The possible regulatory role of miR-514 and miR-642b in cumulus cells on the oocyte maturation in patients with polycystic ovary syndrome.

Polycystic ovary syndrome is a common endocrine disorder in reproductive-age women. Accordingly, abnormal microenvironment may negatively influence oocyte developmental competence as a result of the altered expression profile of cumulus cells (CCs), mainly the key players of oocyte maturation, such as epidermal growth factor receptor (EGFR) and prostaglandin E receptor-2 (PTGER2). This study aimed to examine the expression levels of miR-514, miR-642b, and their candidate target genes (EGFR and PTGER2, respectively) in CCs of immature and mature oocytes in patients with PCOS. A total of 40 oocytes at germinal vesicle (GV) and 40 oocytes at metaphase II (MII) stages were retrieved from 30 PCOS women. Quantitative real-time PCR was performed to analyze the expression level of miR-514, miR-642b, EGFR, and PTGER2 in cumulus cells (CCS) of each oocyte. The expression level of miRNAs and their candidate target genes were compared between CCs of GV and MII oocytes. Our study suggests an inverse relationship exists between the expression levels of miR-514 and EGFR, and miR-642b and PTGER2. Furthermore, we observed that CCs of GV oocytes had higher levels of EGFR and PTGER2 mRNA and lower levels of miR-514 and miR-642b expression compared to those of MII oocytes. The present study demonstrated that miR-514 and miR-642b can regulate oocyte development by targeting EGFR and PTGER2, respectively. Therefore, examination of these miRNAs in CCs could be promising parameters to predict oocyte competence in PCOS patients.

Racial, Ethnic, and Gender Diversity in United States Ophthalmology Clinical Trials.

Purpose: To investigate the representation of various gender, racial, and ethnic groups in ophthalmology clinical trials conducted in the United States (US) between 1997 and 2022. Design: Retrospective cross-sectional study. Participants: We included all participants in completed phase II/III, III, and IV ophthalmology clinical trials reported on the ClincialTrials.gov database. Methods: The proportional enrollment of each racial/ethnic and gender group in the clinical trials was calculated and compared with the US population. We also investigated the impact of various clinical trial features on the rate of reporting demographic information and enrollment of minorities. Main Outcome Measures: Proportional enrollment of each gender and race/ethnicity group compared with the US Census. Results: Of the total clinical trials included in the study, less than half (43.6%) provided information on the racial or ethnic backgrounds of their participants. The majority of the enrollees in trials were female (median: 57.5%, interquartile range [IQR]: 47.2%-65.8%). Among the trials that reported race and/or ethnicity data, White populations were overrepresented (median: 76.6%, IQR: 69.0%-84.0%, P = 0.001), and minorities, including Asian, Hispanic, and "other" groups, were underrepresented compared with the 2010 US Census (P < 0.001). Enrollment of Black individuals was found to be comparable to the US population estimates (median: 12.4%, IQR: 6.2%-20.8%, P = 0.44). The trial phase, the number of study participants, the primary clinical condition, and the year the trial started all affected demographic reporting and minority enrollments. Conclusions: Our findings highlight the need for increased efforts to promote diversity and inclusivity in ophthalmology clinical trials. Ensuring equitable inclusion of different gender, racial, and ethnic groups in the trials is essential for minimizing disparities and producing unbiased scientific findings generalizable to the entire population. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Expression of miR-21 &IL-4 in endometriosis.

