Roles of mitogen-activated protein kinases and angiotensin II in renal development

Experimental and clinical evidence suggests that angiotensin II (AII) participates in renal development. Renal AII content is several-fold higher in newborn rats and mice than in adult animals. AII receptors are also expressed in higher amounts in the kidneys of newborn rats. The kidneys of fetuses whose mother received a type 1 AII receptor (AT1) antagonist during gestation present several morphological alterations. Mutations in genes that encode components of the renin-angiotensin system are associated with autosomal recessive renal tubular dysgenesis. Morphological changes were detected in the kidneys of 3-week-old angiotensin-deficient mice. Mitogen-activated protein kinases (MAPKs) are important mediators that transduce extracellular stimuli to intracellular responses. The MAPK family comprises three major subgroups, namely extracellular signal-regulated protein kinase (ERK), c-jun N-terminal kinases (JNK), and p38 MAPK (p38). Important events in renal growth during nephrogenesis such as cellular proliferation and differentiation accompanied by apoptosis on a large scale can be mediated by MAPK pathways. A decrease in glomerulus number was observed in embryos cultured for 48 and 120 h with ERK or p38 inhibitors. Many effects of AII are mediated by MAPK pathways. Treatment with losartan during lactation provoked changes in renal function and structure associated with alterations in AT1 and type 2 AII (AT2) receptors and p-JNK and p-p38 expression in the kidney. Several studies have shown that AII and MAPKs play an important role in renal development. However, the relationship between the effects of AII and MAPK activation on renal development is still unclear.

Normal flow-mediated vasodilatation of the brachial artery and carotid artery intima-media thickness in subclinical hypothyroidism

Subclinical hypothyroidism (SHT) is a disease for which exact therapeutic approaches have not yet been established. Previous studies have suggested an association between SHT and coronary heart disease. Whether this association is related to SHT-induced changes in serum lipid levels or to endothelial dysfunction is unclear. The aim of this study was to determine endothelial function measured by the flow-mediated vasodilatation of the brachial artery and the carotid artery intima-media thickness (IMT) in a group of women with SHT compared with euthyroid subjects. Triglycerides, total cholesterol, HDL-C, LDL-C, apoprotein A (apo A), apo B, and lipoprotein(a) were also determined. Twenty-one patients with SHT (mean age: 42.4 ± 10.8 years and mean thyroid-stimulating hormone (TSH) levels: 8.2 ± 2.7 µIU/mL) and 21 euthyroid controls matched for body mass index, age and atherosclerotic risk factors (mean age: 44.2 ± 8.5 years and mean TSH levels: 1.4 ± 0.6 µIU/mL) participated in the study. Lipid parameters (except HDL-C and apo A, which were lower) and IMT values were higher in the common carotid and carotid bifurcation of SHT patients with positive serum thyroid peroxidase antibodies (TPO-Ab) (0.62 ± 0.2 and 0.62 ± 0.16 mm for the common carotid and carotid bifurcation, respectively) when compared with the negative TPO-Ab group (0.55 ± 0.24 and 0.58 ± 0.13 mm, for common carotid and carotid bifurcation, respectively). The difference was not statistically significant. We conclude that minimal thyroid dysfunction had no adverse effects on endothelial function in the population studied. Further investigation is warranted to assess whether subclinical hypothyroidism, with and without TPO-Ab-positive serology, has any effect on endothelial function.

Association of CYP7A1 -278A>C polymorphism and the response of plasma triglyceride after dietary intervention in dyslipidemic patients

We investigated the effect of the -278A>C polymorphism in the CYP7A1 gene on the response of plasma lipids to a reduced-fat diet for 6 to 8 weeks in a group of 82 dyslipidemic males with a mean age of 46.0 ± 11.7 years. Individuals who presented at least one high alteration in total cholesterol, low-density lipoprotein cholesterol or triglyceride values were considered to be dyslipidemic. Exclusion criteria were secondary dyslipidemia due to diabetes mellitus, renal, liver, or thyroid disease. None of the subjects were using lipid-lowering medication. Baseline and follow-up lipid concentrations were measured. The genotypes were determined by the digestion of PCR products with the BsaI restriction endonuclease. There were statistically significant reductions in plasma total cholesterol, low-density lipoprotein cholesterol and triglyceride concentrations after dietary intervention. The minor allele C has a frequency of 43%. Carriers of the C allele had significantly lower triglyceride concentrations (P = 0.02) than AA homozygotes. After adjustment of covariates, subjects with the AC and CC genotypes showed a greater reduction in triglyceride concentrations compared to subjects with the AA genotype. Multiple linear regression analyses showed that the AC and CC CYP7A1 genotypes accounted for 5.2 and 6.2% of triglyceride concentration during follow-up and adjusted percent of change of triglyceride concentration, respectively. The present study provides evidence that -278A>C polymorphism in the CYP7A1 gene can modify triglyceride concentrations in response to a reduced fat diet in a dyslipidemic male population. This gene represents a potential locus for a nutrigenetic directed approach.

