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Influence de l'acide rétinoïque et des stéroïdes sexuels sur l'entrée en méiose des cellules germinales et la prolifération des cellules de tumeurs testiculaires d'origine germinale

Abstract : Retinoic acid (RA) is involved in germ cells meiosis onset (CGs) in amniotes (Bowles et al., 2006 ; Smith et al., 2008). The aim of the first part of our study was to determine if RA is able to induce meiosis entry in the urodele amphibian Pleurodeles waltl. Our data on PwDmc1 (meiosis marker) expression indicate an earlier meiosis onset in females compared with males depending on RA biosynthesis. In vitro, the treatment of male and female gonads with RA induces an earlier meiosis entry in both sexes. Moreover, we have shown that RA biosynthesis is regulated by steroid hormones. Therefore, the mechanisms which trigger GCs differentiation in mammals might be conserved in urodeles. Many studies indicated that in utero xenobiotic exposure is able to induce alterations in GCs differentiation. These neoplasic cells enter in a period of dormancy until after puberty where they proliferate and the testicular tumours emerge. This prepubertal dormancy suggests that the testicular cancer development is hormone sensitive (McIntyre et al., 2008). In the second part we studied the effects of steroid hormones on the proliferation of the seminoma cell line TCam2. Our results indicate that estradiol and testosterone can induce the proliferation of this cell line and the expression of ER[alpha]36, a truncated form of estrogen receptor alpha. This expression is stimulated by GPER-cAMP/PKA signalisation pathway and activates EGFR expression. ER[alpha]36 could be a potential therapeutic target.
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https://hal.univ-lorraine.fr/tel-01746220
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Angelina Wallacides. Influence de l'acide rétinoïque et des stéroïdes sexuels sur l'entrée en méiose des cellules germinales et la prolifération des cellules de tumeurs testiculaires d'origine germinale. Médecine humaine et pathologie. Université Henri Poincaré - Nancy 1, 2011. Français. ⟨NNT : 2011NAN10057⟩. ⟨tel-01746220⟩

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