BACKGROUND: Endometriosis characterized with existence of endometrial-like tissue outside the uterus. Fibrosis of ectopic lesions is an important feature of endometriosis. IL-4 induces fibrosis via fibroblast proliferation, collagen production and myofibroblast differentiation. Increasing of miR-21 expression promotes fibroblast activation and fibrosis expansion. The aim of study was to evaluate the expression of miR-21 and its relationship with IL-4 gene expression in endometrial ectopic and eutopic tissues of endometriosis patients. METHODS AND RESULTS: Ectopic and eutopic tissue samples were taken from 20 women with endometriosis, and control samples were taken from the endometrium of 20 endometriosis-free women. The relative expression of IL-4 and miR-21 evaluated by Real Time PCR. IL-4 relative gene expression was significantly increased in ectopic tissue compared to eutopic (p = 0.025) and control tissue (p = 0.021). The relative expression of miR-21 gene in ectopic tissue was increased compared to eutopic (p = 0.850) and control tissue (p = 0.978) but these differences were not significant. Also, the correlation between IL-4 and miR-21 relative gene expression was not significant (p = 0.083). CONCLUSION: The increased expression of miR-21 in endometrium of women with endometriosis may upregulate the IL-4 gene expression and lead to fibrosis. Further studies may suggest miR-21 and IL-4 as candidates for diagnosis of endometriosis.

Therapeutic potential of testosterone on sperm parameters and chromatin status in fresh and thawed normo and asthenozoospermic samples.

BACKGROUND: Hormonal changes alter the physiological level of ROS and cause oxidative stress in the cell. As estimated, hormonal deficiencies, environmental and ideological factors make up about 25% of male infertility. Pathogenic reactive oxygen species (ROS) is a chief cause of unexplained infertility. Limited studies exist on the effects of testosterone on human sperm culture. Therefore, in the current study, the effect of different doses of testosterone on sperm parameters and chromatin quality was investigated. MATERIALS AND METHODS: Semen samples from 15 normospermic and 15 asthenospermic patients were prepared by swim up method, and then were divided into four groups by exposing to different concentrations of testosterone (1, 10, and 100nM) for 45min. Samples without any intervention were considered as control group. All samples were washed twice. Sperm parameters and chromatin protamination were assessed in each group and the remains were frozen. After two weeks, all tests were repeated for sperm thawed. Also, the MSOM technique was used to determine the sperm morphology of class 1. RESULTS: Although sperm parameters were not show any significant differences in normospermic and asthenospermic samples exposed to different concentrations of testosterone before and after freezing, chromatin protamination was significantly decreased in the normospermic samples exposed to 10nM of testosterone before freezing (p<0.006), as well as 1 and 10nM of testosterone after freezing compared to control samples (p=0.001 and p=0.0009, respectively). Similarly, chromatin protamination in the asthenospermic samples was significantly decreased at concentration of 1nM of testosterone before and after freezing (p=0.0014 and p=0.0004, respectively), and at concentration of 10nM of testosterone before and after freezing (p=0.0009, p=0.0007) compared to control samples. CONCLUSION: Using a low dose of testosterone in the sperm culture medium, has positive effects on chromatin quality.

Population attributable fraction estimates of cardiovascular diseases in different blood pressure levels in a large-scale cross-sectional study: a focus on prevention strategies and treatment coverage.

OBJECTIVE: Hypertension is one of the major modifiable risk factors in developing cardiovascular diseases (CVD). Hence, we aimed to ascertain age- and sex-specific population attributable fraction (PAF) for CVD in different blood pressure levels to implement efficient preventive strategies at the population level. METHODS: Participants' data were obtained from the Iranian stepwise approach for surveillance of noncommunicable disease risk factors (STEPs) survey to calculate PAF in four subsequent phases. In phase 0, PAF was measured, irrespective of the diagnosis status. In phase 1, the theoretical minimum range of 115 ≤SBP less than 130 mmHg was considered as the low-risk and measurements equal to or higher than 130 mmHg as the high-risk group. Across phase 2, patients were divided into normal and hypertensive groups based on the American College of Cardiology/American Heart Association guideline. In phase 3, patients were divided into two categories based on treatment coverage. RESULTS: A total number of 27 165 participants aged ≥25 years had valid blood pressure measurements and were enrolled. Phase 0: PAF generally had an upward trend with age advancing. Phase 1: participants with BP ≥130 mmHg comprised the largest PAF, extending from 0.31 (0.25-0.37) in older male individuals to 0.85 (0.79-0.91) in younger females. Phase 2: higher values were found in younger ages for hypertension. Phase 3 represented that attributable fractions among hypertensive patients who received treatment were much lower than drug-naïve hypertensive participants. CONCLUSION: Our study enlightens the necessity for implementing effective screening strategies for the younger generation and providing adequate access to antihypertensive medications for the low-risk population.

