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Role of the neuroendocrine axis and its link with obesity in the genesis of PCOS

Objective

Polycystic ovary syndrome (PCOS) is a human hormonal disorder of complex etiology, characterized by reproductive, endocrine and metabolic abnormalities, which affects 15% of women of reproductive age and has a very low survival rate. Recent studies on its pathophysiology suggest that it reflects alterations in homeostatic feedback mechanisms between the ovaries, adipose tissue, and hypothalamic circuits that develop during embryogenesis. Despite its high prevalence and significant impact on health, there are no effective treatments for PCOS due to its complex etiology.
The development of new animal models displaying features of human PCOS is an unmet need because classical mouse models of PCOS have relied on its induction with androgen excess, providing only very limited insight into the pathogenesis of PCOS.
In a genetic screen against secretable and transmembrane proteins involved in tissue-to-tissue communication, the host lab has identified new genes that act as sensors of the amount of body fat in the larval prothoracic endocrine gland of Drosophila. This gland corresponds to the neurosecretory part of the mammalian hypothalamus and mutants in these genes are characterized by PCOS.
The main objective of this proposal is to characterize how cell communication in the neuroendocrine-adipose tissue-ovary axis is responsible for the uncontrolled proliferation of gonadal germ cells. The underlying PCOS will be studied using single-cell genomic approaches, metabolomics, and genetic studies on the different elements that make up this axis. By elucidating the molecular/hormonal mechanisms involved in brain-adipose tissue-ovary communication in normal development and disease, I hope to better define the pathogenesis and development of targeted therapies against PCOS.

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Topic(s)

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HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships

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Call for proposal

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(opens in new window) HORIZON-MSCA-2022-PF-01

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Coordinator

AGENCIA ESTATAL CONSEJO SUPERIOR DE INVESTIGACIONES CIENTIFICAS
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 181 152,96
Address
CALLE SERRANO 117
28006 MADRID
Spain

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Region
Comunidad de Madrid Comunidad de Madrid Madrid
Activity type
Research Organisations
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Total cost

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