Project description
A better understanding of ovulation to improve female fertility
Ovulatory dysfunction is a common cause of women's infertility, often associated with conditions such as polycystic ovary syndrome, hypothalamic amenorrhea or premature ovarian insufficiency. Hypothalamic gonadotropin-releasing hormone-expressing (GnRH) neurons control the release of reproductive hormones from the pituitary gland. It has been suggested that upstream Kiss1 neurons are crucial for the activation of GnRH neurons and the preovulatory surge of gonadotropins leading to ovulation. Substance P, a member of the neuron tachykinin neuropeptide family, has been shown to regulate gonadotropin release and might modulate the preovulatory surge in mice. The EU-funded Tac1-Ovulation project will apply functional genomics to assess the role of substance P signalling in Kiss1 and GnRH neurons in the process of ovulation.
Objective
Reproductive health is deteriorating worldwide, via as yet unknown mechanisms. The most common cause of in/subfertility in women is ovulatory dysfunction; anovulation being associated to conditions as polycystic ovary syndrome, hypothalamic amenorrhea and premature ovarian insufficiency. Hence, better understanding of the mechanisms controlling ovulation is mandatory for improved management of reproductive disorders.
While hypothalamic GnRH neurons are the major output pathway for the brain control of ovulation, upstream Kiss1 neurons, particularly in the rostral hypothalamic area in rodents, have been suggested to be crucial for the timed activation of GnRH neurons and generation of the preovulatory surge of gonadotropins that drives ovulation. However, the major regulators of this Kiss1/GnRH pathway remains ill defined. Substance P (SP, encoded by Tac1), a member of the tachykinin (TAC) family that acts via the receptor, NK1R (encoded by Tacr1), has been shown to centrally regulate gonadotropin release, and, according to our preliminary data, might modulate the pre-ovulatory surge in mice. Yet, the patho-physiological relevance of SP/NK1R signaling in ovulatory control needs to be defined.
Here, we will apply functional genomics and virogenetic approaches to assess the roles and mechanisms of action of SP/NK1R signaling in the control of ovulation, with special attention to its actions in Kiss1 and GnRH neurons. To this end, we will apply (i) virogenetic-driven Tacr1 silencing in Kiss1 and GnRH neurons; (ii) tracing techniques to map Tac1 neuronal projections to Kiss1 and GnRH neurons; and (ii) chemo-genetic manipulation of Tac1 neurons, via excitatory and inhibitory DREADDs, coupled to monitoring of gonadotropin secretion and ovulation. Our project, which is based on our solid preliminary data, will expand our understanding of the mechanisms controlling ovulation and female fertility, helping to define novel strategies for reproductive control in the future.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- medical and health sciences health sciences social medicine sexual health
- medical and health sciences clinical medicine clinical neurology
- natural sciences biological sciences reproductive biology
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Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions
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H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility
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Topic(s)
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Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Funding Scheme
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Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
MSCA-IF-EF-RI - RI – Reintegration panel
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Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) H2020-MSCA-IF-2019
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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.
14005 CORDOBA
Spain
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