  
Pooi Ling Mok ◽  
Arun Neela Kumar Anandasayanam ◽  
Hernandez Maradiaga Oscar David ◽  
Jiabei Tong ◽  
Aisha Farhana ◽  
...  
Keyword(s):  
Gene Expression ◽  
Wound Healing ◽  
Lung Adenocarcinoma ◽  
Lung Development ◽  
A549 Cells ◽  
Control Group ◽  
Wound Healing Assay ◽  
Transfected Cells ◽  
Tissue Organization

Multiple matrix metalloproteinases have significant roles in tissue organization during lung development, and repair. Imbalance of proteinases may lead to chronic inflammation, changes in tissue structure, and are also highly associated to cancer development. The role of MMP20 is not well studied in lung organogenesis, however, it was previously shown to be present at high level in lung adenocarcinoma. The current study aimed to identify the functional properties of MMP20 on cell proliferation and motility in a lung adenocarcinoma in vitro cell model, and relate the interaction of MMP20 with other molecular signalling pathways in the lung cells after gaining tumoral properties. In this study, two different single guide RNA (sgRNAs) that specifically targeted on MMP20 sites were transfected into human lung adenocarcinoma A549 cells by using CRISPR-Cas method. Following that, the changes of PI3-K, survivin, and MAP-K mRNA gene expression were determined by Real-Time Polymerase Chain Reaction (RT-PCR). The occurrence of cell death was also examined by Acridine Orange/Propidium Iodide double staining. Meanwhile, the motility of the transfected cells was evaluated by wound healing assay. All the data were compared with non-transfected cells as a control group. Our results demonstrated that the transfection of the individual sgRNAs significantly disrupted the proliferation of the A549 cell line through suppression in the gene expression of PI3-K, survivin, and MAP-K. When compared to non-transfected cells, both experimental cell groups showed reduction in the migration rate, as reflected by the wider gaps in the wound healing assay. The current study provided preliminary evidence that MMP20 could have regulatory role on stemness and proliferative genes in the lung tissues and affect the cell motility. It also supports the notion that targeting MMP20 could be a potential treatment mode for halting cancer progression.

150 Effect of bovine seminal plasma and sperm on endometrial gene expression

2019 ◽  
Vol 31 (1) ◽  
pp. 200
Author(s):  
B. Fernandez-Fuertes ◽  
J. M. Sanchez ◽  
S. Bages ◽  
P. Lonergan
Keyword(s):  
Gene Expression ◽  
Seminal Plasma ◽  
Reproductive Tract ◽  
Epididymal Sperm ◽  
Rna Integrity ◽  
Rna Quality ◽  
Rna Integrity Number ◽  
Maternal Immune System ◽  
Negative Effect

