Elevated expression of TSLP and IL-33 in Behçet's disease skin lesions: IL-37 alleviate inflammatory effect of TSLP.

The release of TSLP and IL-33 affect the skin integrity, which unsettled transcription factor regulators. We investigate TSLP and IL-33 in Behçet disease (BD) and we prove the effect of the anti-inflammatory cytokine IL-37 in BD skin lesions on TSLP production. TSLP, IL-33 and GATA-3/T-bet, were measured using PCR in BD skin lesions. We tested the suppressive effect of IL-37 on skin samples stimulated with a cytokine mixture inducing TSLP expression. TSLP and IL-33 were increased in BD patients particularly in patients having skin manifestations and correlate with indexed skin lesions. TSLP expression in BD with skin lesions correlates significantly with the transcription factors GATA3/Tbet ratio. The anti-inflammatory mediator IL-37 acted as a suppressor of TSLP-skin synthesis. The microenvironment in cutaneous lesions of BD patients' skin lesions is dominated by the expression of IL-33 and TSLP along an inflammatory Th2-type current. IL-37 acts as a booster to restore homeostasis.

Interleukin-37 in endometriosis.

Interleukin-37 (IL-37) has been identified as a novel anti-inflammatory cytokine. The present study aimed to evaluate the expression of IL-37 in serum and in peritoneal fluid to determine its clinical significance in endometriosis. Enzyme-linked immunosorbent assay (ELISA) was performed to examine serum IL-37 levels in patients with endometriosis and healthy controls. Peritoneal fluid IL-37 mRNA and NFκB expression were quantified by real-time reverse transcription polymerase chain reaction assays. The association of IL-37 levels with clinical factors and prognosis of endometriosis was analysed. We found that IL-37 levels in PF and in serum were significantly higher in patients with endometriosis compared to women without endometriosis (P=0.0005). IL-37 levels were highly expressed in PF [132.38±34.62pg/mL; P<0.0001] than in serum [74.10±13.49pg/mL] in endometriosis patients. IL-37 mRNA expression contrasted with NFκB mRNA expression in PF from patients with endometriosis. A significant inverse correlation was observed between IL-37 mRNA and NFκB mRNA expression. IL-37 expression correlates with endometriosis severity. The affected NFκB mRNA expression in endometriosis contributed the to exhibited increase of IL-37. The increased levels of IL-37 may dampen NFκB activation in endometriosis patients.

Vascular endothelial growth factor (VEGFA) gene variation in polycystic ovary syndrome in a Tunisian women population.

BACKGROUND: Polycystic ovary syndrome (PCOS) is characterized by the growth of a number of small cysts on the ovaries which leads to sex hormonal imbalance. Women who are affected by this syndrome suffer from irregular menstrual cycles, decline in their fertility, excessive hair growth, obesity, acne and most importantly cardiac function problems. The vascular endothelial growth factor (VEGF) plays a pivotal role in tissue vascularization in general and in the pathogenesis of many diseases. The PCOS was found to be associated with high expression levels of VEGF. In women who undergo assisted reproductive procedures (ART), VEGF was found to be a key mediator of other factors to control ovary angiogenesis. Here, we set out to examine the association of VEGFA gene polymorphism with PCOS and its components in a population of Tunisia women to enhance our understanding of the genetic background leading angiogenesis and vascularization abnormalities in PCOS. METHODS: The association of VEGFA gene with PCOS and its components was examined in a cohort of 268 women from Tunisia involving 118 PCOS patients and 150 controls. VEGFA gene variations were assessed through the analysis of the following SNPs rs699947 (A/C), rs833061 (C/T), rs1570360 (G/A), rs833068 (G/A), rs3025020 (C/T), and rs3025039 (C/T). The linkage disequilibrium between SNPs was assessed using HAPLOVIEW software while combination of SNPs into haplotypes in the population and the reconstruction of the cladogram were carried-out by PHASE and ARLEQUIN programs, respectively. Genetic association and genotype-phenotype correlations were calculated by logistic regression and non-parametric tests (Kruskall-Wallis and Mann-Whitney tests), respectively, using StatView program. RESULTS: We observed 10 haplotypes in our studied cohort whereH1 (ACGG), H2 (ACAG), H7 (CTGG) and H8 (CTGA) were the most frequent. We observed the association of the genotype CT of the SNP rs30225039 with PCOS phenotype (P = 0.03; OR 95 % CI = 2.05 [1.07-3.90]) and a trend for correlation of the pair of haplotypes H2/H2 with prolactin levels in plasma (P = 0.077; 193.5 ± 94.3 vs 45.7 ± 7.2). These data are consistent with literature and highlight one more time the role of vascularization in the pathogeny of PCOS. CONCLUSIONS: LD pattern in VEGF locus showed a similar LD pattern between the Tunisian population and the CEU. More haplotypes in the Tunisian population than in CEU was observed (22 haplotypes vs 16 haplotypes) suggesting higher recombination rate in Tunisians. The study showed that there was any advantage of using haplotypes compared with SNPs taken alone.

