Network


Latest external collaboration on country level. Dive into details by clicking on the dots.

Hotspot


Dive into the research topics where Hatem Elghezal is active.

Publication


Featured researches published by Hatem Elghezal.


Urology | 2011

Semen Parameters and Sperm DNA Fragmentation as Causes of Recurrent Pregnancy Loss

Sonia Brahem; Meriem Mehdi; Hanène Landolsi; Soumaya Mougou; Hatem Elghezal; Ali Saad

OBJECTIVES To evaluate and compare standard sperm parameters, and sperm DNA fragmentation in seminal ejaculates from men whose partners had a history of recurrent pregnancy loss (RPL) and in a control group of men who had recently established their fertility. METHODS Semen samples from 31 patients with a history of recurrent pregnancy loss and 20 men with proven fertility were analyzed according to World Health Organization guidelines. Sperm DNA fragmentation was detected by the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay. RESULTS When sperm quality of the control group was compared with that of the RPL group, a significant difference was observed in sperm motility, but not in other parameters. The mean number of sperm cells with fragmented DNA was significantly increased in the RPL group (32.22 ± 6.14%) compared with control donors (10.20 ± 2.1%). CONCLUSIONS Our data indicate that sperm from men with a history of RPL have a higher incidence of DNA damage and poor motility than sperm from a control group, and this can explain in part the pregnancy loss in these patients.


Journal of Assisted Reproduction and Genetics | 2011

Detection of DNA fragmentation and meiotic segregation in human with isolated teratozoospermia

Sonia Brahem; Meriem Mehdi; Hatem Elghezal; Ali Saad

PurposeTo evaluate levels of DNA fragmentation and chromosomal abnormalities in ejaculated sperm of males with isolated teratozoospermia and to determine if specific sperm morphological types occur simultaneously with these nuclear defects.MethodsSperm obtained from isolated teratozoospermic men (n = 70) and fertile men (n = 30) were analysed using fluorescence in situ hybridization and TUNEL assay.ResultsTeratozoospermic men, compared to fertile men, showed significantly higher rates of sex chromosomes disomy, and diploidy. Significant correlations were found between amorphous head, microcephalic head, short tail, and sex chromosomes disomy. Level of sperm DNA fragmentation was significantly higher in teratozoospermic men than in controls and positively correlated to the incidence of macrocephalic heads, amorphous heads, and short flagella.ConclusionsPatients with isolated teratozoospermia have increased levels of DNA fragmentation and chromosomal aneuploidy. Some specific morphological abnormalities were shown to be predictive of chromosomal abnormalities and DNA alteration.


Urology | 2011

Analysis of Sperm Aneuploidies and DNA Fragmentation in Patients With Globozoospermia or With Abnormal Acrosomes

Sonia Brahem; Meriem Mehdi; Hatem Elghezal; Ali Saad

OBJECTIVES To evaluate the levels of DNA fragmentation and aneuploidy rate in ejaculated sperm of men with globozoospermia and men with a predominance of abnormal acrosomes. METHODS The semen samples obtained from 2 globozoospermic men, 8 patients with a predominance of abnormal acrosomes, and 20 fertile men were analyzed using the fluorescence in situ hybridization and the terminal desoxynucleotidyl transferase-mediated deoxyuridine triphosphate biotin nick-end labeling assay. Dual fluorescence in situ hybridization for chromosomes 8 and 12, and triple fluorescence in situ hybridization for chromosomes X, Y, and 18 were performed. RESULTS The patients with globozoospermia and those with a predominance of abnormal acrosomes had a significantly greater percentage of sperm with DNA fragmentation compared with the controls (P < .01). In addition, a modest increase in the frequency of sex chromosome aneuploidy and disomy 8 was found in these patients compared with the controls (P < .01). A significant correlation was established between the abnormal acrosome and chromosomal aneuploidy. CONCLUSIONS The high level of DNA fragmentation, in addition to moderate chromosomal abnormalities, might contribute to the low fertilization rate and poor pregnancy prognosis reported in the present category of patients.


