Endocrine and morphological features of cystic ovarian condition in antiprogesterone RU486-treated rats

Abstract

Four-day cyclic Wistar rats (200 g body wt) were injected (sc) with the antiprogestagen RU486 (4 mg RU486/0.2 ml oil) on estrus, metestrus, diestrus and proestrus. Groups of rats (12–15) were decapitated on days 1 (day of expected ovulation), 5, 9, 13, 17 and 21 after the 4 days of RU486 treatment. Oil-injected rats decapitated on proestrus (day 0) and estrus (day 1 ) served as controls. In both controls and RU486-treated rats, the following parameters were noted: ovulation, vaginal smears and luteinizing hormone (LH), follicle-stimulating hormone (FSH), prolactin, testosterone and estradiol-1 7β serum concentrations. Also, pituitary, adrenal, uterus and ovary weight were recorded. RU486 induced ovulation blockade, persistent vaginal cornification, uterine ballooning and increased serum levels of LH, FSH, prolactin, testosterone and estradiol. Furthermore, the LH/FSH and testosterone/estradiol ratios in serum increased. Pituitary and ovary weights also increased. The enlarged ovaries showed follicular cysts undergoing atresia and/or different degrees of luteinization of granulosa cells resembling, in some cases, genuine corpus luteum containing the ovocyte. The small follicles showed extensive atresia and stimulated thecal cells. These effects are reversible and remain in a stationary state for about 9–13 days after RU486 treatment. While the endocrinological alterations found in rats treated with RU486 are similar to those exhibited in polycystic ovarian disease, the morphological alterations found in the ovaries seem to be more closely related to the multicystic ovarian condition. Overall, the results suggest that progesterone deficiency may be of relevance in the initiation of the cystic condition in the rat, and support the concept that a lack of progesterone is conducive to the perpetuation of the cystic state after the cyst follicles first develop.