Camille Berthelot

The mammalian uterus is a key reproductive organ composed of a dynamic, hormone-responsive mucosa encapsulated in a smooth muscle, which serves as a matrix for embryo implantation and contributes to placenta development. Despite its importance for reproduction, the uterus remains poorly characterized at the cellular and molecular levels. We strive to understand the genetic mechanisms of its phenotypic variations through comparisons of functional genomics data across species, and between health and disease states. 

Evolution of uterine traits in mammals. Uterine functions evolve quickly and can display profound differences between related species. A striking example is menstruation, or the sloughing of the uterine mucosa at the end of each hormonal cycle, which evolved at least four times independently in mammals. Similarly, the mechanisms of embryo implantation and placenta establishment vary between species, with rapid switches between phenotypes. To illuminate the genetic and molecular tenets of these phenotypic changes, we characterize how uterine hormonal responses and embryo attachment pathways have changed between mammals at the transcriptomic and regulatory levels.

Evolution of uterine traits in humans. Many uterine traits are variable in human populations (menstrual flow abundance, prevalence of uterine diseases), and some of these variations are caused by genetic differences between individuals. The nature and mechanisms of action of these genetic variants are not well understood, as genes and pathways at play in the uterus are poorly annotated. However, genetic variations affecting reproductive functions can result in disease and impact fertility: therefore, they should in theory be directly accessible to natural selection. We aim to identify such signatures of recent selection in the human genome linked to variations in uterine functions, which would represent markers of functional importance and shed light on the genetic architecture of complex traits.

Alterations of uterine functions in endometriosis. Endometriosis is a common gynecological disease affecting 6-10% of women in their reproductive years, and the leading cause of female infertility. It is defined by the growth of functional uterine mucosal tissue (endometrium) outside the uterine cavity. Endometriosis occurs by dissemination of endometrial cells from the uterus into the peritoneal cavity during menstruation, known as retrograde menstruation. However, retrograde menstruation occurs in most women without consequences, suggesting that endometrial cells contained in menstrual fluid of endometriosis patients present functional alterations that favor reimplantation and proliferation. We investigate how menstrual fluid composition differs in endometriosis patients, and whether menstrual fluid is an overlooked potential tool for endometriosis diagnosis.