Radioiodine plus recombinant human thyrotropin do not cause acute airway compression and are effective in reducing multinodular goiter

Recombinant human thyrotropin (rhTSH) reduces the activity of radioiodine required to treat multinodular goiter (MNG), but acute airway compression can be a life-threatening complication. In this prospective, randomized, double-blind, placebo-controlled study, we assessed the efficacy and safety (including airway compression) of different doses of rhTSH associated with a fixed activity of 131I for treating MNG. Euthyroid patients with MNG (69.3 ± 62.0 mL, 20 females, 2 males, 64 ± 7 years) received 0.1 mg (group I, N = 8) or 0.01 mg (group II, N = 6) rhTSH or placebo (group III, N = 8), 24 h before 1.11 GBq 131I. Radioactive iodine uptake was determined at baseline and 24 h after rhTSH and thyroid volume (TV, baseline and 6 and 12 months after treatment) and tracheal cross-sectional area (TCA, baseline and 2, 7, 180, and 360 days after rhTSH) were determined by magnetic resonance; antithyroid antibodies and thyroid hormones were determined at frequent intervals. After 6 months, TV decreased significantly in groups I (28.5 ± 17.6%) and II (21.6 ± 17.8%), but not in group III (2.7 ± 15.3%). After 12 months, TV decreased significantly in groups I (36.7 ± 18.1%) and II (37.4 ± 27.1%), but not in group III (19.0 ± 24.3%). No significant changes in TCA were observed. T3 and free T4 increased transiently during the first month. After 12 months, 7 patients were hypothyroid (N = 3 in group I and N = 2 in groups II and III). rhTSH plus a 1.11-GBq fixed 131I activity did not cause acute or chronic changes in TCA. After 6 and 12 months, TV reduction was more pronounced among patients treated with rhTSH plus 131I.

Effect of hormone replacement on exercise cardiopulmonary reserve and recovery performance in subclinical hypothyroidism

Subclinical hypothyroidism (SH) patients present cardiopulmonary, vascular and muscle dysfunction, but there is no consensus about the benefits of levothyroxine (L-T4) intervention on cardiopulmonary performance during exercise. The aim of the present study was to investigate the effects of L-T4 on cardiopulmonary exercise reserve and recovery in SH patients. Twenty-three SH women, 44 (40-50) years old, were submitted to two ergospirometry tests, with an interval of 6 months of normalization of thyroid-stimulating hormone (TSH) levels (L-T4 replacement group) or simple observation (TSH = 6.90 μIU/mL; L-T4 = 1.02 ng/dL). Patients with TSH >10 μIU/mL were excluded from the study to assure that they would receive treatment in this later stage of SH. Twenty 30- to 57-year-old women with no thyroid dysfunction (TSH = 1.38 μIU/mL; L-T4 = 1.18 ng/dL) were also evaluated. At baseline, lower values of gas exchange ratio reserve (0.24 vs 0.30; P < 0.05) were found for SH patients. The treated group presented greater variation than the untreated group for pulmonary ventilation reserve (20.45 to 21.60 L/min; median variation = 5.2 vs 25.09 to 22.45 L/min; median variation = -4.75, respectively) and for gas exchange ratio reserve (0.19 to 0.27; median variation = 0.06 vs 0.28 to 0.18; median variation = -0.08, respectively). There were no relevant differences in cardiopulmonary recovery for either group at baseline or after follow-up. In the sample studied, L-T4 replacement improved exercise cardiopulmonary reserve, but no modification was found in recovery performance after exercise during this period of analysis.