Target gene repression mediated by miR-144 and miR-224 in cumulus cells is related to the success of oocyte in vitro maturation and fertilisation in patients with polycystic ovary syndrome (PCOS).

CONTEXT: In vitro maturation (IVM) of oocytes is an alternative approach for patients with polycystic ovary syndrome (PCOS) predisposing to ovarian hyperstimulation syndrome (OHSS). Transcriptomic analysis of cumulus cells (CC) may help make IVM more efficient. The aim of this study was to examine the impact of miR-144 and miR-224 and their candidate target genes (COX-2 and PTX-3 , respectively) expression on oocyte development in PCOS patients. METHODS: Immature oocytes were retrieved from 20 PCOS patients. After IVM, samples were divided into two groups: matured (M) and immatured (I) oocytes. ICSI was performed and the embryo quality was evaluated. qPCR was used to analyse miR-144, miR-224, COX-2 and PTX-3 expression levels in CCs of each group. KEY RESULTS: We found that the expression levels of miR-144 and miR-224 were lower and the COX-2 and PTX-3 mRNA levels were higher in CCs of M group than in CCs of I group. The expression level of miR-144 and miR-224 in unfertilised oocytes were higher than fertilised oocytes. The contrary results were observed for COX-2 and PTX-3 . A reduction pattern in the expression level of miR-144 and miR-224 and increasing pattern in the level of COX-2 and PTX-3 expression were observed in high quality compared to low quality embryos. CONCLUSIONS: The selected miRNAs were related to oocyte maturation, fertilisation and embryo development. These results support their critical involvement in oocyte development. IMPLICATIONS: Our findings may help reveal the mechanisms of post-transcriptional regulation by miR-144 and miR-224 during IVM procedure.

FTO genotype was associated with breast cancer in HER2 negative patients.

BACKGROUND: The fat mass and obesity-associated (FTO) gene may influence the risk of breast cancer (BC). The single nucleotide polymorphisms (SNPs) of FTO gene may exert different impacts on different types of BC. In this study, we investigated the association between FTO SNP rs9939609 and the status of estrogen receptor (ER), progesterone receptor (PR), P53, and human epidermal growth factor receptor-2 (HER-2) in BC patients. METHODS: Our case-control study was included 540 Iranian participants aged 35 to 70 (180 women with BC as the case group and 360 healthy controls). After genotyping for risk allele rs9939609 of the FTO gene, a logistic regression was applied to elucidate the association between FTO SNP rs9939609 and BC risk based on the receptor status. RESULTS: The number of HER-2 negative patients was significantly higher in FTO rs9939609 risk allele carrier group (61.5% vs. 41.4%, P < 0.05). A significant association was found between BC and rs9939609 FTO gene polymorphism only in HER2 negative BC patients (OR = 1.79, CI95%: 1.2-3.56, P = 0.03). No association was identified between FTO rs9939609 polymorphism and the status of ER, PR, and P53. CONCLUSION: We indicated that FTO SNP rs9939609 can be a potential therapeutic target particularly in HER-2 negative BC cases. The importance of this risk allele in BC pathogenesis needs to be further highlighted.

Evaluation of the FAS and FASL Gene changes in women with premature ovarian failure: A case-control study.

