Ovulation: A cellular symphony in three movements

Abstract

Ovulation is a complex and tightly regulated process essential for mammalian reproduction. It involves the coordinated, tissue-scale remodelling of the ovulatory follicle, culminating in the release of a fertilisation-competent egg. Ovulation is triggered by external hormonal cues: rising levels of follicle-stimulating hormone (FSH), followed by a surge in luteinising hormone (LH) from the anterior pituitary. These cues initiate a cascade of downstream events driven by follicle-derived signals, including epidermal growth factor (EGF) and progesterone, which propagate the ovulatory response. Recent advances using ex vivo follicle culture and live imaging in mouse follicles have revealed ovulation as a stepwise, self-contained programme characterised by dynamic spatial and temporal coordination. Notably, the oocyte remains largely stationary during most of ovulation, only moving toward the rupture site minutes before its release. This finding emphasises that ovulation is not defined by egg release alone, but by a prolonged and tightly regulated sequence of cellular and tissue-level events. This review presents ovulation through a temporal framework, metaphorically structured as a symphony performed by the four major follicular cell types. Beginning with an FSH-driven prelude, the symphony progresses through three movements: LH-induced initiation and meiotic resumption; progesterone-driven late events; and finally, follicle rupture and oocyte release. Together, this framework offers a new lens to understand ovulation as a developmental performance marking the transition from reproductive readiness to potential fertilisation and new life.