The novel p.E89K mutation in the SRY gene inhibits DNA binding and causes the 46,XY disorder of sex development

Male sex determination in humans is controlled by the SRY gene, which encodes a transcriptional regulator containing a conserved high mobility group box domain (HMG-box) required for DNA binding. Mutations in the SRY HMG-box affect protein function, causing sex reversal phenotypes. In the present study, we describe a 19-year-old female presenting 46,XY karyotype with hypogonadism and primary amenorrhea that led to the diagnosis of 46,XY complete gonadal dysgenesis. The novel p.E89K missense mutation in the SRY HMG-box was identified as a de novo mutation. Electrophoretic mobility shift assays showed that p.E89K almost completely abolished SRY DNA-binding activity, suggesting that it is the cause of SRY function impairment. In addition, we report the occurrence of the p.G95R mutation in a 46,XY female with complete gonadal dysgenesis. According to the three-dimensional structure of the human SRY HMG-box, the substitution of the conserved glutamic acid residue by the basic lysine at position 89 introduces an extra positive charge adjacent to and between the positively charged residues R86 and K92, important for stabilizing the HMG-box helix 2 with DNA. Thus, we propose that an electrostatic repulsion caused by the proximity of these positive charges could destabilize the tip of helix 2, abrogating DNA interaction.

Effect of triiodothyronine on the maxilla and masseter muscles of the rat stomatognathic system

The maxilla and masseter muscles are components of the stomatognathic system involved in chewing, which is frequently affected by physical forces such as gravity, and by dental, orthodontic and orthopedic procedures. Thyroid hormones (TH) are known to regulate the expression of genes that control bone mass and the oxidative properties of muscles; however, little is known about the effects of TH on the stomatognathic system. This study investigated this issue by evaluating: i) osteoprotegerin (OPG) and osteopontine (OPN) mRNA expression in the maxilla and ii) myoglobin (Mb) mRNA and protein expression, as well as fiber composition of the masseter. Male Wistar rats (~250 g) were divided into thyroidectomized (Tx) and sham-operated (SO) groups (N = 24/group) treated with T3 or saline (0.9%) for 15 days. Thyroidectomy increased OPG (~40%) and OPN (~75%) mRNA expression, while T3 treatment reduced OPG (~40%) and OPN (~75%) in Tx, and both (~50%) in SO rats. Masseter Mb mRNA expression and fiber type composition remained unchanged, despite the induction of hypo- and hyperthyroidism. However, Mb content was decreased in Tx rats even after T3 treatment. Since OPG and OPN are key proteins involved in the osteoclastogenesis inhibition and bone mineralization, respectively, and that Mb functions as a muscle store of O2 allowing muscles to be more resistant to fatigue, the present data indicate that TH also interfere with maxilla remodeling and the oxidative properties of the masseter, influencing the function of the stomatognathic system, which may require attention during dental, orthodontic and orthopedic procedures in patients with thyroid diseases.

Hypothyroidism decreases proinsulin gene expression and the attachment of its mRNA and eEF1A protein to the actin cytoskeleton of INS-1E cells

The actions of thyroid hormone (TH) on pancreatic beta cells have not been thoroughly explored, with current knowledge being limited to the modulation of insulin secretion in response to glucose, and beta cell viability by regulation of pro-mitotic and pro-apoptotic factors. Therefore, the effects of TH on proinsulin gene expression are not known. This led us to measure: a) proinsulin mRNA expression, b) proinsulin transcripts and eEF1A protein binding to the actin cytoskeleton, c) actin cytoskeleton arrangement, and d) proinsulin mRNA poly(A) tail length modulation in INS-1E cells cultured in different media containing: i) normal fetal bovine serum - FBS (control); ii) normal FBS plus 1 µM or 10 nM T3, for 12 h, and iii) FBS depleted of TH for 24 h (Tx). A decrease in proinsulin mRNA content and attachment to the cytoskeleton were observed in hypothyroid (Tx) beta cells. The amount of eEF1A protein anchored to the cytoskeleton was also reduced in hypothyroidism, and it is worth mentioning that eEF1A is essential to attach transcripts to the cytoskeleton, which might modulate their stability and rate of translation. Proinsulin poly(A) tail length and cytoskeleton arrangement remained unchanged in hypothyroidism. T3 treatment of control cells for 12 h did not induce any changes in the parameters studied. The data indicate that TH is important for proinsulin mRNA expression and translation, since its total amount and attachment to the cytoskeleton are decreased in hypothyroid beta cells, providing evidence that effects of TH on carbohydrate metabolism also include the control of proinsulin gene expression.

