566
EFFECTS OF BISDEHYDRODOISYNOLIC ACIDS ON THE REPRODUCTIVE HISTOLOGY OF FEMALE RATS.
Ellis, Stefanie1, Perseli, Dora1, Roeder, Mikelle1, Hou, Yuqing3,4, Adler, Stuart2, Meyers, Cal3,4, Banz, William1,2, Winters, Todd1,2, 1 3 4 2
ABSTRACT- Bisdehydrodoisynolic acids (BDDA), D-ring seco-steroids formed from the alkaline fusion of the equine estrogen, equilenin, elicit varying physiological estrogenic responses. Our objective was to determine ovarian and uterine responses to the separate enantiomers or a racemic mixture of the BDDA compounds compared with estradiol and vehicle in mature intact female rats. In two experiments, rats received a daily subcutaneous injection [3.8 (Exp. 1, 5 wk) or 4.6 (Exp. 2, 7 wk) g/g BW in 0.1 mL of a 10% ethanol:90% olive oil vehicle] of the respective compounds. Reproductive organs were obtained and sectioned for histological examination. Ovarian primary, secondary, tertiary, and atretic follicles and corpora lutea were counted in Exp. 1. Area, width, and length of mucosal cells (MC) of the uterine endometrial lining were measured for both experiments. In Exp. 1, (±)- and (+)-BDDA decreased (P < 0.05) numbers of all follicle types except atretic, suggesting systemic feedback effects on the hypothalamic-pituitary-ovarian axis. Corpora lutea were unaffected (P > 0.10). The uterine weight/BW ratios were increased (P = 0.044) by the BDDA compounds. The (±)-BDDA increased area (P = 0.002), width (P = 0.001), and length (P = 0.006) of the MC. Introduced in Exp. 2, (-)-BDDA decreased uterine weight/BW ratio by 66% (P = 0.014) compared with all treatments except the vehicle, and reduced MC area (P = 0.0008) and width (P < 0.0001) compared with all other treatments. The BDDA compounds elicit varying estrogenic responses, with specific enantiomers possibly displaying selective estrogen receptor modulator (SERM) activity.
KEY WORDS: Bisdehydrodoisynolic Acid, Ovary, Uterus, Rat