1. Unveiling the reciprocal dialogue between oocytes and cumulus oophorus cells that surround them

A key function of the ovary is to generate, through folliculogenesis, fertilizable oocytes capable of supporting subsequent preimplantation embryonic development. Follicle growth is regulated by a finely coordinated bidirectional communication between the oocyte and the surrounding granulosa and cumulus cells (GC and CC) through paracrine exchange of nutrients and signaling molecules. Recently, we have developed a co-culture platform between oocytes and CCs, demonstrating that only specific CCs can contribute to oocyte developmental competence and release extracellular vesicles containing microRNAs known for their association with genes regulating follicle maturation and oocyte developmental competence.

2. Building a functional 4D digital model of the ovary and testicle

Organs are hierarchically organized into integrative levels of spatial-functional organisation. Their activity is based on key functional units, their shape, spatial localisation, and reciprocal relationships, as well as their specific physiology and molecular landscape. To understand the underlying complexity of these relationships, how an organ functions, and how it deviates from homeostasis to dysfunction, we must learn to represent the spatial association and temporal dynamics among its functional components within the three-dimensional (3D) architecture of the organ.

At LBBR we employ an interdisciplinary approach based on tomographic and optical imaging, correlative microscopy, histochemistry, and molecular biology (including spatial transcriptomics). Collaborating with engineering colleagues and leveraging machine and deep learning, we construct a digital model of gonads that aims not only at describing, but also predicting, the architectural and temporal changes (4D, space + time). This computational tool will allow us, for example, to study the continuously changing relationship between follicles and their vascularization in the ovary. It will describe both territorial and functional dynamics occurring from birth to adulthood, during aging, and in response to pathological changes.