The increased but non-predominant expression of Th17- and Th1-specific cytokines in Hashimoto’s thyroiditis but not in Graves’ disease

Hashimoto’s thyroiditis (HT) is considered to be mediated mainly by Th1 cells, but it is not known whether Graves’ disease (GD) is associated with Th1 or Th2 predominance. Th17 cells, a novel subset of Th cells, play a crucial role in the pathogenesis of various autoimmune disorders. In the present study, the expression of IL-17A and IFN-γ was investigated in patients with HT or GD. mRNA expression of IL-17A and IFN-γ in peripheral blood mononuclear cells (PBMC) from 43 patients with autoimmune thyroid disease (AITD) and in thyroid tissues from 40 AITD patients were measured by real-time qRT-PCR. The protein expression of IL-17A and IL-23p19 was examined by immunohistochemistry in thyroid tissues from 28 AITD patients. The mRNA levels of IL-17A and IFN-γ were higher in both PBMC and thyroid tissues of HT patients than in controls (mRNA levels are reported as the cytokine/β-actin ratio: IL-17 = 13.58- and 2.88-fold change and IFN-γ = 16.54- and 2.74-fold change, respectively, P < 0.05). Also, the mRNA levels of IL-17A and IFN-γ did not differ significantly in GD patients (P > 0.05). The high protein expression of IL-17A (IOD = 15.17 ± 4.8) and IL-23p19 (IOD = 16.84 ± 7.87) in HT was confirmed by immunohistochemistry (P < 0.05). The similar high levels of IL-17A and IFN-γ suggest a mixed response of Th17 and Th1 in HT, where both cells may play important roles in the destruction procedure by cell-mediated cytotoxicity.

Performance assessment of the single photon emission microscope: high spatial resolution SPECT imaging of small animal organs

The single photon emission microscope (SPEM) is an instrument developed to obtain high spatial resolution single photon emission computed tomography (SPECT) images of small structures inside the mouse brain. SPEM consists of two independent imaging devices, which combine a multipinhole collimator, a high-resolution, thallium-doped cesium iodide [CsI(Tl)] columnar scintillator, a demagnifying/intensifier tube, and an electron-multiplying charge-coupling device (CCD). Collimators have 300- and 450-µm diameter pinholes on tungsten slabs, in hexagonal arrays of 19 and 7 holes. Projection data are acquired in a photon-counting strategy, where CCD frames are stored at 50 frames per second, with a radius of rotation of 35 mm and magnification factor of one. The image reconstruction software tool is based on the maximum likelihood algorithm. Our aim was to evaluate the spatial resolution and sensitivity attainable with the seven-pinhole imaging device, together with the linearity for quantification on the tomographic images, and to test the instrument in obtaining tomographic images of different mouse organs. A spatial resolution better than 500 µm and a sensitivity of 21.6 counts·s-1·MBq-1 were reached, as well as a correlation coefficient between activity and intensity better than 0.99, when imaging 99mTc sources. Images of the thyroid, heart, lungs, and bones of mice were registered using 99mTc-labeled radiopharmaceuticals in times appropriate for routine preclinical experimentation of <1 h per projection data set. Detailed experimental protocols and images of the aforementioned organs are shown. We plan to extend the instrument's field of view to fix larger animals and to combine data from both detectors to reduce the acquisition time or applied activity.

Neonatal hyper- and hypothyroidism alter the myoglobin gene expression program in adulthood

Myoglobin acts as an oxygen store and a reactive oxygen species acceptor in muscles. We examined myoglobin mRNA in rat cardiac ventricle and skeletal muscles during the first 42 days of life and the impact of transient neonatal hypo- and hyperthyroidism on the myoglobin gene expression pattern. Cardiac ventricle and skeletal muscles of Wistar rats at 7-42 days of life were quickly removed, and myoglobin mRNA was determined by Northern blot analysis. Rats were treated with propylthiouracil (5-10 mg/100 g) and triiodothyronine (0.5-50 µg/100 g) for 5, 15, or 30 days after birth to induce hypo- and hyperthyroidism and euthanized either just after treatment or at 90 days. During postnatal (P) days 7-28, the ventricle myoglobin mRNA remained unchanged, but it gradually increased in skeletal muscle (12-fold). Triiodothyronine treatment, from days P0-P5, increased the skeletal muscle myoglobin mRNA 1.5- to 4.5-fold; a 2.5-fold increase was observed in ventricle muscle, but only when triiodothyronine treatment was extended to day P15. Conversely, hypothyroidism at P5 markedly decreased (60%) ventricular myoglobin mRNA. Moreover, transient hyperthyroidism in the neonatal period increased ventricle myoglobin mRNA (2-fold), and decreased heart rate (5%), fast muscle myoglobin mRNA (30%) and body weight (20%) in adulthood. Transient hypothyroidism in the neonatal period also permanently decreased fast muscle myoglobin mRNA (30%) and body weight (14%). These results indicated that changes in triiodothyronine supply in the neonatal period alter the myoglobin expression program in ventricle and skeletal muscle, leading to specific physiological repercussions and alterations in other parameters in adulthood.

