The effects of DICER1 and DROSHA polymorphisms on susceptibility to recurrent spontaneous abortion.

BACKGROUND: Recurrent spontaneous abortion (RSA) is a serious problem in pregnancy. The exact etiology of RSA is unknown in more than 50% of all the patients. However, genetic variations are known as susceptibility factors for idiopathic RSA. Considering the role of miRNA biosynthesis machinery in the miRNA production and effect of miRNAs on various diseases, this study aimed to evaluate the effects of DICER1 rs3742330 and DROSHA rs6877842 polymorphisms on RSA risk. METHODS: In this case-control study, 150 RSA patients and 195 age-matched healthy female controls were recruited. Both polymorphisms were genotyped using PCR-RFLP method. RESULTS: The frequency of DICER1 rs3742330AG genotype was higher in the control group (P = .022). There was a statistically significant association between rs3742330 polymorphism and a reduced RSA risk in dominant and allelic models (P = .013 and P = .007, respectively). No statistically significant association was found between DROSHA rs6877842 variant and RSA risk. The combination of AG and GC genotypes and G-G alleles of DICER1 rs3742330 and DROSHA rs6877842 polymorphisms led to a decreased RSA risk. However, the synergic effect of rs3742330A and rs6877842G alleles (A-G) and AA-GG genotypes was associated with an increased RSA risk. CONCLUSION: the DICER1 rs3742330AG genotype and combination of AG and GC genotypes and G-G alleles of DICER1 rs3742330 and DROSHA rs6877842 polymorphisms were associated with a reduced RSA risk.

The effect of miR-146a rs2910164 and miR-149 rs2292832 polymorphisms on preeclampsia susceptibility.

Preeclampsia (PE) is a gestational disorder and genetic and epigenetic alterations can affect its pathogenesis. Some evidences showed that the altered expression of miRNAs in the placentas complicated by PE. The blood samples from 219 PE and 242 normotensive pregnant women and placental tissue samples from 111 PE and 119 normotensive women were collected. MiR-146a and miR-149 polymorphisms were genotyped in blood samples and placentas using PCR-RFLP method. The frequencies of maternal miR-146a rs2910164 GC and CC genotypes did not differ between PE and control groups. However, the miR-146a rs2910164 G/C polymorphism was associated with an increased risk of PE in dominant (OR 1.5, 95% CI 1-2.1; P = 0.04) and allelic (OR 1.4, 95% CI 1-1.9; P = 0.04) but not recessive models. Moreover, the maternal GC and CC genotypes were associated with a 1.9- and 3.4-fold increased risk of severe PE (OR 1.9, 95% CI 1.1-3.2; P = 0.02 and OR 3.4, 95% CI 1.3-9; P = 0.01, respectively) and miR-146a rs2910164 polymorphism could increase risk of severe PE in dominant and recessive models (OR 2.1, 95% CI 1.3-3.4; P = 0.004 and OR 2.6, 95% CI 1-6.7; P = 0.04). The placental miR-146a rs2910164 polymorphism was associated with PE susceptibility in dominant (OR 1.8, 95% CI 1.1-3; P = 0.03) and allelic models (OR 1.7, 95% CI 1.1-2.5; P = 0.02). The frequencies of maternal and placental miR-149 rs2292832 genotypes were not different between two groups and these genotypes were not associated with PE or severe PE risk. In conclusion, according to logistic regression analysis the maternal/placental miR-146a rs2910164 G/C polymorphism was associated with PE and/or severe PE risk.

The association of the placental CASPASE-3 gene polymorphisms and preeclampsia susceptibility and in-silico analysis.

Preeclampsia is a pathologic complication of pregnancy, associated with increased apoptosis in the cytotrophoblasts as the main cause of this disorder. Caspase-3 is a key apoptosis-related enzyme that both mitochondrial and death receptor apoptotic pathways can activate. In this study, we aimed to investigate the effect of placental CASP-3 rs4647602 and rs4647610 polymorphisms on PE susceptibility. The placentas of 106 PE women and 115 normotensive pregnant women were collected. Genomic DNA was extracted from the placenta. For genotyping of CASP-3 rs4647602 and rs4647610 polymorphisms, polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used. The frequencies of placental CASP-3rs4647602CA and rs4647610GA genotypes were higher in PE women; however, the differences were not statistically different (P = 0.36 and P = 0.13, respectively). In addition, the frequencies of CA-GA combined genotypes and A-A haplotype were higher in PE women compared to the control women; however, the differences were marginally non-significant (P = 0.051 and P = 0.08, respectively). In-silico analysis revealed new enhancer and silencer motifs for mutant alleles of CASP-3rs4647602 and rs4647610 polymorphisms. In conclusion, placental CASP-3rs4647602 and rs4647610 polymorphisms were not associated with PE. Further studies with higher sample size are necessary to confirm or refute these findings.

