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.
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.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques.
- natural sciencesbiological scienceszoologymammalogyprimatology
- natural sciencesbiological sciencesgeneticsgenomes
- natural sciencesbiological sciencesmolecular biologymolecular evolution
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Programme(s)
Topic(s)
Funding Scheme
ERC-STG - Starting GrantHost institution
75654 Paris
France