Background: Premature ovarian failure (POF), is menopause occurring before the age of 40, affecting 1-3% of women worldwide. The risk of POF increases with altered immunological parameters such as FAS and FASL genes, which play a fundamental role in embryogenesis and cellular homeostasis. Objective: The study aimed to investigate the potential role of FAS and FASL genes in POF pathogenesis. Materials and Methods: In this case-control study, the polymorphisms of FAS-670A/G and FASLIVS2nt_124A/G apoptotic genes were analyzed in 51 Iranian women suffering from POF, and 61 healthy controls. Isolation of DNA was done using the salting-out method, and genotypic analysis was performed for all the subjects using the polymerase chain reaction-restriction fragment length polymorphism method. Results: Our results revealed that homozygous FAS-670A/A and G/G, and heterozygous FAS-670A/G are not significantly different between cases and controls (p = 0.99). Also, in different genotyping models of FASIVS2nt_124, polymorphisms were not related to POF risk (p = 0.23). Conclusion: There is no statistical association between these polymorphisms and POF risk in women referred to genetic counseling clinics.

Association between different types of dietary carbohydrate and breast cancer.

BACKGROUND: Among modifiable lifestyle factors, unhealthy dietary intake is associated with higher risks of breast cancer (BC). This paper aimed to investigate the association of different types of dietary carbohydrate with BC risk among women 20-75 years old. DESIGN: This case-control study was carried out on 180 women with BC and 360 healthy individuals as the control group. Basic information including anthropometric measurements, medical history, physical activity, alcohol consumption, reproductive histories, smoking, and education level were collected. The amount of intake of carbohydrate, simple sugar, sucrose, maltose, and fructose were assessed using food frequency questionnaire (FFQ). RESULTS: The amounts of intake of total carbohydrate [odds ratio (OR) = 1.76; 95% confidence interval (CI) (1.24-2.14); P = 0.01], simple sugar (OR = 1.95, 95% CI (1.42-3.39); P = 0.01), sucrose (OR = 1.97, 95% CI (1.18-3.12); P = 0.02), maltose (OR = 4.07, 95% CI (1.68-8.14); P = 0.03), and fructose (OR = 1.104, 95% CI (1.06-1.36); P = 0.01) were positively associated with BC after adjustments for age, body mass index (BMI), smoking, using alcohol, physical activity, and dietary intake of calorie, protein, and fat. No significant association was found between the intake of glucose, galactose, and lactose with BC. CONCLUSIONS: The results of this study identified that some types of dietary carbohydrates may play a role in the development of BC. Different monosaccharides and disaccharides may have different effects on the risk of breast cancer. Further longitudinal studies are warranted to identify the effects of carbohydrates on BC and to explore the underlying mechanisms.

COVID-19 in patients with diabetes: factors associated with worse outcomes.

Purpose: Diabetes is one of the major comorbidities associated with COVID-19. We aimed to determine the clinical and epidemiological factors associated with the mortality of COVID-19 in diabetic patients in Iran, and also the impact of prescribed antiviral and antibiotics on patients' status. Methods: In this study, we used the national registry of hospitalized patients with Severe Acute Respiratory Syndrome (SARS) Symptoms with diabetes from February 18, 2020, to December 22, 2020. Demographic, clinical features, treatments, concurrent comorbidities, and their associations with mortality and severity outcomes were assessed using logistic regression. Results: 78,554 diabetic in-patients with SARS symptoms were included from 31 provinces of whom 37,338 were PCR positive for COVID-19. Older age and male gender are associated with COVID-19 mortality in diabetic patients. CVD is the most frequent comorbidity (42%). CVD, kidney disease, liver disease, and COPD are associated comorbidities which increased the risk of mortality. The mortality rate is higher in diabetic patients comparing to patients with no comorbidities, particularly in younger age groups. The frequency of antiviral, and antibiotics in COVID-19 positive patients was 34%, and 31%, respectively. Antibiotic treatment has no association with mortality in COVID-19 patients. Conclusions: Diabetic patients indicate higher mortality comparing to patients without any underlying comorbidities. Restrict strategies on increasing effective health care utilization must be considered in diabetic patients, especially in those with parallel underlying comorbidities. Regarding the antibiotic resistance issue and the noticeable use of antibiotics in diabetic patients, it is recommended to prioritize an antibiotic guideline prescription in COVID-19 patients for better stewardship by countries.