Environmental Toxicology and Pharmacology | 2011

Assessment of chromosomal aberrations, micronuclei and proliferation rate index in peripheral lymphocytes from Tunisian nurses handling cytotoxic drugs

Sana Bouraoui; Aicha Brahem; Faten Tabka; Najib Mrizek; Ali Saad; Hatem Elghezal

Anti-neoplastic agents are widely used in the treatment of cancer and some non-neoplastic diseases. These drugs have been proved to be mutagens, carcinogens and teratogens. To check the eventual effects of anti-cancer drugs on occupationally exposed Tunisian nurses, we used chromosomal aberration assay and micronucleus assay. Both parameters have been used to evaluate cellular DNA damage in the biological monitoring of occupationally exposed workers and each assay has its own aim .We used the proliferation rate index to evaluate the cytotoxic effect of antineoplastic drugs in exposed nurses. The frequency of binucleated micronucleated cells was significantly higher in nurses handling cytostatic drugs than in control. We detected also a significant increase of structural chromosomal aberrations. Control subjects generally had significantly higher values of proliferation rate index compared to expose ones. Our results confirm the genotoxic and the cytotoxic effects of antineoplastic drugs in blood lymphocytes circulation. This study points to the necessity to work under more safe and controlled conditions during the preparation and the administration of anti-cancer drugs.


Hematological Oncology | 2008

Cytogenetic analysis of 298 newly diagnosed cases of acute lymphoblastic leukaemia in Tunisia.

Abir Gmidène; Hlima Sennana; Hatem Elghezal; Sihem Ziraoui; Yosra Ben Youssef; Moez Elloumi; Lamia Issaoui; Imed Harrabi; Sophie Raynaud; Ali Saad

Genetic changes associated with Acute Lymphoblastic Leukaemia (ALL) provide diagnostic and prognostic information with a direct impact on patient management. We report the cytogenetic analysis of 298 Tunisian patients with ALL, including 183 children and 115 adults. Chromosome abnormalities have been detected in 68.2% of our patients associating clonal numerical and/or structural rearrangements. Some chromosomal abnormalities especially hyperdiploidy, 19p13 abnormalities, 8q24 translocations, 12p, 6q deletions and TCR rearrangements occur at a lower incidence compared to that reported in other populations. ALL cases (5.7%) had miscellaneous clonal abnormalities. We also found in our Tunisian series a higher incidence for T‐lineage ALL more than usually described. Among structural chromosomal abnormalities, t(9;22)(q34;q11) resulting in the BCR/ABL fusion and the t(12;21)(p13;q22) resulting in the TEL/AML1 fusion were studied by FISH providing additional diagnostic and prognostic information. We conclude that although the incidence of our cytogenetic results are slightly different, their clinical significance is similar to that described in the literature. Copyright


Clinical Endocrinology | 2009

A novel BMP15 variant, potentially affecting the signal peptide, in a familial case of premature ovarian failure.

Besma Lakhal; Paul Laissue; Rim Braham; Hatem Elghezal; Ali Saâd; Marc Fellous; Reiner A. Veitia

