Lack of association between single polymorphic variants of the mitochondrial nicotinamide adenine dinucleotide dehydrogenase 3, and 4L (MT-ND3 and MT-ND4L) and male infertility

Male infertility is a multifactorial condition associated with different genetic abnormalities in at least 15%–30% of cases. The purpose of this study was to identify suspected correlations between infertility and polymorphisms in mitochondrial NADH dehydrogenase subunits 3 and 4L (MT-ND3 and MT-ND4L) in subfertile male spermatozoa. Sanger sequencing of the mitochondrial DNA target genes was performed on 68 subfertile and 44 fertile males. Eight single nucleotide polymorphisms (SNPs) in MT-ND3 (rs2853826, rs28435660, rs193302927, rs28358278, rs41467651, rs3899188, rs28358277 and rs28673954) and seven SNPs in MT-ND4L (rs28358280, rs28358281, rs28358279, rs2853487, rs2853488, rs193302933 and rs28532881) were detected and genotyped. The genotypes and allele frequencies of the study population have shown a lack of statistically significant association between MT-ND3 and MT-ND4L SNPs and male infertility. However, no statistically significant association was found between the asthenozoospermia, oligozoospermia, teratozoospermia, asthenoteratozoospermia, oligoasthenoteratozoospermia and oligoteratozoospermia subgroups of subfertile males. However, rs28358278 genotype of the MT-ND3 gene was reported in the subfertile group but not in the fertile group, which implies a possible role of this SNP in male infertility. In conclusion, the investigated polymorphic variants in the MT-ND3 and MT-ND4L genes did not show any significant association with the occurrence of male infertility. Further studies are required to evaluate these findings. Moreover, the subfertile individuals who exhibit a polymorphism at rs28358278 require further monitoring and evaluation.     

Ex vivo immunomodulatory effect of all-trans-retinoic acid during Behçet’s disease: a study in Algerian patients

Uveitis, recurrent oral and genital ulcerations associated with skin lesions are the major symptoms of a chronic multisystemic inflammatory disorder known as Behçet’s disease (BD). High prevalence of this dreaded disease has been observed in the Mediterranean basin, including Algeria and along the Silk Road. Although the etiologic agent of this disease remains uncertain, many hypotheses have been advanced in its pathogenesis. Our team has previously reported high levels of nitric oxide (NO) in sera of BD patients, suggesting its deleterious effect during chronic inflammation. In our current study, the aim is to investigate the ex vivo immunomodulatory effect of all-trans-retinoic acid (ATRA) on NO pathway in Algerian BD patients. First, peripheral blood mononuclear cells isolated from active and inactive BD patients and healthy controls were cultured with different concentrations of ATRA. NO production was estimated with the Griess method. To elucidate the underlying mechanisms of ATRA effect on NO production, we analyze inducible nitric oxide synthase expression and nuclear factor-κB (NF-κB) activity by immunofluorescence test. Our results revealed a higher production of NO in active BD compared with the inactive stage and healthy controls. We observed that ATRA inhibits NO production in BD both in active and inactive stages and inhibits NF-κB translocation. In conclusion, we report a relationship between NO production and the disease activity. ATRA down-regulates NO production in BD patients. This immunomodulatory effect seems to be mediated through NF-κB pathway. All these findings suggest that ATRA could be considered as a promising therapy for BD.     

A new mutation identified in <Emphasis Type="Italic">SPATA16</Emphasis> in two globozoospermic patients

Purpose

The aim of this study is to identify potential genes involved in human globozoopsermia.

Methods

Nineteen globozoospermic patients (previously screened for DPY19L2 mutations with no causative mutation) were recruited in this study and screened for mutations in genes implicated in human globozoospermia SPATA16 and PICK1. Using the candidate gene approach and the determination of Spata16 partners by Glutathione S-transferase (GST) pull-down four genes were also selected and screened for mutations.

