The cells of the ovarian surface epithelial (OSE) layer are the source of more than 90 percent of ovarian cancers. Pregnancy plays a crucial role in the prevention of ovarian cancer, but the mechanisms behind this role remain unclear. The present work aimed to examine the proliferative activity of the ovine OSE cells through the regular ovarian cycle and during pregnancy in ovine model and to investigate whether the underlying growing follicles have any influence on OSE layer. Adult ewe (Ovis aries) ovaries from cycling and pregnant animals were used. The ovaries were classified according to the reproductive status into: 1) ovaries from cycling ewes 2) ovaries from anoestrus ewes, and 3) ovaries from ewes with an identifiable pregnancy; the last group was further sub-divided into two sub-groups; ovaries in early-mid gestation and ovaries in mid-late gestation. Ovaries were removed immediately, fixed and stained with H&E. Quantification of ovarian follicles, PCNA and Ki-67 immunohistochemistry, and quantification of PCNA and Ki-67 immunostaining were performed. The present study revealed that there was no evidence of labelling for either marker PCNA or Ki-67 in the OSE from pregnant and anoestrus groups. Although the percentage of both markers was very low, 0.53 ± 0.05% for PCNA and 0.30 ±0.07% for Ki-67, the PCNA expression was significantly higher than the Ki-67. Analysis of OSE proliferating cells in cycling group revealed that the majority of PCNA and Ki-67-stained OSE cells were localised over the corpora lutea and a much lower fraction was found over the stroma. In addition, there was variation in the cellular morphology of the OSE cells that correlated to location. Nuclear staining for PCNA in granuolsa cells (GCs) of all types of follicles was higher than Ki-67 labelling, which was negligible in some of the follicular GCs. PCNA labelling was detected in oocytes of the primordial and transitory follicles development. Ki-67 was observed in GCs of follicles only from the primary stage and beyond with variation between groups. The expression of Ki-67 was statistically lower than PCNA in GCs of all types of follicles. The study revealed significant differences between the pattern of follicle distribution at different reproductive stages and follicles at primordial, transitory, primary, preantral, and antral stages in cycling, anoestrus, and pregnant ewe's stages. However, no significant difference was detected in the percentage of antral follicles between groups. In contrast, a significant increase was detected in the percentage antral follicles in the anoestrus group when compared to the cycling group. The results suggest that the protective role of pregnancy against epithelial ovarian cancer (EOC) could be influenced by the reduction in regulation of follicular activity caused by pregnancy factors that lead to a reduction in the levels of follicular products (hormones and growth factors). Thus the results suggest that during pregnancy and anoestrus the proliferative activity of the OSE cells is suppressed and the rate of follicular growth is reduced.
Key words: Mammalian Ovary, Ovarian Surface Epithelium, Epithelial Ovarian Cancers, Somatic Cells Follicle
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