The Content of Thyroid Hormone Receptor α in Ewe Kisspeptin Neurones is not Season-Dependent.

Seasonal reproduction is grounded in several mechanisms, among which are plasticity in both hormone synthesis and neuronal networks. Increased daylength on long days (LD) translates into local tri-iodothyronin (T3) production in the mediobasal hypothalamus that will enable the transition to the anoestrus season in sheep. The photoperiod also strongly affects the content of kisspeptin (Kiss), a hypothalamic neuropeptide exerting a potent stimulatory effect on gonadotrophin-releasing hormone release. Our hypothesis was that T3 directly inhibits Kiss release during LD. Using double immunocytochemistry, we first searched for coexpression of thyroid hormone receptor (THR)α in Kiss neurones in ewes with an active or inactive gonadotrophic axis. In both the preoptic area and the arcuate nucleus, most Kiss neurones were labelled by THR antibody under both physiological/photoperiodic conditions. These results suggest thyroid hormones may affect Kiss synthesis and release all through the year. We then attempted to assess the influence of T3 on Kiss content in hypothalamic explants sampled from ewes with an active gonadotrophic axis. Kiss produced by hypothalamic explants cultured with different doses of T3 (300 or 600 pg) and subjected to different times of incubation (2 or 24 h) was measured. No significant effects of T3 on Kiss tissular content were observed for the two doses of T3 and for the two incubation times. In light of these findings, potential reasons for the divergent effects of thyroid hormones on Kiss content are discussed. Our data emphasise that the effects of thyroid hormone on Kiss synthesis are not one-sided and may affect a wide range of functions.

Association of GSTT1 non-null and NAT1 slow/rapid genotypes with von Hippel-Lindau tumour suppressor gene transversions in sporadic renal cell carcinoma.

The von Hippel-Lindau (VHL) tumour suppressor gene is commonly mutated in renal cell carcinoma of clear cell type (CCRCC). We investigated the possible relationship between VHL mutations in sporadic CCRCC and polymorphism of genes encoding enzymes involved in carcinogen metabolism: two cytochrome P450 monooxygenases (CYP1A1 and CYP2D6), one NAD[P]H:quinone oxidoreductase (NQO1), three glutathione S-transferases (GSTM1, GSTT1 and GSTP1) and two arylamine N-acetyltransferases (NAT1 and NAT2). We analysed DNA from tumour and nontumoural kidney tissue from 195 CCRCC patients. Single VHL mutations were identified in 88 patients and double mutations were present in two patients. Nine of 18 transversions were GC to TA, four were AT to TA, four were GC to CG and one was AT to CG. Ten of 19 transitions were GC to AT and nine were AT to GC. We also identified 53 frameshifts and two GC to AT at CpG. An excess of transversions was observed in a subset of patients with active GSTT1 [GSTT1 (+) genotype] and probably defective NAT1 (NAT1 S/R variant genotype). All 18 transversions were in GSTT1 (+) patients, whereas only 76% of transitions (P = 0.05) and 81% of the other mutations (P = 0.06) occurred in this genotype. We found that 28% of the transversions were in the NAT1 S/R genotype versus 12% of the transitions (P = 0.40) and 4% of the other mutations (P = 0.01). This suggests that pharmacogenetic polymorphisms may be associated with the type of acquired VHL mutation, which may modulate CCRCC development.

[Impact of reverse transcriptase inhibitors on sperm mitochondrial and genomic DNA in assisted reproduction techniques]. / Impact des inhibiteurs nucléosidiques de la transcriptase inverse sur l'ADN mitochondrial et génomique des spermatozoïdes lors de l'assistance médicale à la procréation.

For the last ten years, antiretroviral therapy (ARV) has improved the prognosis in HIV-1 infection and showed a better control of the viral excretion by reducing viral shedding in semen. However, nucleoside analogues reverse transcriptase inhibitors (NRTI) therapy reported important adverse effects. Most of these side effects observed seem to be linked with a common mechanism: mitochondrial activity alteration. Since the introduction of protocols for HIV-1 serodiscordant couples, with male infected partners under NRTI therapy, many results in the literature such as: semen characteristics and pregnancies, drew the attention of research teams. Many studies have suggested that NRTI has an affect on semen parameters, but proposed mechanisms of these effects have rarely been discussed. NRTI have a great affinity for the reverse transcriptase of HIV-1. Because many NRTI are not only inhibitors of reverse transcriptase but also inhibitors of the DNA polymerase beta and gamma, several toxic effects can be considered. Nevertheless, this specificity is not absolute and "accidental" incorporations of NRTI can occur on genomic sperm DNA. Only one study on genomic sperm DNA with patients under NRTI therapy was published without concluding results. Recently, studies have suggested that NRTI exposure could induce an alteration on mitochondrial energy-generating ability of spermatozoa. NRTI are known to induce an increase in the generation of reactive oxygen species, which results in the degradation of mitochondrial transmembrane potential (Deltapsim). This loss of Deltapsim can tend to release some specific apoptosis factors, such as cytochrome c, that initiates programmed cell death. Sperm DNA fragmentation, associated to apoptosis, was reported as a possible cause of recurrent pregnancy loss. If the incorporation of NRTI was reported in genomic DNA of somatic cells, the absence of data on the genomic sperm DNA justifies further studies concerning the effects of paternal exposure to NRTI on the genomic material of the male gamete, in particular because of its implication in the zygote development after fertilization.

1H and 13C chemical shifts for some tetrasubstituted 2,5-diaryl di- and tetrahydrofuran derivatives.

The 1H and 13C NMR chemical shifts of four 2,5-diaryltetrahydrofuran derivatives and their dihydro precursors were assigned completely with certainty using a concerted application of one- and two-dimensional experiments (DEPT, gs-COSY, gs-HMQC and gs-HMBC)

[Effects, on early auditory evoked potentials, of road traffic noise, of benzodiazepine and their combination]. / Effects, sur les potentiels évoqués auditifs précoces, d'un bruit de trafic routier, d'une benzodiazépine et de leur conjugaison.

In this study, 30 young men and 30 young women (with the same proportion of anxious persons in each group) were submitted, in random order, to: i) a road traffic noise of 75 dBA for 15 min; ii) this same noise for 15 min, having ingested 0.25 mg of alprazolam (Xanax*) 1 h before; iii) uniquely 0.25 mg of alprazolam. The auditory brainstem evoked potentials (ABEP) were taken before and after exposure to noise (for the non-noise case, we respected the same time schedule). The alprazolam had an effect on the cochlea and can be considered as a noise adaptation factor on the auditory pathways explored by the ABEP.