Premature ovarian failure (POF) is a frequent pathology leading to infertility. Clinically, it is characterized by at least 6 months of amenorrhoea in women under 40 years of age and is associated with high plasma levels of gonadotrophins. The aetiology of POF includes immunological, infectious, iatrogenic and genetic factors. Chromosomal alterations, as well as mutations in autosomal and X-linked genes have been associated with POF. Unfortunately, approximately 80% of cases remain idiopathic. BMP15 is a growth factor encoded by an X-linked gene. It is expressed by oocytes from early follicular developmental stages onwards and regulates granulosa cell mitosis and proliferation (1,2 and references therein). BMP15 is synthesized as an inactive precursor (pre-propeptide), involving an N-terminal signal peptide, a propeptide and a C-terminal region containing the mature protein. To release the mature bioactive domain, extensive posttranslational processing, including signal peptide removal, dimerisation and further cleavage is required. The relevance of BMP15 in reproduction has been demonstrated in animal models. For instance, homozygous BMP15 mutations in sheep produce infertility. In mice, although heterozygous inactivation of Bmp15 leads to normal ovarian function, Bmp15 animals are hypofertile because of a reduced ovulation rate and fecundity (1–3 and references therein). The first human BMP15 mutation was described in two sisters affected with POF, who carried the heterozygous point mutation c.704A>G (p.Tyr235Cys). This substitution leads to an alteration in the proregion and induces a dominant negative effect on the normal protein, impairing granulosa cell proliferation. Since then, we and others have screened more than 600 POF women for BMP15 variants. Several alterations (i.e. p.Arg61Trp, p.Glu211X and p.Leu148Pro), which are absent in control populations and that are located in the proregion, have been reported. Here, we describe a novel BMP15 variant detected during screening of 30 probands of familial POF cases. The patient carrying the mutation is a 23-year-old woman of Tunisian origin presenting with secondary amenorrhoea and high plasma gonadotrophin levels (FSH: 110 UI/L and LH: 34 UI/L). She has no clinical history of autoimmunity, pelvic surgery or chemotherapy and has a normal 46,XX karyotype. Direct sequencing of the BMP15 coding region revealed the heterozygous substitution c.13A>C (p.Ser5Arg at the protein level). This variant was also found in her 46,XY sex-reversed sister (SRY-positive without ambiguities of the external genitalia). Although the link between sex reversal and the variant is unclear, its presence in a 46,XY individual shows that the mother also bears the mutation (maternal DNA was unavailable). The clinical history of the mother showed that she also had an early menopause (at 36 years of age). This is in agreement with this variant being linked to POF in this family. Moreover, this mutation has never been detected in control populations (from previous studies) and was absent in 108 X chromosomes, of which 28 came from the same geographic area (i.e. control women having at least one child and no personal history of infertility or autoimmune disease). BMP15 c.13A>C is also unknown in the SNP database of the NCBI (http:// www.ncbi.nlm.nih.gov/sites/SNP). The relevant Ser5 residue lies within the signal peptide of the protein. Figure 1 shows that Ser5 is conserved in mammalian BMP15 sequences. To assess objectively the potential deleterious effect of the amino acid change we used the sift (Sorting Intolerant From Tolerant) software (http://www.blocks. fhcrc.org/sift/SIFT.html) and the sequence alignment displayed in Fig. 1a. SIFT uses protein sequence conservation data to calculate the probability of an amino acid substitution of being deleterious. Scores lower than 0.05 suggest a potential pathogenicity. The score obtained for the p.Ser5Arg variant was very low (0.01). Indeed, the substitution Ser>Arg translates into an important change in polarity. Serine is a small polar non-ionisable amino acid whereas arginine is a strongly basic and positively charged at pH 7. Such a substitution might alter the hydrophobic character of the N-terminus of BMP15, thus interfering with the function and processing of the signal peptide. To assess whether this variant was indeed able to alter the signal peptide, we used two prediction programs. According to both phobius (http://www.phobius.cgb.ki.se/) and signalp (http://www.cbs.dtu.dk/services/SignalP/), the conserved sequence underlined in the alignment of Fig. 1a does contain a signal peptide and the variant p.Ser5Arg decreases the ‘signal-peptide character’ of this protein segment (Fig. 1b and c). As stated above, BMP15 is synthesized as a pre-proprotein. We hypothesize that insufficient processing of the signal peptide of BMP15-Ser5Arg can affect normal secretion of the protein and even induce a dominant negative effect. Although the involvement of some BMP15 variants in the aetiology of POF is unclear, the pathogenic character of other mutations is well documented (1,4 and references therein). The novel potentially pathogenic variant of BMP15 described here deserves further functional studies. Nevertheless, such assays are delicate as the production of bioactive recombinant BMP factors is particularly complex (5 and references therein).