Interactions of anthropometric indices, rs9939609 FTO gene polymorphism and breast cancer: A case-control study.

Contradictory results were reported on the effect of fat mass- and obesity-associated (FTO) gene and anthropometric measurements on breast cancer (BC). This study aimed to assess the interactions between rs9939609 polymorphism of FTO gene, anthropometric indices and BC risk in Iranian women. This case-control study was performed on 540 women including 180 women with BC and 360 healthy women in Tehran, Iran. Physical activity and dietary intakes were assessed by validated questionnaires. Data on sociodemographic and pathologic factors of the participants as well as their blood samples were collected. The rs9939609 FTO gene polymorphism was genotyped using the tetra-primer amplification refractory mutation system-polymerase chain reaction (T-ARMS-PCR). No significant association was found between BC and risk allele of FTO rs9939609 polymorphism after adjustments for the confounders. However, there was a significant association between rs9939609 polymorphism risk allele and BC risk in females with overweight, even after adjusting for age, family history of BC, abortion, BMI and the number of pregnancies (P < .05). The association was disappeared after further adjustments for lifestyle factors including smoking, alcohol consumption, calorie and macronutrients intake, and physical activity. The FTO gene polymorphism was associated with the risk of BC in overweight individuals. This association was influenced by environmental factors including diet, alcohol consumption and smoking. Future studies are required to confirm the association between the FTO gene and BC in overweight females and to identify the underlying mechanisms.

Comparison of chromosomal instability of human amniocytes in primary and long-term cultures in AmnioMAX II and DMEM media: A cross-sectional study.

BACKGROUND: The genomic stability of stem cells to be used in cell therapy and other clinical applications is absolutely critical. In this regard, the relationship between in vitro expansion and the chromosomal instability (CIN), especially in human amniotic fluid cells (hAFCs) has not yet been completely elucidated. OBJECTIVE: To investigate the CIN of hAFCs in primary and long-term cultures and two different culture mediums. MATERIALS AND METHODS: After completing prenatal genetic diagnoses (PND) using karyotype technique and chromosomal analysis, a total of 15 samples of hAFCs from 650 samples were randomly selected and cultured in two different mediums as AmnioMAX II and DMEM. Then, proliferative cells were fixed on the slide to be used in standard chromosome G-banding analysis. Also, the senescent cells were screened for aneuploidy considering 8 chromosomes by FISH technique using two probe sets including PID I (X-13-18-21) & PID II (Y-15-16-22). RESULTS: Karyotype and interphase fluorescence in situ hybridization (iFISH) results from 650 patients who were referred for prenatal genetic diagnosis showed that only 6 out of them had culture- derived CIN as polyploidy, including mosaic diploid-triploid and diploid-tetraploid. Moreover, the investigation of aneuploidies in senesced hAFCs demonstrated the rate of total chromosomal abnormalities as 4.3% and 9.9% in AmnioMAX- and DMEM-cultured hAFCs, respectively. CONCLUSION: hAFCs showed a low rate of CIN in two AmnioMAX II and DMEM mediums and also in the proliferative and senescent phases. Therefore, they could be considered as an attractive stem cell source with therapeutic potential in regenerative medicine.

A comparative analysis of immunomodulatory genes in two clonal subpopulations of CD90+ amniocytes isolated from human amniotic fluid.

