Development of the polycystic ovarian condition (PCO) in the estradiol valerate-treated rat

A wide range of experimental manipulations results in an anovulatory polycystic ovarian (PCO) condition in the rat. Although PCO has been studied in a number of these models, research has centered on the condition after it is well established rather than as it develops. Consequently, it is still not clear exactly what follicular cysts are or how and why they form. Therefore, we studied the development of PCO in rats treated with estradiol-valerate (EV). In this model, definitive cysts were present 8-9 wk after a single injection of EV. Animals were killed at 5, 11, 16, 21, 28 and 56 days after EV treatment. Serum was assayed for luteinizing hormone (LH) and follicle-stimulating hormone (FSH). Ovaries were weighed and prepared for histologic examination. The ovaries were serially sectioned such that the number and size distribution of normal and atretic follicles could be assessed quantitatively. Oviducts were examined for the presence of ova. Immediately after EV treatment, ovulatory cycles ceased; by 16-20 days posttreatment, all animals exhibited persistent vaginal cornification. Basal concentrations of serum LH and FSH fell to a nadir at 11 days posttreatment, after which both gonadotropins exhibited a trend toward recovery. Within the first 28 days after treatment, ovarian weights declined significantly as did the total number of healthy follicles. Atretic follicles of all sizes were particularly numerous at 16 days. By 28 days, the decline in the number of healthy follicles reached a plateau. Numerous atretic, large secondary follicles were particularly prominent on the background of the decreasing number of normal follicles.