Design and first evaluation of a sleep characterization monitoring system using remote contactless sensor.

This paper presents the design and a first evaluation of a new monitoring system based on contactless sensors to estimate sleep quality. This sensor produces thermal signals which have been used, at first, to detect a human presence in the bed and then to estimate sleep quality. To distinguish between different sleep phases, we have used methods of signal processing in order to extract the necessary features for learning an adapted statistical model. The existing monitoring systems use sensors attached to the bed or worn by the person. We propose in this paper a system based on a passive thermal sensor which has the advantage of being fixed on the wall, thus it is easier to use and more reliable. We explain different signal processing steps and describe sleep stage recognition algorithms. We propose an adaptation of the SAX method for the thermal signal. Finally, we evaluate our system in comparison with a polysomnographic recording system in the Hospital (CHU) of Limoges.

Expression of dominant-negative thyroid hormone receptor alpha1 in Leydig and Sertoli cells demonstrates no additional defect compared with expression in Sertoli cells only.

BACKGROUND: In the testis, thyroid hormone (T3) regulates the number of gametes produced through its action on Sertoli cell proliferation. However, the role of T3 in the regulation of steroidogenesis is still controversial. METHODS: The TRαAMI knock-in allele allows the generation of transgenic mice expressing a dominant-negative TRα1 (thyroid receptor α1) isoform restricted to specific target cells after Cre-loxP recombination. Here, we introduced this mutant allele in both Sertoli and Leydig cells using a novel aromatase-iCre (ARO-iCre) line that expresses Cre recombinase under control of the human Cyp19(IIa)/aromatase promoter. FINDINGS: We showed that loxP recombination induced by this ARO-iCre is restricted to male and female gonads, and is effective in Sertoli and Leydig cells, but not in germ cells. We compared this model with the previous introduction of TRαAMI specifically in Sertoli cells in order to investigate T3 regulation of steroidogenesis. We demonstrated that TRαAMI-ARO males exhibited increased testis weight, increased sperm reserve in adulthood correlated to an increased proliferative index at P3 in vivo, and a loss of T3-response in vitro. Nevertheless, TRαAMI-ARO males showed normal fertility. This phenotype is similar to TRαAMI-SC males. Importantly, plasma testosterone and luteinizing hormone levels, as well as mRNA levels of steroidogenesis enzymes StAR, Cyp11a1 and Cyp17a1 were not affected in TRαAMI-ARO. CONCLUSIONS/SIGNIFICANCE: We concluded that the presence of a mutant TRαAMI allele in both Leydig and Sertoli cells does not accentuate the phenotype in comparison with its presence in Sertoli cells only. This suggests that direct T3 regulation of steroidogenesis through TRα1 is moderate in Leydig cells, and that Sertoli cells are the main target of T3 action in the testis.

Direct and indirect consequences on gene expression of a thyroid hormone receptor alpha 1 mutation restricted to Sertoli cells.

Thyroid hormone is required for the timely transition of Sertoli cells from proliferative to differentiating and maturing. This transition takes place during a critical developmental period in mammals, which in mice is the first post-natal week. In order to identify the underlying molecular mechanisms of this differentiation process, we used Cre/loxP technology to selectively block the function of the thyroid hormone receptor TRα1 in Sertoli cells. We then used RNA-seq to analyze the changes in gene expression induced in the post-natal testis. This differential analysis provides genetic clues to the initial testicular defects resulting from disrupted thyroid hormone signaling, and suggests that Sertoli cells influence germ cells soon after their birth.

Depletion of the p43 mitochondrial T3 receptor increases Sertoli cell proliferation in mice.

Among T3 receptors, TRα1 is ubiquitous and its deletion or a specific expression of a dominant-negative TRα1 isoform in Sertoli cell leads to an increase in testis weight and sperm production. The identification of a 43-kDa truncated form of the nuclear receptor TRα1 (p43) in the mitochondrial matrix led us to test the hypothesis that this mitochondrial transcription factor could regulate Sertoli cell proliferation. Here we report that p43 depletion in mice increases testis weight and sperm reserve. In addition, we found that p43 deletion increases Sertoli cell proliferation in postnatal testis at 3 days of development. Electron microscopy studies evidence an alteration of mitochondrial morphology observed specifically in Sertoli cells of p43-/- mice. Moreover, gene expression studies indicate that the lack of p43 in testis induced an alteration of the mitochondrial-nuclear cross-talk. In particular, the up-regulation of Cdk4 and c-myc pathway in p43-/- probably explain the extended proliferation recorded in Sertoli cells of these mice. Our finding suggests that T3 limits post-natal Sertoli cell proliferation mainly through its mitochondrial T3 receptor p43.

An essential role for insulin and IGF1 receptors in regulating sertoli cell proliferation, testis size, and FSH action in mice.

Testis size and sperm production are directly correlated to the total number of adult Sertoli cells (SCs). Although the establishment of an adequate number of SCs is crucial for future male fertility, the identification and characterization of the factors regulating SC survival, proliferation, and maturation remain incomplete. To investigate whether the IGF system is required for germ cell (GC) and SC development and function, we inactivated the insulin receptor (Insr), the IGF1 receptor (Igf1r), or both receptors specifically in the GC lineage or in SCs. Whereas ablation of insulin/IGF signaling appears dispensable for GCs and spermatogenesis, adult testes of mice lacking both Insr and Igf1r in SCs (SC-Insr;Igf1r) displayed a 75% reduction in testis size and daily sperm production as a result of a reduced proliferation rate of immature SCs during the late fetal and early neonatal testicular period. In addition, in vivo analyses revealed that FSH requires the insulin/IGF signaling pathway to mediate its proliferative effects on immature SCs. Collectively, these results emphasize the essential role played by growth factors of the insulin family in regulating the final number of SCs, testis size, and daily sperm output. They also indicate that the insulin/IGF signaling pathway is required for FSH-mediated SC proliferation.

Thyroid hormone limits postnatal Sertoli cell proliferation in vivo by activation of its alpha1 isoform receptor (TRalpha1) present in these cells and by regulation of Cdk4/JunD/c-myc mRNA levels in mice.

Hypo- and hyperthyroidism alter testicular functions in the young. Among T3 receptors, TRalpha1 is ubiquitous, and its previously described knockout leads to an increase in testis weight and sperm production. We tested, for the first time, the hypothesis that TRalpha1-dependent regulation of Sertoli cell (SC) proliferation was directly regulated by TRalpha1 present in these cells. Thus, after crossing with the AMH-Cre line, we generated and analyzed a new line that expressed a dominant-negative TRalpha1 isoform (TRalpha(AMI)) in SCs only. So-called TRalpha(AMI)-SC (TRalpha(AMI/+) Cre(+)) mice exhibited similar phenotypic features to the knockout line: heavier testicular weight and higher sperm reserve, in comparison with their adequate controls (TRalpha(AMI/+) Cre(-)). SC density increased significantly as a result of a higher proliferative index at ages Postnatal Day (P) 0 and P3. When explants of control testes were cultured (at age P3), a significant decrease in the proliferation of SCs was observed in response to an excess of T3. This response was not observed in the TRalpha(AMI)-SC and knockout lines. Finally, when TRalpha(AMI) is present in SCs, the phenotype observed is similar to that of the knockout line. This study demonstrates that T3 limits postnatal SC proliferation by activation of TRalpha1 present in these cells. Moreover, quantitative RT-PCR provided evidence that regulation of the Cdk4/JunD/c-myc pathway was involved in this negative control.