Urology | 2011

Cytogenetic and molecular aspects of absolute teratozoospermia: comparison between polymorphic and monomorphic forms.

Sonia Brahem; Hatem Elghezal; Houda Ghédir; Hanène Landolsi; Abdelbacett Amara; Samira Ibala; Moez Gribaa; Ali Saad; Meriem Mehdi

OBJECTIVE To compare the results of cytogenetic and molecular analysis between absolute polymorphic and monomorphic teratozoospermia. METHODS The semen samples from patients with polymorphic teratozoospermia (n = 20), globozoospermia (n = 8), or macrocephalic sperm head syndrome (n = 12), and healthy fertile men (n = 20) were analyzed according to the World Health Organization criteria. The constitutional blood karyotype of the patients was performed on cultured lymphocytes, according to standard techniques. Microdeletion analysis of the Y chromosomes used a sequence tagged site-polymerase chain reaction technique. Triple-color fluorescent in situ hybridization for chromosomes X, Y, and 18 were used to analyze the meiotic segregation. DNA fragmentation was detected using the terminal desoxynucleotidyl transferase-mediated deoxyuridine triphosphate biotin nick-end labeling assay. RESULTS Whatever the type of teratozoospermia, a normal karyotype and an absence of Y chromosome microdeletion were shown for all patients. A significant increase in the sperm aneuploidy rate and DNA fragmentation were shown, regardless of the type of teratozoospermia. Spermatozoa of the patients with globozoospermia carry an abnormal chromosomal constitution and DNA damage rate with the same frequency as that found in the sperm of patients with absolute polymorphic teratozoospermia. However, a greater sperm aneuploidy rate and DNA fragmentation were found in patients whose teratozoospermia was mainly characterized by increased rates of spermatozoa with macrocephalic head and multiple flagella. CONCLUSION Our data have demonstrated that DNA fragmentation and sperm aneuploidy are critical tests in teratozoospermic men, because the results could negatively affect the intracytoplasmic sperm injection outcomes and might play an important role in the counseling of couples considering intracytoplasmic sperm injection.


Annales De Genetique | 2002

Cytogenetic analysis in 139 Tunisian patients with de novo acute myeloid leukemia.

Halima Sennana Sendi; Hatem Elghezal; Henda Temmi; Haifa Hichri; Moez Gribaa; Halima Elomri; Belkiss Meddeb; Tarek Ben Othmane; Moez Elloumi; Ali Saad

This paper presents the results of a cytogenetic analysis in 139 Tunisian patients with de novo acute myeloid leukemia (AML), including 27 children aged 1-15 years and 112 adults. Mean age was 32 (range 1-75) and the M/F ratio was 1.43. Of our patients, 45% had apparently normal karyotypes. Acquired chromosome aberrations were found in 77 (55% ) patients. t(8;21) was identified in 27 patients (19%); t(15;17) in 13 patients (9%); deletion 7q or monosomy 7 in seven patients (5%); +8 in seven patients (5%); abnormal 16 in four patients (3%); 11q23 rearrangements in two patients (2%) and del(5q), in one patient (1%). The remaining 16 patients had miscellaneous clonal abnormalities. Specific translocations associated with the FAB type were found: t(8;21) with AML2 and t(15;17) with AML3. We concluded that our study in a Tunisian population confirmed the relation between some specific abnormalities and the FAB classification. We found a higher incidence for t(8;21) than usually described.