Results

We identified a novel mutation of SPATA16: deletion of 22.6 Kb encompassing the first coding exon in two unrelated Tunisian patients who presented the same deletion breakpoints. The two patients shared the same haplotype, suggesting a possible ancestral founder effect for this new deletion. Four genes were selected using the candidate gene approach and the GST pull-down (GOPC, PICK1, AGFG1 and IRGC) and were screened for mutation, but no variation was identified.

Conclusions

The present study confirms the pathogenicity of the SPATA16 mutations. The fact that no variation was detected in the coding sequence of AFGF1, GOPC, PICK1 and IRGC does not mean that they are not involved in human globozoospermia. A larger globozoospermic cohort must be studied in order to accelerate the process of identifying new genes involved in such phenotypes. Until sufficient numbers of patients have been screened, AFGF1, GOPC, PICK1 and IRGC should still be considered as candidate genes.

     

Influence of parity on bone mineral density and peripheral fracture risk in Moroccan postmenopausal women

The aims of the study were to determine: (1) the relationship between parity and bone mineral density (BMD); (2) the relationship between parity and osteoporotic peripheral fractures.

Material and methods

The group studied included 730 postmenopausal women. Patients were separated into four groups according to the number of fullterm pregnancies, group 1: nulliparae, group 2: one to three pregnancies, group 3: four to five pregnancies, and group 4: six and more pregnancies. Additionally, patients were separated into three groups according to their ages, as <50 years, 50–59 years and ≥60 years.

Results

The median parity was 4 [0–20]. All the patients with parity greater than six had spine and hip BMD values significantly lower than values in the other groups (p < 0.001). After adjustment for age and body mass index (BMI), decreased lumbar and total hip BMD were still associated to increased parity (analysis of covariance (ANCOVA), p = 0.04 and 0.023, respectively). The relation between parity and lumbar BMD was highly significant among women aged <50 years (age-adjusted p = 0.022), while there was no parity-spine BMD association in the other age groups. The relation between parity and hip BMD was seen only in the group 50–59 years (age-adjusted p = 0.042). A positive history for peripheral fractures was present in 170 (23%) patients. There was relationship between parity and peripheral fractures neither in the whole population nor in the sub-groups according to age.

Discussion

The present study suggests that the BMD of the spine and hip decreases with an increasing number of pregnancies, and this situation shows variations in different age groups. However, there was no correlation between parity level and peripheral fractures.     

Parainfluenza virus‐3‐induced cytopathic effects on lung tissue and bronchoalveolar lavage fluid in a bone marrow transplant recipient

Parainfluenza virus type 3(PIV‐3) commonly causes respiratory tract infections in hematopoietic stem cell transplant (HSCT) patients. The majority of PIV‐3 infections develop in patients who have undergone stem cell transplantation from unrelated donors. From these patients, bronchoalveolar lavage (BAL) fluid and/or lung biopsies are often collected and sent for evaluation of infectious processes. However, cytologic findings associated with a PIV‐3 infection in BAL fluid have not been reported in the literature. We describe BAL cytology and lung biopsy findings in a patient who received an HSCT from a related donor and subsequently developed a PIV‐3 infection. This patient was noted to have scattered reticular‐nodular opacities in both lungs on computed tomogram scan and underwent transbronchial biopsy and BAL of the left lower lobe. Examination of the BAL fluid revealed scattered multinucleated giant cells intermixed with inflammatory cells. The lung biopsy showed organizing pneumonia associated with several multinucleated respiratory epithelial cells containing rare intracytoplasmic inclusions. Gram, periodic acid Schiff, Gomori methenamine silver, and acid fast stains on the biopsy specimen failed to reveal microorganisms. A sample of the BAL fluid sent for respiratory viral culture grew PIV‐3. These findings suggest that the presence of giant cells in transplant patients with organizing pneumonia should raise suspicion of a PIV‐3 infection. Diagn. Cytopathol. 2014;42:521–524. © 2013 Wiley Periodicals, Inc.