Novel cancer-related regulatory targets for the signalling sphingolipids sphingosine-1-phosphate and sphingosylphosphorylcholine

The signalling sphingolipid sphingosine-1-phosphate (S1P) is necessary for development of the immune system and vasculature and on a cellular level regulates migration, proliferation and survival. Due to these traits S1P has an important role in cancer biology. It is considered a primarily cancer-promoting factor and the enzyme which produces it, sphingosine kinase (SphK), is often over-expressed in tumours. S1P is naturally present in the blood, lymph, tissue fluids and cell cytoplasm and functions through its cell surface receptors (S1P1-5) and as an intracellular second messenger. Sphingosylphosphorylcholine (SPC) is closely related to S1P and has similar regulatory functions but has not been extensively studied. Both S1P and SPC are able to evoke either stimulatory or inhibitory effects on cancer cells depending on the context. The aim of this thesis work was to study novel regulatory targets of S1P and SPC, which mediate the effects of S1P/SPC signalling on cancer cell behaviour. The investigated targets are the transcription factor hypoxia-inducible factor 1 (HIF-1), the intermediate filament protein vimentin and components of the Hippo signalling pathway. HIF-1 has a central role in cancer biology, as it regulates a multitude of cancer-related genes and is potently activated by intratumoural hypoxia through stabilization of the regulatory subunit HIF-1α. Tumours typically harbour high HIF-1α levels and HIF-1, in turn, facilitates tumour angiogenesis and metastasis and regulates cancer cell metabolism. We found S1P to induce follicular thyroid cancer cell migration in normal oxygen conditions by increasing HIF-1α synthesis and stability and subsequently HIF-1 activity. Vimentin is a central regulator of cell motility and is also commonly over-expressed in cancers. Vimentin filaments form a cytoskeletal network in mesenchymal cells as well as epithelial cancer cells which have gone through epithelial-mesenchymal transition (EMT). Vimentin is heavily involved in cancer cell invasion and gives tumours metastatic potential. We saw both S1P and SPC induce phosphorylation of vimentin monomers and reorganization of the vimentin filament network in breast and anaplastic thyroid cancer cells. We also found vimentin to mediate the anti-migratory effect of S1P/SPC on these cells. The Hippo pathway is a novel signalling cascade which controls cancer-related processes such as cellular proliferation and survival in response to various extracellular signals. The core of the pathway consists of the transcriptional regulators YAP and TAZ, which activate predominantly cancer-promoting genes, and the tumour suppressive kinases Lats1 and Lats2 which inhibit YAP/TAZ. Increased YAP expression and activity has been reported for a wide variety of cancers. We found SPC to regulate Hippo signalling in breast cancer cells in a two-fold manner through effects on phosphorylation status, activity and/or expression of YAP and Lats2. In conclusion, this thesis reveals new details of the signalling function of S1P and SPC and regulation of the central oncogenic factors HIF-1 and vimentin as well as the novel cancer-related pathway Hippo.

