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The evolution of menstruation in primates

Project description

Decoding the genetics of menstruation evolution in primates

The shedding of the superficial endometrium (menstruation) is a recent evolutionary attribute. It occurs only in few placental mammals (including humans and baboons), when in most other mammalian species the endometrium is reabsorbed at the end of the cycle. Scientists can’t explain this mechanism, but it is crucial for understanding gynaecological disorders. The EU-funded EVOMENS project will identify the gene networks and non-coding regulatory elements that control the advent of menstruation in primates. It will apply single-cell transcriptomics and deep transcriptomics to reconstruct the cellular developmental transition occurring in the uterus, model transcriptional dynamics and compare (at the cellular, functional and genetic levels) five primate species. EVOMENS will explain the evolutionary dynamics of the adoption of menstruation making the physiology of human reproduction more legible.

Objective

Menstruation is a recent evolutionary innovation in primates: the trait is present in some species (humans, baboons) but not in closely related others (orangutans, vervets). In the latter and in most mammals, the uterine endometrium is reabsorbed at the end of the cycle instead of being shed when fecundation has not occurred. The molecular and genetic underpinnings of this complex process are not fully understood, despite its critical involvement in gynaecological conditions. I propose to discover the molecular mechanisms leading to menstruation by comparing the uterine linings from five primate species at the cellular, functional and genetic levels. The objectives are to identify the gene networks and non-coding regulatory elements that control the advent of menstruation in primates, and to understand how this genetically inherited trait was acquired in primate genomes during the evolution of the human lineage.
In Aim 1, I will leverage single-cell transcriptomics to uncover the cellular composition and marker modifications that differentiate the uterine linings of menstruating and non-menstruating primates.
In Aim 2, I will use deep transcriptomics and accessible chromatin assays on sorted endometrial cell populations to identify genes and non-coding regulatory regions differentially activated in menstruating species. This analysis will reveal the molecular pathways, regulation networks and cellular interplay involved in uterine tissue shedding vs. reabsorption.
In Aim 3, I will replace these modifications within the context of primate genome evolution: I will elucidate the mutational dynamics by which genetic novelty has emerged during the adoption of menstruation, and how the functional divergence of the endometrium compares to other reproductive and somatic tissues.
This project will enhance our understanding of a key physiological trait for human reproduction as well as a dramatic example of functional innovation in the primate lineage.

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Programme(s)

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Topic(s)

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Funding Scheme

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ERC-STG - Starting Grant

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Call for proposal

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(opens in new window) ERC-2019-STG

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Host institution

INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE
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.

€ 1 185 250,00
Total cost

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€ 1 185 250,00

Beneficiaries (1)

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