The influence of gonadotropins on clinico-biological ICSI outcome: a retrospective comparative study rFsH vs HP-hmg.

Objective To investigate the difference in the outcome of ICSI-ET cycles among respondents patients, taking into account the molecule inducer of controlled ovarian stimulation: HP-hMG ou rFSH. Patients and Methods A comparative retrospective study over 62 months including a total of 1005 infertile couples, divided into two groups: HP-HMG (n=125) and rFSH (n=880). Results - The average numbers of retrieved oocytes and matures oocytes were significantly higher in rFSH group rFSH (7,94 ± 2,49, HP-HMG vs 9,05 ± 3,40, rFSH, p=0.0001and  3±2,68, HP-HMG vs 6,65±3,05 , rFSH, p=0,02 respectively). There was no statistically significant difference in the endometrial thickness and estradiol level on hCG injection day, the total amount of administrated gonadotropin and the duration of stimulation. In addition, we did not find a significant difference between the two groups regarding the fertilization, the maturation, the cleavage, top quality embryo, implantation, clinical pregnancy, multiple pregnancies, live birth and miscarriage rates. There was no case of severe ovarian hyperstimulation syndrome. Conclusion - Inspite of a higher number of retrieved and mature oocytes obtained with rFSH, the latter showed no superiority over HP-hMG which seem to be equally efficient and safe for ICSI treatment cycles.

Haplotyping strategy highlights the specificity of FTO gene association with polycystic ovary syndrome in Tunisian women population.

The FTO (fat mass and obesity associated) gene was associated with different metabolic disorders in populations from different origins but with great difference between African and non-African populations. North-African populations combine many genetic backgrounds, among which African, Berber and Caucasian components, which makes North-Africans a good model for studying the genetic association of FTO. In the present investigation we explored the association of FTO gene with polycystic ovary syndrome (PCOS) in a population from Tunisia (n=278). Single nucleotide polymorphisms (SNPs) used in this study were previously associated in non-African populations: rs8050136 (A/C), rs9939609 (A/T), rs9930506 (G/A), or in both African and non-African populations: rs8057044 (A/G). Genotyping was performed by allelic discrimination method on StepOne real-time PCR system or KASPar technology. Linkage disequilibrium (LD) pattern was assessed by HAPLOVIEW and reconstruction of haplotypes was performed by PHASE, while statistical analyses were performed using StatView and GoldenHelix programs. Among the 13 haplotypes in the population, three (h1, h7 and h13) were strongly associated with PCOS notably h13 (P<0.0001, OR95%CI=0.040 [0.005-0.294]) while SNPs display weaker association. Moreover the LD pattern in FTO in the Tunisian population (r(2) index) was intermediary between those of Caucasian and Africans. This highlights the need for studying the genetics of complex disorders in the North-African populations taking into-account the haplotype structure of candidate loci more than SNPs taken alone.

[A retrospective study of 339 ICSI cycles: assesment of the two first years of activity of the Assisted Reproductive Technology Center of Aziza Othmana Hospital]. / Etude retrospective de 339 cycles d'injection intra cytoplasmique de spermatozoïdes: bilan des deux premières années d'activité de l'unité d'assistance médicale à la procréation de l'hôpital Aziza Othmana.

BACKGROUND: Intracytoplasmic sperm injection (ICSI) is a micromanipulation-assisted fertilization, whereby one spermatozoon is injected into the oocyte cytoplasm. Initially, ICSI was the treatment of choice for male factor infertility. However, because of the high fertilization and pregnancy rates achieved with this technique, the scope of the procedure has been widened to include couples with other causes of infertility. AIM: The aim of this study was to study the progression of the activity of the assisted reproductive technology's center of Aziza Othmana's Hospital and the ICSI results during the first two years. METHODS: Our study included 269 infertile couples who underwent 339 ICSI cycles between 1st May 2001 and 30 April 2003. Cycles with no oocytes obtained at the follicular aspiration and women aged over 40 years were excluded from this study. RESULTS: The number of ICSI cycles progressed in our center: 150 ICSI cycles in the 1st year, 189 ICSI cycles in the 2nd year. The mean number of picked-up oocytes was 8,8 +/- 5,6. The fertilization rate was 62%. The mean number of transferred embryos was 3,1 +/- 1,5. The pregnancy rate per transfer was 32,4%. The miscarriage rate was 28,4%. The take home baby rate was 67,9%. CONCLUSION: The number of couples undergoing ICSI cycles in our center is increasing. The fertilization rates and pregnancy rates in our center are similar to those published in the literature.