Oxidative base (8-oxoguanine) damage, DNA fragmentation, and apoptosis occurred among ovarian surface epithelial cells within the formative site of ovulation in sheep. The incidence of 8-oxoguanine adducts in surviving antiapoptotic Bcl-2/base excision repair polymerase beta-positive cells at the margins of ruptured follicles (which avoid the focal point of the ovulatory assault) was intermediate between apoptotic and outlying healthy epithelium. Cells containing perturbations to DNA expressed the tumor suppressor p53. Localized reactions of DNA injury and programmed cellular death were averted by ovulation blockade with indomethacin. Progesterone enhanced the biosynthesis of polymerase beta in ovarian surface epithelial cells exposed in vitro to a sublethal concentration of H(2)O(2). Ovulation is a putative etiological factor in common epithelial ovarian cancer. A genetically altered progenitor cell, with unrepaired DNA, but not committed to death, could give rise to a transformed phenotype that is hence propagated upon healing of the ovulatory wound; it appears that this incongruity is normally reconciled by up-regulation of the base excision repair pathway during the ensuing luteal phase.

The mammalian ovary is covered by a singular layer of epithelial cells. The rather unassuming character of the ovarian surface epithelium has generally inclined reproductive physiologists to question its functional significance. However, recent experimental evidence indicates that the ovarian epithelium is an obligate component of the ovulatory process. That most ovarian cancers arise by transformation of a surface epithelial cell affected by ovulation has been a point of theory for three decades. The objectives of this overview are to consider the morphology and developmental biology of the ovarian surface epithelium and to delineate its apparent roles in ovulation and pathogenesis. Anatomy and embryonic origin of the ovarian surface epitheliumOvarian surface epithelial cells vary in type from simple squamous to cuboidal to low pseudostratified columnar. The surface epithelium is supported over the ovarian cortical interstitium (tunica albuginea) by a basement membrane ( Fig. 1) and is held together laterally by desmosomes and gap or tight junctional complexes. Surface cells are continuous at the hilum with the mesothelium of the ovarian ligament (mesovarium) and peritoneum. Preferential outgrowth of a preovulatory follicle brings it into close apposition with the ovarian surface. In most mammals, the entire surface of the ovary, other than those regions disrupted by ovulation, is covered by epithelial cells. However, in equids, the ovarian epithelium (and ovulation) is restricted to a discrete area of depression known as the fossa, and the remainder of the ovary is encased by serosa-containing elastic bands of connective tissue (Walt et al., 1979). Ovarian surface epithelial cells have a mesodermal derivation shared with the epithelia of the urogenital system and adrenal cortex. Mesoderm segregates during embryonic development into pluripotent mesenchyme and coelomic epithelium (peritoneal mesothelium). Mullerian mesothelium is the precursor of oviductal, endometrial, and cervical epithelia. Ovarian surface epithelium differentiates after invagination of the coelomic mesothelium over the gonadal ridges (Byskov, 1986). In species with an ovulation fossa, the cortex (with modified epithelium) migrates into the medullary portion of the ovary during the postnatal period (Walt et al., 1979). Early investigators assumed that ova were derived from the ovarian surface; hence, the misnomer 'germinal' epithelium. Role of the ovarian surface epithelium in the mechanism of ovulatory follicular ruptureThe contention that ovarian surface epithelial cells participate actively in the biomechanics of gonadotrophin-induced Although ovarian mechanisms of ovulation have been a subject of investigation for more than a century, essential regulatory pathways remain uncertain. A role for the ovarian surface epithelium in ovulation has recently been demonstrated. Ovarian surface epithelial cells in close contact with the apical wall of preovulatory ovine follicles secrete a urokinasetype plasminogen activator in response to surge conc...

The lethality of common (surface) epithelial ovarian cancer is contingent on its metastatic capacity. Dissemination of the neoplasia throughout the abdominal cavity has been associated with secretion of proteolytic enzymes from vesicles shed by ovarian cancer cells. We report that the lipophilic steroid hormone progesterone decreases the fluid dynamics of plasma membranes of human SKOV-3 adenocarcinoma cells. The decrease in membrane fluidity was related to an inhibition in vitro of exocytotic vesicle release, cellular invasiveness into Matrigel, and colony formation in three-dimensional collagen matrix. Tumorigenesis was suppressed by progesterone in immunocompromised nude mice inoculated intraperitoneally with SKOV-3 cells. Progestins could therefore be of benefit in the prevention and(or) treatment of early-stage ovarian carcinomatosis.

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