OvSpring

Wider research context / theoretical framework The origin of new life is one of the most fundamental questions in biology. During ovulation, the maternal contribution—the egg—is released from an ovarian follicle. Ovulation is a highly dynamic process that occurs within the body, making it challenging to directly study both the event and its underlying mechanisms. During ovulation, the follicle undergoes dramatic morphological changes, ultimately leading to tissue rupture and egg release. Despite their importance, the role of mechanical forces in ovulation is unknown, representing a significant gap in our understanding of the process and its related causes of infertility. Recently, the THOMAS lab developed a novel model system to study ovulation using live microscopy in isolated mouse follicles that enables the study of the dynamics of ovulation in a systematic and quantitative manner. The RUPRECHT lab has shown that cell shape changes activate mechano-transduction mechanisms in the nucleus, regulating cell mechanics via cPLA2 activation. Importantly, cPLA2 is also a mediator of prostaglandin production in the follicle, suggesting a close crosstalk between cell shape, mechanics, and hormone signaling during ovulation. Hypotheses / research questions / objectives We hypothesize that mechanical stretching of somatic cells surrounding the oocyte activates mechano-transduction pathways that play a key role in ovulation by establishing a mechano-signaling crosstalk between cell types within the follicle. Our research objectives will address 1) structural changes in cell and nucleus architecture, 2) mapping mechanical changes in the follicle, 3) identifying key mechano-signaling pathways and 4) studying their functional role in ovulation. Approach / Methods In this project, we will establish a cross-disciplinary and quantitative approach to investigate how mechanical forces during ovulation are generated and sensed to ensure robust egg release. Our study will use advanced live cell imaging of isolated follicles in combination with transcriptomics, quantitative biophysical tools and targeted molecular perturbations. By using both zebrafish and mouse ovaries as model systems, we will comparatively assess the mechanical regulation of ovulation across species. Level of originality / innovation OvSpring will provide fundamental new insights into the role of mechanical forces in ovulation—an essential yet poorly understood process in female fertility. This interdisciplinary project will be the first to systematically compare mechano-regulatory processes in ovulation across vertebrate species. Combining the complementary expertise of both coordinators will address conserved mechanical principles in reproductive biology, opening new avenues for understanding fertility and ovarian dysfunction. Primary researchers involved Dr. Christopher THOMAS, IBDM Marseille, France Univ.Prof. Dr. Verena RUPRECHT, University Innsbruck, Austria