NLF2 gene expression in the endometrium of patients with implantation failure after IVF treatment.

The aim of this study was to analyze the expression of microfibril-associated protein 2 (MFAP2), microfibril-associated protein 5 (MFAP5) and nuclear localized factor 2 (NLF2) genes in patients with repeated IVF failure and compare with fertile population. Total RNA was isolated from 38 patients (repeated implantation failure, group 1, n=22; fertile patients, group 2, n=16). mRNA expression levels were measured quantitatively using real-time polymerase chain reaction. Our results showed that mRNA expression of NLF2 significantly decreased in the infertility group as compared to control group (P=0.023). In addition a marked decrease was observed in the expression of MFAP2 in women with repeated implantation failure. In conclusion, NLF2 gene expression levels and differences in MFAP2 and MFAP5 gene expressions (albeit being insignificant) between infertile group and control group draw attention to a genetic basis under implantation failure.

Gingival crevicular fluid levels of osteoprotegerin (OPG) in premenopausal and postmenopausal women with or without chronic periodontitis.

OBJECTIVES: Systemic conditions may affect host susceptibility, disease progression and severity as well as treatment response. Previously, low oestrogen (E(2)) levels were associated with increased bone resorption, due to increased osteoclastogenesis and decreased osteoclast apoptosis. Osteoprotegerin (OPG) is an essential cytokine for osteoclastogenesis. The aim of this study was to evaluate gingival crevicular fluid (GCF) OPG levels in menopausal and premenopausal patients with or without periodontitis, and effects of phase I periodontal therapy on GCF OPG levels. METHODS: Forty-four systemically healthy premenopausal and menopausal patients were recruited and divided into subgroups of periodontitis and control. Bone mineral density (BMD) and serum E(2) levels were measured. Before and after phase I periodontal therapy clinical indices, including clinical attachment levels (CAL) were recorded, and GCF samples were collected. GCF OPG levels were detected by enzyme-linked immunosorbent assay. Repeated measurement ANOVA and Spearman correlation tests were used. RESULTS: All clinical indices improved significantly after treatment(p<0.001), except Pre-M/C groups CAL reduction(p>0.05). Periodontitis groups' OPG levels were lower than gingivitis groups(p>0.05). Following periodontal phase I therapy, GCF OPG levels increased markedly in all groups, however this alteration was found statistically insignificant (p>0.05). CONCLUSIONS: The current data revealed that GCF OPG levels were lower in periodontitis patients and phase I therapy resulted with increased GCF OPG levels, however those alterations were statistically insignificant. In addition, present data suggested that menopause do not seem to have a significant effect on periodontal status or response to phase I treatment, within the limits of this study.

A prenatal tertiary trisomy resulting from balanced maternal 8; 9 translocation.

An additional derivative chromosome 8 was found in the cytogenetic analyses of the chorionic villus biopsy specimen of a balanced reciprocal translocation carrier mother. This was a 3:1 segregation of the unbalanced product of the balanced maternal 8:9 translocation. The chromosomes of the carrier of the balanced reciprocal translocation pair with their matching homologous segments at meiosis I, a quadrivalent figure is formed and chromosomes segregate from this configuration. Increased nuchal tranaslucency was also determined on fetal sonography at the 13(rd) week of gestation. The final karyotype was 47,X Y,+der(8)t(8;9)(q11.2;p22) mat, and the parents were informed about this tertiary trisomy. After genetic counseling, the parents decided to terminate the pregnancy. The presented case is a reminder of the probability of the unbalanced products of the 3:1 segregation, rather than the common 2:2 segregation.

Expression of the imprinted IGF2 and H19 genes in the endometrium of cases with unexplained infertility.

OBJECTIVE: As genomic imprinting plays a critical role in the development of the placenta, the aim of this study was to detect whether the expression levels of the imprinted genes IGF2 and H19 in the endometrium differ between infertile and fertile women. STUDY DESIGN: Total RNA was extracted from 30 (15 unexplained infertile and 15 fertile) women's endometrial tissue. cDNA was synthesized from total RNAs of each sample. IGF2 and H19 mRNA expression levels were measured quantitatively using the Real Time PCR method. In order to determine the allelic expression of IGF2 and H19, genomic DNA was extracted from endometrial tissues. RESULTS: When compared with the control group, increased mRNA expression of IGF2 was detected (1.5-fold change, P=0.015) in the unexplained infertility group. In contrast, H19 expression was lower in the infertility group as compared to the control group (4-fold change, P<0.0001). Restriction analysis of cDNA-derived PCR product showed that all patients and controls indicated monoallelic expression of IGF2 and H19. CONCLUSION: Our results showed that altered expression of these imprinted genes might affect implantation and that their timely and appropriate activation is important for proper functioning. To understand the molecular epigenetic basis of implantation and placental development, genomic imprinted genes should be further investigated.

Endometrial mRNA expression of matrix metalloproteinases, their tissue inhibitors and cell adhesion molecules in unexplained infertility and implantation failure patients.