Evaluation of Gamma Irradiation Effect on the Oxidative Stress Factors in Septic Rats Treated With Iranian Plant Essential Oils

ABSTRACT Cuminum cyminum L. (CM), Zataria multiflora Boiss. (ZM) and Mentha piperita L. (MP) are traditional medicinal plants with various pharmacological properties. This study was designed to assess the role of gamma irradiation -a modern decontamination method- in hepatoprotective effects of their essential oil (E.Os) in septic rats induced by experimental cecal ligation and puncture (CLP) model. The rats were divided into 20 groups; sham-operated (SOP); CLP; CLP + CM, ZM and MP (E.Os) (100 & 200 mg/kg b.w) and CLP + gamma irradiated (10 and 25 kGy) E.Os (100 & 200 mg/kg b.w) as treatment groups. All E.Os were injected i.p immediately after sepsis induction. 24 hour after CLP, the rats were sacrificed and the liver tissue was examined considering lipid peroxiation (LP), glutathione (GSH) and myeloperoxidase (MPO) activity. The results indicated that CLP operation caused significant (P<0.05) increase in the LP and MPO levels concomitant with decreased GSH level. Administration of the E.Os (100 and 200 mg/kg b.w) extracted from non irradiated plants as well as the irradiated (10 and 25 kGy) plant E.Os could significantly (P<0.05) modulate the levels of LP, MPO and GSH. It can be concluded that all E.Os even after irradiation exposure could modulate the oxidative injury parameters related to liver damages in CLP rat model. In conclusion, the plant irradiation didn't have any adverse effects on the hepatoprotective activities of the extracted oils.

The placental vascular endothelial growth factor polymorphisms and preeclampsia/preeclampsia severity.

Preeclampsia (PE) is a serious pregnancy-specific condition, which originates from placenta and finishes after delivery. The present study has investigated the association between placental VEGF I/D (rs35569394), -1154G/A (rs1570360), and -634G/C(rs2010963) polymorphisms and maternal VEGF -2549 I/D (rs35569394) polymorphism with PE and PE severity. In this case-control study, the maternal blood of 217 women with PE and 210 normotensive pregnant women and the placenta of 84 PE women and 103 normotensive women were collected after delivery. Genotyping was done by PCR or PCR-RFLP methods. The maternal VEGF-2549I/D genotypes were not associated with PE or PE severity. The placental VEGF -2549 I/D genotypes were not associated with PE too; however; the placental VEGF-2549 DD genotype was statistically different between women with severe PE and mild PE or the controls. The placental VEGF -634GC and CC genotypes were significantly higher in PE women and associated with 2.6 and 2-fold higher risk of PE, respectively. The VEGF -634GC and CC genotypes were associated with PE severity. No association was found between placental VEGF -1154G/A polymorphism and PE or PE severity. The placental DGC haplotype of VEGF -2549 I/D, -1154G/A, and -634G/C polymorphisms was associated with 2.9-fold higher risk of PE. However, the placental IAG haplotype was associated with 0.3-fold lower risk of PE. In conclusion, the placental VEGF -2549 DD genotype was associated with severe PE and the placental -634GC and CC genotypes were associated with PE and severe PE. No association was found between VEGF -1154G/A polymorphism and PE or PE severity.

The MDM2 promoter T309G polymorphism was associated with preeclampsia susceptibility.

PURPOSE: Preeclampsia (PE) is a hypertensive disorder of pregnancy in which abnormal proliferation and apoptosis of placenta trophoblast has a pivotal role in its pathophysiology. The aim of the current study was to examine the association between Mouse Double Minute 2 (MDM2) T309G and 40 bp insertion/deletion (I/D) polymorphisms and PE risk. METHODS: A case-control study was conducted on 208 PE women and 164 healthy pregnant women matching age, sex, and ethnicity. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and PCR methods were used for genotyping. RESULTS: The MDM2 309GG genotype was associated with PE, and this genotype was found to be a risk factor for PE. There was no association between the MDM2 I/D polymorphism and PE. The haplotype-based association analysis revealed no association between MDM2 T309G and 40 bp I/D polymorphisms and PE. The frequency of TT-DD and GG-DD combined genotypes were significantly higher in PE women with marginal P values (P = 0.046). CONCLUSIONS: The MDM2 309GG genotype was associated with higher risk of PE. The TT-DD and GG-DD combined genotypes were higher in PE women.

