Cason Z, Tucci M, England B, Benghuzzi H
University of Mississippi Medical Center, Jackson, MS 39216, USA.
Biomed Sci Instrum. 1999;35:205-10.
The specific objective of this study was to investigate the ultrastructural changes in the female reproductive system exposed to long-term sustained release of medroxyprogesterone acetate (MPA), and MPA plus estrogen (MPA + E). Emphases were given towards the vaginal, endometrial and ovarian changes. The microcrystals of tricalcium-phosphate lysine (TCPL) were prepared by following standard laboratory procedure. Adult female rats (BW 250-300 gm) were randomly divided into three groups (n = 3). Group I animals were implanted with TCPL loaded with MPA (50 mg) plus E (50 mg), and group II animals were implanted with TCPL loaded with MPA (200 mg). Group III animals were left as our intact and unimplanted controls. At the end of 21 days post-implantation, all animals were sacrificed by means of an overdose of Halothane and the reproductive, as well as, the vital organs were collected, weighed, fixed, embedded, sectioned, and stained (H & E) for histopathological evaluations. Vaginal smears were collected prior the implantation to assess the fertility events and subsequently taken on a daily basis for the entire period of the investigation. The data obtained from this study demonstrates the following: (1) TCPL delivery system was capable of releasing MPA, and MPA + E at a sustained level for 21 days, (2) the use of TCPL devices resulted in the cessation of the estrus cycle and that was achieved at the end of 24 hour post-implantation, (3) remarkable physiological changes were observed in animals implanted with MPA, and MPA + E compared to control group animals, (4) regression of the ovarian tissue was observed in all MPA treated animals compared to intact control animals, and (5) histopathological evaluation of the endometrium of animals treated with sustained delivery of MPA, and MPA + E revealed increased stratification, altered polarity, cytoplasmic vacuolation and papillary projections.
本研究的具体目的是调查长期暴露于醋酸甲羟孕酮（MPA）及MPA加雌激素（MPA + E）持续释放环境下雌性生殖系统的超微结构变化。重点关注阴道、子宫内膜和卵巢的变化。按照标准实验室程序制备磷酸三钙赖氨酸（TCPL）微晶。成年雌性大鼠（体重250 - 300克）随机分为三组（n = 3）。第一组动物植入负载MPA（50毫克）加E（50毫克）的TCPL，第二组动物植入负载MPA（200毫克）的TCPL。第三组动物作为完整未植入的对照。植入后21天结束时，所有动物通过过量吸入氟烷处死，收集生殖器官以及重要器官，称重、固定、包埋、切片并进行苏木精和伊红（H & E）染色以进行组织病理学评估。在植入前收集阴道涂片以评估生育事件，并在整个研究期间每天收集。本研究获得的数据表明：（1）TCPL给药系统能够持续21天释放MPA和MPA + E；（2）使用TCPL装置导致发情周期停止，在植入后24小时结束时实现；（3）与对照组动物相比，植入MPA和MPA + E的动物观察到显著的生理变化；（4）与完整对照动物相比，所有接受MPA治疗的动物均观察到卵巢组织退化；（5）对持续释放MPA和MPA + E治疗的动物子宫内膜进行组织病理学评估显示分层增加、极性改变、细胞质空泡化和乳头样突起。
