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WJ Murdoch and AC McDonnel

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 urokinase-type plasminogen activator in response to surge concentrations of (locally delivered) gonadotrophins. Urokinase activates latent collagenases and stimulates release of tumour necrosis factor alpha from thecal endothelium. Tumour necrosis factor alpha progressively induces matrix metalloproteinase gene expression, apoptosis and inflammatory necrosis. Collagenolysis and cellular death are a prelude to stigma formation and ovarian rupture. Epithelium exfoliated from the dome of ovulatory follicles is replenished by generative stem cell replication and migration from the wound edges. Common epithelial ovarian cancer has been related to successive bouts of ovulation and mitosis. The integrity of the DNA of surface cells circumjacent to the ovarian rupture site is compromised during the ovulatory process. Clonal expansion of an epithelial cell with damaged (unrepaired) DNA is a putative factor in carcinogenesis. Ovarian cancer is a deadly insidious disease because typically it is asymptomatic until the malignancy has reached beyond the ovaries.

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AC McDonnel, EA Van Kirk, KJ Austin, TR Hansen, EL Belden and WJ Murdoch

Cancer antigen 125 (CA-125) is expressed by malignant human ovarian surface epithelial cells and derivatives of the Mullerian duct system. This study explored the expression, regulation, and function of CA-125 in the bovine uterus. CA-125 was localized by immunohistochemistry to the apical surfaces of epithelial cells lining the endometrium and proximal glands of the late luteal phase and early pregnancy; antigen was not detected during oestrus or the postpartum period. Production of CA-125 by bovine endometrial cells in vitro was upregulated by progesterone and interferon-tau. Immunopurified CA-125 from uterine flushes of dioestrous or pregnant cows was similar in biochemical composition (as determined by gel electrophoresis and amino acid content) to the human antigen isolated from incubation medium conditioned by the ovarian cancer cell line OVCAR-3. Bovine CA-125 inhibited complement-induced lysis of antibody-sensitized sheep erythrocytes. It is suggested that endometrial CA-125 exerts a progestational role in part by protecting maternal and embryonic cells from immune targeting and lysis.