Mobini Far Hamid Reza, Agren Greta, Lindqvist Ann-Sophie, Marmendal Maarit, Fahlke Claudia, Thiblin Ingemar
Department of Surgical Science, Division of Forensic Medicine, Uppsala University, Dag Hammarskjölds väg 17, S-752 37 Uppsala, Sweden.
Eur J Obstet Gynecol Reprod Biol. 2007 Apr;131(2):189-97. doi: 10.1016/j.ejogrb.2006.07.037. Epub 2006 Sep 18.
The aim of the present investigation was to characterize the effects of supraphysiological doses of the anabolic androgenic steroid nandrolone decanoate (ND) on the fertility of female rats, as well as on the morphology of their uterus.
Female Wistar rats (n=15) received a subcutaneous injection of ND (15 mg/kg) once daily during a 2-week period, while the control animals (n=10) were administered vehicle alone (arachidis oleum) in the same manner. Estrus behavior was evaluated 4 weeks after termination of this treatment and in cases where signs of receptivity were present, the female rat was given the opportunity to copulate with a male. After breeding, the female animals were sacrificed and their uteri examined histomorphologically.
All ND-treated animals exhibited abnormal vaginal smears, whereas all of the control smears were normal. Most (73%) of the treated females demonstrated normal estrus behavior (i.e., willingness) on the day of mating, but none got pregnant; whereas all of the control rats became pregnant. The female rats receiving the ND showed an enhanced rate of weight gain and the myometrium thickness of their uteri was significantly increased, while the endometrium was significantly thinner. Furthermore, ND caused a significant proportion of the treated animals to display tortuous and irregularly branching endometrial glands, as well as a lack of the physiologically normal infiltration of eosinophilic leukocytes into the endometrium (endometrial eosinophilic homing), a finding that has not been reported previously.
The present findings indicate that high doses of ND cause morphological and physiological alterations in the uterus of female rats that are associated with a suppression of their reproductive capacity.
本研究旨在表征超生理剂量的合成代谢雄激素类固醇癸酸诺龙(ND)对雌性大鼠生育能力及其子宫形态的影响。
雌性Wistar大鼠(n = 15)在2周内每天皮下注射一次ND(15 mg/kg),而对照动物(n = 10)以相同方式仅给予赋形剂(花生油)。在该治疗结束后4周评估发情行为,在出现接受迹象的情况下,给予雌性大鼠与雄性交配的机会。交配后,处死雌性动物并对其子宫进行组织形态学检查。
所有接受ND治疗的动物阴道涂片均异常,而所有对照涂片均正常。大多数(73%)接受治疗的雌性在交配当天表现出正常的发情行为(即意愿),但均未怀孕;而所有对照大鼠均怀孕。接受ND的雌性大鼠体重增加率提高,子宫肌层厚度显著增加,而子宫内膜显著变薄。此外,ND导致相当比例的治疗动物出现曲折且分支不规则的子宫内膜腺体,以及缺乏嗜酸性白细胞向子宫内膜的生理性正常浸润(子宫内膜嗜酸性归巢),这一发现此前未见报道。
本研究结果表明,高剂量的ND会导致雌性大鼠子宫出现形态和生理改变,这些改变与它们的生殖能力受到抑制有关。