Transport d’iode par le transporteur de sodium/acide monocarboxylique SMCT1

Le transporteur de Na+/ acide monocarboxylique sensible à l’ibuprofène (SMCT1) est exprimé dans la membrane apicale de plusieurs épithélia. Son rôle physiologique dans la glande thyroïde reste cependant obscur mais on présume qu’il pourrait agir comme un transporteur apical d’iode nécessaire pour la synthèse des hormones thyroïdiennes. Récemment, on a montré que SMCT1 possède un courant de fuite anionique sensible à [Na+]e qui permettrait de transporter l’iode de façon électrogénique. Cependant, un efflux d’iode sensible à l’ibuprofène, mais indépendant de la [Na+]e a été aussi observé sur des cultures primaires des thyrocytes porcins, suggérant un autre mécanisme de transport d’iode par SMCT1. Ce travail vise à comprendre les caractéristiques de ce genre de transport en utilisant comme modèle d’expression les ovocytes de Xenopus laevis. Les résultats obtenus des essais de captation d’iode radioactif montrent que SMCT1 présente un transport d’iode sensible à l’ibuprofène de l’ordre de 30nmol/ovocyte/h. Si ce transport est non saturable en iode (0-100 mM), il nécessite du Na+ dans la solution externe. En effet, le remplacement du Na+ extracellulaire par le NMDG inhibe complètement le transport. En outre, on s’est intéressé à exclure la possibilité de différents artefacts. En ayant trouvé que la grande majorité de l’iode radioactif se trouve dans la partie soluble de l’ovocyte, on exclut une liaison non spécifique de l’iode à la membrane cellulaire. Cependant, une bonne proportion de l’iode transporté pourrait être liée à des protéines à l’intérieur de l`ovocyte. En effet, on observe une réduction du transport d’iode dans les ovocytes exprimant SMCT1 de 81,6 ± 2 % en présence de 2 % BSA dans la solution extracellulaire. Également, on écarte la possibilité que le transport d’iode soit le résultat de la surexpression de protéines de transport endogènes dont les canaux chlore. Le transport d’iode semble spécifique à l’expression de SMCT1 et de manière intéressante à l’expression d’un autre transporteur de monocarboxylates, MCT1. L’analyse de l’ensemble des essais, y compris le fait que l’amplitude du transport observé est 20 fois plus grande que celle du courant de fuite nous mène à proposer que SMCT1 puisse transporter l’iode de façon électroneutre. Cependant, le mécanisme par lequel ceci est accompli n’est pas évident à identifier. L’utilisation d’un autre modèle cellulaire serait surement utile pour répondre à cette question.

Régions de susceptibilité dans les remaniements du chromosome Y et mosaïcisme : facteurs de risque du développement sexuel anormal

Le développement sexuel est un processus complexe qui dépend de nombreux gènes, une mutation pouvant entraîner un développement sexuel anormal. Par ailleurs, des anomalies chromosomiques peuvent avoir des répercussions importantes sur la détermination gonadique, surtout lorsqu'il s'agit du chromosome Y puisqu'il porte le gène clé du développement sexuel masculin. Premièrement, nous avons identifié par cytogénétique moléculaire le point de cassure chez 5 patients avec une translocation X;Y et 10 patients avec un chromosome Y isodicentrique. Nous avons ainsi démontré que certaines régions sont plus à risque d'être remaniées, notamment lorsqu'elles contiennent des palindromes ou d'autres séquences répétées. Nous avons également établi une relation entre la distance séparant le centromère et le point de cassure et l'instabilité des chromosomes Y isodicentriques lors des divisions cellulaires. Deuxièmement, nous avons étudié en cytogénétique les gonades de 22 patients avec un chromosome Y normal ou remanié et présentant un développement sexuel anormal. Nous avons mis en évidence la perte du chromosome Y remanié dans une majorité de cellules gonadiques des 10 patients étudiés, expliquant leur phénotype sexuel anormal. Cependant, chez 11 des 12 patients avec un chromosome Y normal, aucun mosaïcisme expliquant clairement leur détermination gonadique anormale n'a été retrouvé. Finalement, nous avons analysé par immunohistochimie les gonades dysgénésiques de 30 patients avec une anomalie du développement sexuel et un chromosome Y normal ou remanié. Nos travaux ont montré la présence de cellules germinales immatures au sein de cordons sexuels primitifs sous forme de tissu gonadique indifférencié dans 15 gonades, dont 9 ont évolué en tumeur gonadique. Dans 13 autres gonades, ces cellules germinales immatures avaient disparues par apoptose. Dans l'ensemble, notre recherche met en évidence la susceptibilité du chromosome Y à subir des remaniements et à être instable lors des divisions cellulaires, et indique que le mosaïcisme peut avoir des répercussions sur la détermination gonadique. Nos travaux montrent également que le tissu gonadique indifférencié peut évoluer vers deux entités, une tumeur gonadique ou une bandelette suite à l'apoptose des cellules germinales, mettant en lumière la nécessité d'analyser le tissu gonadique des patients XY avec dysgénésie gonadique dont les gonades sont laissées en place.

Le double fardeau de la malnutrition à l’âge scolaire en milieu urbain : une étude au Burkina Faso

Ce travail financé par l'ACDI a été réalisé au Laboratoire TRANSNUT de l'Université de Montréal (Canada)en collaboration avec le Laboratoire National de Santé Publique (Burkina Faso) et HKI-Burkina Faso.