Summary
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.
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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| Web resources: | https://cordis.europa.eu/project/id/101109123 |
| Start date: | 01-05-2023 |
| End date: | 30-04-2025 |
| Total budget - Public funding: | - 181 152,00 Euro |
Cordis data
Original description
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.
Status
SIGNEDCall topic
HORIZON-MSCA-2022-PF-01-01Update Date
31-07-2023
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