OBJECT: Immunosuppressive and immunomodulatory activity of mesenchymal stem cells derived from different sources, such as placental membranes, umbilical cord, and amniotic fluid has been proved. The heterogeneous nature of human amniocytes have been confirmed due to different clonal subpopulations found in amniotic fluid. The aim of this study was to investigate a 17-gene panel of immunomodulatory markers in two clonal subpopulations of CD90+ amniocytes, divided based on morphology into epithelioid and fibroblastoid cells. METHOD: Semi-quantitative RT-PCR was used to study the expression of the chosen genes. Flow cytometry analysis confirmed the non-hematopoietic mesenchymal origin of isolated cells, based on lacking the hematopoietic marker of CD31, and the presence of mesenchymal marker of CD90 (both on more than 90% of cells). RESULTS: Our results showed that besides growth characteristics, the two cell groups were different in expressional profile, so that, fibroblastoid clones displayed higher level of immunosuppression genes as well as mesenchymal surface marker of CD90 compared to epithelioid ones. Our previous investigation on these clones showed that epithelioid cells have a more potential to express the pluripotency genes. It seems there is an inverse relationship between genes associated with immunosuppression and pluripotency. CONCLUSION: Although many reports have been published regarding the immunosuppressive properties of fetal stem cells, but few studies to date have explained whether the stemness state of human amniocytes may affect their immunosuppressive potential. Further study on amniocytes, which often has self-renewal ability and high immunomodulatory potential, can help to understand the details of this relationship.

Investigating the expression of pluripotency-related genes in human amniotic fluid cells: A semi-quantitative comparison between different subpopulations, from primary to cultured amniocytes.

Various classifications have been proposed for human amniotic subpopulations, including classification of spindle-shaped (SS) and round-shaped (RS) cells, as well as the more referred triple-category of epithelioid (E-type) cells, amniotic fluid-specific (AF-type) cells and fibroblastoid (F-type) cells. The present study aims to investigate these amniotic subpopulations regarding the expression of some stem cell markers, including OCT4, NANOG, SOX2, C-KIT (CD117), C-MYC, KLF4, and THY1 (CD90). Flow cytometry was performed to characterize the isolated clonal subpopulations for a hematopoietic and a mesenchymal marker using PE-CD31 and FITC-CD90, respectively. A semi-quantitative RT-PCR analysis was carried out on the isolates in the second half of their lifespan when the cells were at the stationary phase of the growth curve. Characterization of isolated cells demonstrated that all clones including both epithelioid and fibroblastoid cells, had mesenchymal, not hematopoietic, lineage. RT-PCR analysis also revealed a higher expression of the target genes in epithelioid cells. Furthermore, the expression pattern of the genes and their correlations were remarkably different between primary- and long term-cultured amniocytes. Taken together, our results showed that the primary-cultured cells express the stemness genes equally, whereas the long term-cultured amniocytes exhibited a highly variable manner in the expression pattern of the genes. Diverse derivation site of amniocytes and individual genetic background can potentially explain the observed variation in the expression level of the target genes. These can also explain why amniocytes differ in many respects observed in our study, including survival rate, plastic adhesion, and growth characteristics.

Preimplantation genetic testing in assisted reproduction technology.

A significant proportion of clinically recognized pregnancies end in miscarriage. About 50 % of early pregnancy losses are due to chromosome abnormalities. In assisted reproduction technology (ART), a high proportion of top-quality embryos with morphological values are aneuploid whenever they have been evaluated in terms of genetic integrity in human preimplantation embryos either from in vitro or in vivo matured oocytes. It is plausible to think of preimplantation genetic testing (PGT) as a means of increasing pregnancy rates and minimizing the risk of fetal aneuploidy. It is believed that PGT will assume a prominent role in the field of ART, especially in a successful pregnancy, so it is embraced recently as a popular diagnostic technique. The PGT includes three sub-categories of PGT for aneuploidies (PGT-A), PGT for single gene / monogenic disorders (PGT-M), and PGT for chromosome structural rearrangements (PGT-SR). PGT-A is used to detect aneuploidies and previously it was known as PGS. PGT-M, formerly known as PGD, is intended to reduce monogenic defects. Previously known as PGS translocation, PGT-SR is PGT to identify structural chromosomal rearrangements. Since many of the old and new definitions for PGT are still vague and confusing for some researchers in the field of reproductive genetics, the main purpose of this study is to introduce all PGT classifications as well as elaborate on different aspects of this technology to improve ART outcomes.

The effect of vitamin C on the gene expression profile of sperm protamines in the male partners of couples with recurrent pregnancy loss: A randomized clinical trial.

