Knockdown of regulatory associated protein of TOR (raptor) in hypothalamus-stimulated folliculogenesis and induced ovarian cysts.

IF 1.8 4区生物学 Q3 DEVELOPMENTAL BIOLOGY

Reproduction, fertility, and development Pub Date : 2023-02-01 DOI:10.1071/RD21260

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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引用次数: 0

Abstract

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.

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下丘脑刺激的卵泡发生和诱导的卵巢囊肿中TOR(猛禽)调控相关蛋白的敲低。

背景:哺乳动物雷帕霉素靶蛋白复合物1 (mTORC1)是调节细胞生长、增殖和能量代谢等基本生物过程的重要传感器。用西罗莫司(一种mTORC1抑制剂)治疗疾病会引起不良反应，如女性生育障碍。目的:该研究的目的是破译下丘脑mTORC1下调的生殖后果。方法:在成年雌性小鼠(raptor小鼠)脑室内注射表达短发夹RNA (shRNA)对抗TOR (raptor)调控相关蛋白的慢病毒，诱导mTORC1表达降低。关键结果:与对照小鼠相比，猛禽小鼠具有生育能力，产仔数增加了15%。组织学分析显示窦腔、排卵前卵泡和卵巢囊肿增多。ShRaptor小鼠下丘脑GnRH mRNA和FSH水平显著升高。结论:这些结果支持了中枢神经系统mTORC1通过影响GnRH神经元活性参与调节女性生育能力和卵巢功能的假设。意义:这些结果表明，mTORC1活性的降低直接影响中枢神经系统，导致发情周期的失调，并诱导卵巢囊肿的发展。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Reproduction, fertility, and development 生物-动物学

CiteScore

2.10

自引率

10.50%

发文量

317

审稿时长

2 months

期刊介绍： Reproduction, Fertility and Development is an international journal for the publication of original and significant contributions on vertebrate reproductive and developmental biology. Subject areas include, but are not limited to: physiology, biochemistry, cell and molecular biology, endocrinology, genetics and epigenetics, behaviour, immunology and the development of reproductive technologies in humans, livestock and wildlife, and in pest management. Reproduction, Fertility and Development is a valuable resource for research scientists working in industry or academia on reproductive and developmental biology, clinicians and veterinarians interested in the basic science underlying their disciplines, and students. Reproduction, Fertility and Development is the official journal of the International Embryo Technology Society and the Society for Reproductive Biology. Reproduction, Fertility and Development is published with the endorsement of the Commonwealth Scientific and Industrial Research Organisation (CSIRO) and the Australian Academy of Science.