Knockdown of regulatory associated protein of TOR (raptor) in hypothalamus-stimulated folliculogenesis and induced ovarian cysts
| Autor: | Pauline Tartarin, Matthieu Keller, Edith Guibert, Elliott Trives, Guillaume Bourdon, Pablo Chamero, Didier Negre, Fabien Cornilleau, Vanaique Guillory, Eric JeanPierre, Caroline Costa, Stéphanie Migrenne, Joelle Dupont, Pascal Froment |
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| Přispěvatelé: | Physiologie de la reproduction et des comportements [Nouzilly] (PRC), Institut Français du Cheval et de l'Equitation [Saumur] (IFCE)-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), École normale supérieure de Lyon (ENS de Lyon), Infectiologie et Santé Publique (UMR ISP), Université de Tours (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Unité de Biologie Fonctionnelle et Adaptative (BFA (UMR_8251 / U1133)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité) |
| Rok vydání: | 2022 |
| Předmět: | |
| Zdroj: | Reproduction, Fertility and Development Reproduction, Fertility and Development, 2023, 35 (4), pp.307-320. ⟨10.1071/RD21260⟩ |
| ISSN: | 1031-3613 |
| DOI: | 10.1071/RD21260⟩ |
| Popis: | Context Mammalian target of rapamycin complex 1 (mTORC1) is an essential sensor that regulates fundamental biological processes like cell growth, proliferation and energy metabolism. The treatment of disease by sirolimus, a mTORC1 inhibitor, causes adverse effects, such as female fertility disorders. Aims The objective of the study was to decipher the reproductive consequences of a downregulation of mTORC1 in the hypothalamus. Methods The reduced expression of mTORC1 was induced after intracerebroventricular injection of lentivirus expressing a short hairpin RNA (shRNA) against regulatory associated protein of TOR (raptor) in adult female mice (ShRaptor mice). Key results The ShRaptor mice were fertile and exhibited a 15% increase in the litter size compared with control mice. The histological analysis showed an increase in antral, preovulatory follicles and ovarian cysts. In the hypothalamus, the GnRH mRNA and FSH levels in ShRaptor mice were significantly elevated. Conclusions These results support the hypothesis that mTORC1 in the central nervous system participates in the regulation of female fertility and ovarian function by influencing the GnRH neuronal activity. Implications These results suggest that a lower mTORC1 activity directly the central nervous system leads to a deregulation in the oestrous cycle and an induction of ovarian cyst development. |
| Databáze: | OpenAIRE |
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