In cattle, most pregnancy losses are sustained before implantation. Many factors are involved in implantation failure, but in mice, pigs and humans there is increased evidence of a role for the maternal immune system and its regulation by seminal plasma (SP). However, there is little evidence for a role of SP in bovine fertility, where dilution or removal of SP before AI is routine. Therefore, the aim of this work was to determine the effect of bull SP or sperm on endometrial gene expression. To this end, 6 heifers were oestrous synchronised and slaughtered 12h after the onset of oestrus. Five endometrial explants from the horn ipsilateral to the preovulatory follicle were obtained from each animal. Explants were incubated with (1) RPMI medium (control); (2) epididymal sperm (106 epididymal sperm mL−1); (3) complete ejaculate (106 ejaculated sperm mL−1+25% SP); (4) ejaculated sperm alone (106 ejaculated sperm mL−1); and (5) SP alone (25% SP). Epididymal sperm were collected and pooled from the cauda epididymis of 3 bulls slaughtered in a commercial abattoir. In addition, complete ejaculates were obtained from 3 other bulls using an artificial vagina. After pooling the samples, a small volume was washed through a density gradient to obtain the ejaculated sperm, and the rest of the ejaculate was filtered to obtain sperm-free SP. The RPMI media was used to dilute sperm and SP to the working concentrations. After 6h of incubation, explants were snap frozen. The RNA quality was assessed with an Agilent 2100 bioanalyzer (Agilent, Santa Clara, CA, USA) before RT-qPCR analysis. Interestingly, SP had a dramatic effect on endometrium RNA integrity, as evidenced by a lower RNA integrity number in explants exposed to a complete ejaculate (2.4±0.14) or SP (2.4±0.06), in comparison with the control, epididymal sperm, or ejaculated sperm treatments (6.7±0.43, 6.9±0.32, 6.7±0.30, respectively; P&lt;0.05). Due to the low RNA quality, those treatments were excluded from further analysis. However, this finding is currently being explored, along with the possibility of this effect being inherent to species that ejaculate intravaginally. We then compared the ability of ejaculated sperm (which have been exposed to SP) and epididymal sperm (which have never had contact with SP) to regulate the endometrial expression of IL1A, IL1B, IL8, IL6, PTGES2, TNFA, and LIF. Although IL6, IL1A and LIF increased in all animals when exposed to either ejaculated or epididymal sperm, there was no effect of treatment. In conclusion, these data did not support the notion that exposure of sperm to SP is important for the immune regulation of the bovine uterus. In addition, the negative effect of SP on the endometrium, together with the fact that bulls are intravaginal ejaculators, suggests that any putative immunoregulatory role of this fluid in the cattle uterus is indirect. Further analysis of the effect of SP on the vagina and cervix will help elucidate whether this response is present in this species and whether it can propagate to more distal regions of the reproductive tract. This work was supported by Science Foundation Ireland (13/IA/1983, 16/IA/4474).

Parkinsonism-like disease induced by rotenone in rats: Treatment role of curcumin, dopamine agonist and adenosine A2A receptor antagonist

2021 ◽  
Vol 14 ◽  
Author(s):  
Asmaa Fathy Aboul Naser ◽  
Wessam Magdi Aziz ◽  
Yomna Rashad Ahmed ◽  
Wagdy Khalil Bassaly Khalil ◽  
Manal Abdel Aziz Hamed
Keyword(s):  
Oxidative Stress ◽  
Gene Expression ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Inflammatory Mediator ◽  
Adenosine A2a Receptor ◽  
Control Group ◽  
A2a Receptor ◽  
Adenosine A2a

Background: Parkinsonism is a neurodegenerative disorder that affects elderly people worldwide. Methods: Curcumin, adenosine A2AR antagonist (ZM241385) and Sinemet® (L-dopa) were evaluated against Parkinson’s disease (PD) induced by rotenone in rats and comparativelyrelatively compared with our previous study on mice model. Results: Rats injected with rotenone showed severe alterations in adenosine A2A receptor gene expression, oxidative stress markers, inflammatory mediator, energetic indices, apoptotic marker and DNA fragmentation levels as compare with the control group. Treatments with curcumin, ZM241385, and Sinemet® restored all the selected parameters. The brain histopathological features of cerebellum regions confirmed our results. By comparing our results with the previous results on mice, we noticed that mice respond to rotenone toxicity and treatments more than rats regarding to behavioral observation, A2AR gene expression, neurotransmitter levels, inflammatory mediator and apoptotic markers, while rats showed higher response to treatments regarding to oxidative stress and energetic indices. Conclusion: Curcumin succeeded to attenuate the severe effects of Parkinson’s disease in rat model and can be consider as a potential dietary supplement. Adenosine A2AR antagonist has almost the same pattern of improvement as Sinemet® and may be considered as a promising therapy against PD. By comparing the role of animal species in response to PD symptoms and treatments, our previous report on mice explore the response of mice to rotenone toxicity than rats, while rats showed higher response to treatments. Therefore, no animal model can perfectly recapitulate all the pathologies of PD.

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