OBJECTIVE: Since sperm abnormalities are known to be a major reason for recurrent pregnancy loss (RPL), any defects in DNA structure and chromatin condensation can place embryos at risk in the early stage of development and implantation. As antioxidants such as vitamin C may play a protective role against the destruction of protamine genes in sperm chromatin, this study was conducted to evaluate the effects of vitamin C on chromatin and the expression of protamine genes in the male partners of couples with RPL. METHODS: Twenty male partners of couples with RPL were selected as the intervention group and received vitamin C supplementation (250 mg daily for 3 months). Healthy fertile men (n=20) were included as controls. Sperm chromatin, DNA integrity, and the expression levels of protamine genes were evaluated before and after treatment. RESULTS: Significant differences were found in sperm morphology, protamine deficiency, and apoptosis between the two groups and before and after vitamin C administration. A significant change was found in mRNA levels of PRM1, PRM2, and the PRM1/PRM2 ratio after treatment. CONCLUSION: Daily oral administration of vitamin C may improve human sperm parameters and DNA integrity by increasing protamine gene expression levels in the male partners of couples with RPL. The beneficial effects of vitamin C supplementation as an antioxidant for the male partners of couples with RPL could lead to improved pregnancy outcomes in these cases.

Mitochondrial Aconitase in Neurodegenerative Disorders: Role of a Metabolism- related Molecule in Neurodegeneration.

BACKGROUND: Mitochondrial aconitase (Aco2), a member of the family of iron-sulfur [4Fe- 4S]-containing dehydratases, is involved in cellular metabolism through the tricarboxylic acid cycle. Aco2 is highly susceptible to oxidative damage in a way that exposure to the reactive species and free radicals leads to release of iron from the central [4Fe-4S] cluster resulting in the production of the inactive form of Aco2. OBJECTIVE: There is increasing evidence supporting a direct association between impaired energy metabolism and the incidence and progression of neurodegenerative disorders in neuronal cells. RESULTS: It has been shown that alteration in bioenergetic parameters is a common pathological feature of the neurodegenerative diseases leading to neuronal dysfunction. Numerous studies have demonstrated that dysfunctional Aco2, among the other bioenergetic parameters, is a key factor that could promote neurodegeneration. CONCLUSION: Increasing our knowledge about energy metabolism-related molecules including Aco2 affected by neurodegenerative disorders might be useful to find an efficient therapeutic strategy for those central nervous system-related diseases. Accordingly, in this review, we have focused on the events and processes that occur in neurodegeneration, leading to the inactivation of Aco2 in the brain.

Tumor Necrosis Factor Alpha -308 G/A Single Nucleotide Polymorphism and Risk of Sperm Abnormalities in Iranian Males.

BACKGROUND: Signaling molecules such as cytokines regulate spermatogenesis during the maturation of germ cells and sperm apoptosis. Tumor necrosis factor alpha (TNFα) is one of the most-documented cytokines that is involved in spermatogenesis. We investigated the association of the TNFα -308 G/A single nucleotide polymorphism with sperm abnormalities in Iranian males. MATERIALS AND METHODS: This case-control study included 180 infertile men who re- ferred to Yazd Research and Clinical Center for Infertility and 100 healthy normospermic controls. Infertile men were classified into four groups of azoospermia (n=91), oligospermia (n=26), teratospermia (n=30) and asthenoteratospermia (n=33). After sperm analysis, DNA was extracted from blood and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was carried out for the genotyping of TNFα- 308 G/A. RESULTS: The A allele was significantly associated with sperm abnormality in our population [(P<0.001, odds ratios (OR) 95% confidence interval (CI)=2.31]. In addition, the A allele was also associated with azoospermia (P<0.001, OR (95% CI)=2.484), oligospermia (P=0.005, OR (95% CI)=2.51) and teratospemia (P<0.001, OR (95% CI)=3.385) but not with asthenoteratospermia (P=0.623). CONCLUSION: Our data suggest that this single nucleotide polymorphism (SNP) maybe associated with the risk of sperm abnormality in infertile men of Iranian origin.