Journal of Assisted Reproduction and Genetics | 2011

Chromosomal segregation in spermatozoa of five Robertsonian translocation carriers t(13;14)

Manel Mahjoub; Meriem Mehdi; Sonia Brahem; Hatem Elghezal; Samira Ibala; Ali Saad

PurposeTo analyse the segregation of a Robertsonian translocation t(13;14) in five male carriers, and to verify a possible inter-chromosomal effect (ICE) of the Robertsonian translocation on chromosomes 18, X, and Y.MethodsThe spermatozoa of these patients (n = 5) and of 15 donors with normal semen parameters and 46,XY karyotype were analysed using triple colour FISH with locus specific probes for chromosomes 13, 14, and 21 and by triple colour FISH for chromosomes X, Y, and 18.ResultsThe frequency of balanced spermatozoa resulting from alternate segregation varied between 62.16% and 81.70% with a mean of 71.5%. The rates of unbalanced spermatozoa resulting from adjacent segregation varied between 13.4% and 25.1% with a mean of 18.26%. Triple colour FISH X-Y-18 showed a significant increase in disomy frequencies of these chromosomes in comparison with controls, indicating an ICE.ConclusionIn spite of the high number of normal/balanced frequencies, there remain many unbalanced spermatozoa resulting from adjacent mode of segregation. This raises the question of the unbalanced chromosomal risk for the offspring of 45,XY, t(13;14) males and the importance of the genetic counselling prior to ICSI or IVF treatment for couples where the male is a Robertsonian translocation carrier.


International Journal of Occupational Medicine and Environmental Health | 2013

A cytogenetic approach to the effects of low levels of ionizing radiation (IR) on the exposed Tunisian hospital workers

Sana Bouraoui; Soumaya Mougou; Afef Drira; Faten Tabka; Nouha Bouali; Najib Mrizek; Hatem Elghezal; Ali Saad

ObjectivesThe aim of this study is to assess chromosomal damage in Tunisian hospital workers occupationally exposed to low levels of ionizing radiation (IR).Materials and MethodsThe cytokinesis-block micronucleus (CBMN) assay in the peripheral lymphocytes of 67 exposed workers compared to 43 controls matched for gender, age and smoking habits was used. The clastogenic/aneugenic effect of IR was evaluated using the CBMN assay in combination with fluorescence in situ hybridization with human pan-centromeric DNA in all the exposed subjects and controls.ResultsThe study showed a significant increase of the micronucleus (MN) frequency in the lymphocytes of the exposed workers compared to the control group (13.63±4.9‰ vs. 6.52±4.21‰, p < 0.05). The centromere analysis performed in our study showed that MNs in hospital staff were predominantly centromere negative (72%) and the mean negative labeled micronucleus (C-MN) frequency was significantly higher in the exposed subjects than in the controls (9.04±4.57‰ vs. 1.17±0.77‰). The multivariate regression analysis, taking into account all confounding factors, showed that only the time of exposure to IR had a significant effect on the level of MNs and C-MN.ConclusionThe present study shows that chromosomal damage leading to the formation of micronucleated lymphocytes is more frequent in the hospital workers exposed to IR than in the controls, despite the low levels of exposure. The results of the study confirm the well-known clastogenic properties of ionizing radiation. In regards to health monitoring, detection of early genotoxic effects may allow for the adoption of preventive biological control measures, such as hygienic improvements in the workplace or reduction of hours of occupational exposure.

Collaboration


Dive into the Hatem Elghezal's collaboration.

Top Co-Authors

Avatar

Ali Saad

University of Sousse

View shared research outputs
Top Co-Authors

Avatar

Sonia Brahem

University Teaching Hospital

View shared research outputs
Top Co-Authors

Avatar

Meriem Mehdi

University Teaching Hospital

View shared research outputs
Top Co-Authors

Avatar
Top Co-Authors

Avatar
Top Co-Authors

Avatar

Ali Saad

University of Sousse

View shared research outputs
Top Co-Authors

Avatar
Top Co-Authors

Avatar

Mounir Ajina

University Teaching Hospital

View shared research outputs
Top Co-Authors

Avatar

Samira Ibala

University Teaching Hospital

View shared research outputs
Top Co-Authors

Avatar
Researchain Logo
Decentralizing Knowledge