on on structure of mitochondria in Sertoli and germ cells we performed electron microscopy. In p432/2 mice the shape of mitochondria is only modified in SC. They are more expanded showing a lower electron density compared with control mice. On the other hand, mitochondria observed in p432/2 germ cells shown the same histological picture than in controls. This result indicates that p43 deletion induced a deep modification of mitochondrial morphology in SC. Mitochondrial Gene Expression is Altered in p432/2 Testes at P3 As previously done for cell cycle actors, we analysed by Q-PCR 84 candidate genes putatively involved in the mitochondrial function which could explain the increase in SC proliferation observed in p432/2 mice at P3,. These genes are involved in: small transport of molecules, in import and cleavage of proteins, in metabolism, in localization of proteins mitochondrial localization, in apoptosis and in cell cycle. No down-regulated genes were found. These results demonstrate that the mitochondrial T3 receptor plays an important role in many mitochondria functions. Discussion We show for the first time a mitochondrial control of the differentiation of Sertoli cells by T3 via the mitochondrial T3 receptor p43. p432/2 mice display a testicular phenotype which is very similar to the phenotype of TRa0/0 knockout mice, with an increase in testicular sperm reserve 9435190 and testis weight. In vivo at P3, the SC proliferation index was significantly higher in both p432/2 and TRa0/0 mice than in their respective controls. Recently, it was demonstrated that the dominant-negative TRa1L400R5 only expressed in Sertoli cells displays a testis phenotype, which is very similar to the phenotype of TRa0/0 and p432/2 mice. These interesting results 7 p43 Receptor Controls Sertoli Cell Proliferation evidenced that an increase in round spermatid number was the consequence of an increase in the proliferation rate of Sertoli cells during postnatal period. The similar phenotype observed in p432/2, TRa0/0 and TRaAMISC testis prompt us to propose that the mitochondrial p43 receptor could be the main T3 receptor isoform involved in the physiological situation of T3control of the post-natal Sertoli cell development. The prolifera- tion rate of Sertoli cells during post natal period is mainly regulated by FSH. But recently Pitetti et al. show that ablation of insulin/IGF signalling 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 periods. These analyses revealed that the insulin/IGF signalling pathway is required for FSH-mediated SC proliferation. Here we found that the plasma FSH level was the same in p432/2 mice than in WT mice at 5 months of age. However, we have previously showed that the depletion of p43 induces a loss of glucosestimulated insulin secretion. Insulin levels were significantly higher in p432/2 mice in fasting condition and lower after refeeding. Perhaps, these defects in insulin Triptolide secretion in p432/2 mice could activate insulin/IGF pathway and potentiate the action of FSH on Sertoli cells. This result demonstrates and confirms that the mitochondrial p43 receptor has physiological functions. In fact, recently, this receptor has been shown to be involved in the control of the secretion of insulin from the pancreas and glucose 14707029 homeostasis and to affect muscle mass and the metabolic and contractile features of myofibers in mice. The physiologic

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