The -2549 insertion/deletion polymorphism of VEGF gene associated with uterine leiomyoma susceptibility in women from Southeastern Iran.

OBJECTIVES: Vascular endothelial growth factor (VEGF) is an important angiogenic factor that regulates angiogenesis and mediates sex steroid-induced cell growth. The present study investigated the association of VEGF gene-2578C/A (rs699947) and -2549 insertion/deletion polymorphisms in the promoter region of VEGF-A gene and uterine leiomyoma susceptibility in Southeast of Iran. MATERIAL AND METHODS: One hundred and fifty five women with uterine leiomyoma and 157 age, BMI, and ethnicity matched healthy women were enrolled in this study. VEGF gene -2578C/A polymorphism genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method, and the -2549 insertion/dele-tion polymorphism was analyzed by PCR method. RESULTS: The frequency of alleles and genotypes of VEGF-2578C/A polymorphism was not different between women with uterine leiomyoma and the controls; however, a significant association was revealed between II genotype of -2549 insertion/deletion (I/D) polymorphism of VEGF gene and uterine leiomyoma. CONCLUSIONS: The findings showed that VEGF gene -2549 insertion/deletion polymorphism was associated with uterine leiomyoma.

Combination effect of cytochrome P450 1A1 gene polymorphisms on uterine leiomyoma: A case-control study.

Uterine leiomyoma (UL) is an estrogen-dependent neoplasm of the uterus, and estrogen metabolizing enzymes affect its progression. This study aimed to evaluate the association between two single-nucleotide polymorphisms of cytochrome P450 1A1 (CYP1A1) gene and UL risk. The study consisted of 105 patients with UL and 112 healthy women as controls. Ile462Val (A/G) and Asp449Asp (T/C) polymorphisms of CYP1A1 gene were analyzed by DNA sequencing and polymerase chain reaction-restriction fragment length polymorphism methods, respectively. The findings indicated no association between Ile462Val (A/G) and Asp449Asp (T/C) polymorphisms of CYP1A1 gene and UL (p < 0.05). However, the combination effect of TT/AG genotypes of the Asp449Asp (T/C) and Ile462Val (A/G) polymorphisms was associated with 4.3-fold higher risk of UL. In addition, haplotype analysis revealed that TG haplotype of the Asp449Asp (T/C) and Ile462Val (A/G) polymorphisms could increase the UL risk nearly 4.9-fold. Asp449Asp (T/C) and Ile462Val (A/G) polymorphisms of CYP1A1 gene were not associated with UL susceptibility; however, the combination of the TT/AG genotypes and TG haplotype could increase the UL risk.

Effect of decompression on complete spinal cord injury in rats.

To examine whether spinal cord decompression improves functional recovery and decreases lesion volumes in paraplegic (not paraparetic) rats and, if so, at what postoperative time it is most efficacious. The spinal cords of 63 female rats were compressed at T9 with Yasargil clips. Rats were assigned randomly to five different treatment groups of 3 s, 1 hr, 6 hr, 3 weeks, and 10 weeks. Locomotor behavior scoring was based on the Basso, Beattie, Bresnahan (BBB) Locomotor Rating Scale (Ohio State University, Columbus, OH) motor scores. Comparing five groups, the mean BBB was statistically higher in the 3-s group (P < 0.05). Comparison of progressive changes in BBB in each group revealed statistically meaningful improvement in the 3-s group, too. Spared surface area of spinal cord was 81.5 +/- 4.9% in 3-s group and 10.8 +/- 1.4% in the delayed groups of decompression (P = 0.039). Rats undergoing immediate decompression showed significantly better functional recovery and smaller lesion volumes.

Usefulness of the tail-flick reflex in the prognosis of functional recovery in paraplegic rats.

BACKGROUND: This study examines whether return of the TFR is predictive of locomotor recovery after complete SCI in rats. METHODS: We evaluated TFRs in 39 adult female rats. The spinal cords of rats were compressed at T9 with Yasargil clips. The TFR and BBB were performed on each rat after surgery, at 24 hours, on the fourth day, and weekly. RESULTS: On the first day, all of these 39 rats had a BBB score of 0. Of these, the TFR in response to tail pinch was present in 16 (41%) cases. Of the 16 rats, 12 (75%) showed a gradual increase in BBB scores during subsequent weeks. However, in the 23 animals in which the TFR was absent, none showed improvement in BBB score or return of hindlimb movements. CONCLUSIONS: We conclude that after complete SCI, return of the TFR correlates strongly with return of motor activity.