The aim of this study was to analyse whether some cases of unexplained infertility and implantation failure after IVF could be explained by different expression levels of the matrix metalloproteinases (MMP-2, 9), their tissue inhibitors (TIMP-2, 3) and intercellular (ICAM-1) and vascular (VCAM-1) adhesion molecules in endothelial cells. Total RNA was extracted from the endometrial tissues of 41 women (unexplained infertile, group 1, n = 15; fertile volunteers, group 2, n = 15 and patients with implantation failure after IVF, group 3, n = 11). MMP-2, MMP-9, TIMP-2, TIMP-3, ICAM-1 and VCAM-1 mRNA expression levels were measured quantitatively using real-time polymerase chain reaction. In the endometrium from women with unexplained infertility and implantation failure after IVF, MMP-2 and TIMP-3 expression were significantly decreased when compared with the fertile group (P < 0.05 and P

Lack of association between -460 C/T and 936 C/T of the vascular endothelial growth factor and angiopoietin-2 exon 4 G/A polymorphisms and ovarian, cervical, and endometrial cancers.

Tumor growth, which employs a number of regulators, requires the formation of new blood vessels. The most important regulators are vascular endothelial growth factor (VEGF) and angiopoietin-2 (ANGPT-2). DNA sequence variations in VEGF and ANGPT-2 genes may lead to altered productions and/or activities of these genes. In this study, we aimed to determine the polymorphic effects of the changes in the VEGF -460 C/T, VEGF 936 C/T, and ANGPT-2 exon 4 G/A, which we perceive as risk factors in the progress and metastasis of cancer, on the gynecologic cancer patients in the Turkish population. Forty-seven ovarian, 32 cervical, and 21 endometrial cancer patients and 106 healthy controls were studied. The genomic DNA was extracted from the whole blood by using DNA extraction techniques. DNA samples were analyzed by polymerase chain reaction and restriction fragment length polymorphism. There were no significant differences between any of the three types of gynecologic cancer patients and controls in terms of the distribution of VEGF -460, VEGF 936, and ANGPT-2 genotypes and alleles (p > 0.05). Odds ratios (ORs) were calculated by logistic regression analysis in comparison with the most common homozygote genotype observed in the studied population. No evidence of a relationship that would constitute a risk factor (p > 0.05) was found between genotype and allele frequencies of patients and controls for VEGF -460, VEGF 936, and ANGPT-2 genes. A multivariable logistic regression analysis with the involvement of covariant factors, such as the history of gynecologic cancer and/or other cancer types in the family, stages of tumor, smoking habits, and existence of other diseases, did not change the results. The present study is the first case-control study of VEGF and ANGPT-2 polymorphisms in relation to ovarian, cervical, and endometrial cancers.

An investigation of relationships between hypoxia-inducible factor-1 alpha gene polymorphisms and ovarian, cervical and endometrial cancers.

BACKGROUND: DNA sequence variations in HIF-1 alpha gene might yield changes both in the production outcomes and in the activities of the gene. Overexpression of the HIF-1 alpha subunit, resulting from intratumoral hypoxia and genetic alterations, has been demonstrated in common human cancers and is correlated with tumor angiogenesis and patient mortality. In this study, we aimed to determine how the three single nucleotide polymorphisms (SNPs, C1772T and G1790A exon 12, C111A exon 2) in the HIF-1 alpha gene coding regions affect the ovarian, cervical and endometrial cancer patients in the Turkish population. A study on this relationship has not been conducted to date. METHOD: 102 gynecologic cancer patients and 107 healthy controls were studied. Genotypes of the three polymorphisms were analyzed by PCR-RFLP. RESULTS: There was no significant difference between ovarian cancer patients and controls in terms of the distribution of C1772T genotypes and alleles (P>0.05). However, there was a highly significant increase in the frequency of both CT 1772 and TT 1772 genotypes in patients with cervical and endometrial cancers compared with healthy controls. In fact, 1772T allele-carriers (CT+TT genotypes) showed an association with the risk of cervical and endometrial cancers compared to the wild type (OR=3.84, 95% CI: 1.65-8.93; OR=7.41, 95% CI: 2.33-23.59, respectively). C1772T polymorphism was not associated with family history concerning gynecologic and/or other cancer types, stages (I-IV) and grades of tumor, smoking habits and existence of other diseases that generate a hypoxic microenvironment even after multivariable logistic regression analysis. As for HIF-1 alpha G1790A genotypes, the frequencies of G alleles were 98% in ovarian patients and 100% in the control group. We found no significant difference in the genotype distribution and allele frequencies between the ovarian patients and healthy control subjects. There were no GA and AA genotypes among the cervical and endometrial cancer patients. As for HIF-1 alpha C111A polymorphism, we did not find CA and AA variants of the gene in controls or in any of the three types of patients. CONCLUSION: Our results suggest that the C1772T polymorphism of the HIF-1 alpha may be associated with cervical and endometrial cancers.