Ovulatory Factor in Ovarian Carcinogenesis

Ovaries of mammals are covered by a simple layer of epithelial cells that originate from the coelomic mesothelium during embryonic development. The surface epithelium is supported over the ovarian cortical interstitium by a basement membrane, and is adjoined by desmosomes and gap or tight junctional complexes. Although the surface epithelium represents only a small fraction of the diverse cell types that populate the ovary, it is thought to account for approximately 90% of its malignancies (1).

Common cancer of the ovary is an ovulation-related disease. It has been known for decades that circumstances that avert ovulation, namely oral contraceptive use and pregnancy/lactation, protect against ovarian cancer (2–5). Until recently, it was unclear how the processes of ovulation and carcinogenesis might be linked.

A follicle selected to ovulate emerges from the ovarian cortex and comes into apposition with the surface epithelium. A complex interplay of proteolytic enzymes and inflammatory mediators liberated within the formative site of ovulation (i.e., at the follicular-ovarian surface interface) degrade collagen matrices and provoke cellular death. Surface epithelial cells within a limited diffusion radius become committed to apoptosis and are sloughed. In the finale, a physical force sustained by contractile elements within the basal wall of the follicle ruptures the devitalized fabric at the apex and expels the ovum (6).