Revealing the Secrets of Ovulation

Ovulation is essential for reproduction. During ovulation, an egg is released from an ovarian follicle into the oviduct. Once released, the egg can be fertilised by the sperm and give rise to a new embryo. Ovulation takes place inside the body, impeding studies of its progression. The exact mechanisms that control ovulation have therefore remained unclear. In this work, we devised methods to study the entire process of ovulation live in isolated ovarian follicles from mice using a long-term culture and imaging system. A combined approach of confocal and two-photon microscopy allowed for the study of ovarian processes at both the cellular and whole follicle scale. We show that ovulation proceeds through three distinct phases, follicle expansion (I), contraction (II), and rupture (III), culminating in the release of the egg. Follicle expansion is driven by the secretion of hyaluronic acid, and an osmotic gradient-directed influx of fluid into the follicle. Subsequently, smooth muscle cells in the outer follicle drive follicle contraction. Follicle rupture is initiated by the formation of a stigma in the thinnest region of the follicle wall, followed by the exit of follicular fluid and cumulus cells, and finally, the rapid release of the egg. Taken together, these results establish a mechanistic framework for ovulation, a process of fundamental importance to reproduction